JEADV
DOI: 10.1111/jdv.13127
ORIGINAL ARTICLE
Anatomoclinical study of 30 cases of sclerosing sweat duct carcinomas (microcystic adnexal carcinoma, syringomatous carcinoma and squamoid eccrine ductal carcinoma) E. Frouin,1,*,† M.D. Vignon-Pennamen,2,3,† B. Balme,4,† B. Cavelier-Balloy,2,5,† U. Zimmermann,3,6,† ,9 B. Cribier10,† N. Ortonne,7,† A. Carlotti,8,† L. Pinquier,2,4,† J. Andre ^pital Jean Bernard, CHU, Poitiers, France Laboratoire d’Anatomie et de Cytologie Pathologiques, Ho ^pital Saint Louis, APHP, Paris, France Service d’Anatomie pathologique, Ho 3 e de la Roquette, 56 rue de la Roquette, Paris, France Centre de Pathologie cutane 4 Laboratoire d’Anatomie pathologique, Centre hospitalier Lyon Sud, Lyon, France 5 Cabinet d’Anatomie pathologique dermatologique, 35 avenue Mathurin Moreau, Paris, France 6 ^pital Ambroise Par Laboratoire d’Anatomie pathologique, Ho e, APHP, Boulogne-Billancourt, France 7 ^pital Henri Mondor, APHP, Cre teil, France D epartement de Pathologie, Ho 8 ^pital Cochin-Tarnier, APHP, Paris, France Service d’Anatomie et de cytologie pathologiques, Ho 9 Centre d’Anatomie pathologique et de cytologie, Avenue du Diamant, Bruxelles, Belgium 10 e, Clinique Dermatologique, Ho ^pital Civil, Strasbourg, France Laboratoire d’Histopathologie cutane *Correspondence: E. Frouin. E-mail: [email protected] 1 2
Abstract Background Microcystic adnexal carcinoma (MAC), syringomatous carcinoma (SC) and “Squamoid eccrine ductal carcinoma” (SEDC) are rare sclerosing adnexal tumours. Objective To understand the histogenesis of these tumours and possible clinical implications. Methods We conducted a retrospective study of 30 cases, 18 MAC, 5 SC and 7 SEDC reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts, and PHLDA1 expressed in adnexal structures. Results There was a strong female predominance, with only five cases occurring in men. Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Two cases of SEDC were found in organ transplant patients. No recurrence or metastases were observed after complete surgery of MAC, or SC (mean follow-up 7.2 years and 4.7 years), whereas one case of SEDC recurred and another could not be fully excised. MAC and SC had similar histological features, except for cysts. In MAC, calcifications, granulomas, connection to follicles, keratin expression pattern, PHLDA1 positivity and K77 negativity indicated a follicular histogenesis, whereas in SC, K77 positivity and keratin expression pattern were consistent with a differentiation towards eccrine apparatus. SEDC was composed of strands centred by ducts and nests with squamous differentiation and displayed K77 ductal positivity in all cases, a finding consistent with an eccrine origin. Conclusion Our study demonstrated that MAC and SC have similar clinical characteristics, although histogenesis differs and show arguments for the individualization of SEDC. Received: 5 January 2015; Accepted: 2 March 2015
Conflict of interest and source of funding The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Introduction Skin adnexal carcinomas are rare neoplasms with an incidence rate of 5.1 per 1 million person-years.1 Microcystic adnexal †
French dermatopathological section of the French Dermatological Society
(SFD). Collaborators from the French dermatopathological section of the French Dermatological Society SFD: Plantier F; Clerici T; Moulonguet I; Moguelet P; Sass U; Le Pelletier F; Truchetet F; Baudin M; Petit T; Lemasson G; Grossin M;.
JEADV 2015, 29, 1978–1994
carcinoma (MAC) and syringomatous carcinoma (SC) are one of the most frequents. Since the first reports,2,3 many names were given to these entities reflecting controversies regarding histogenesis. In 1985, Cooper et al.4 proposed the term “Sclerosing sweat duct carcinoma” (SSDC), and pointed out the similarities between the two entities. These tumours consist of slowly growing and indurated plaques that cannot be differentiated
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1979
from one another. Location seems to differ as SC predominates on the scalp, whereas MAC is located on the middle of the face.5,6 As metastases are very uncommon, Smith et al. and further Pujol et al. proposed the term of “locally aggressive adnexal carcinomas” (LAAC) with variations in histopathological findings.7,8 Recently, Wong et al.9 reported four tumours showing strands centred by ducts and nests with squamous differentiation which they called “squamoid eccrine ductal carcinoma” (SEDC). Since then, other authors emphasized that this tumour may be misdiagnosed as squamous cell carcinomas (SCC). Evolution of SEDC seems to be distinct from those of SCC, as local recurrence rate is high, although metastases are rare.10 Accordingly, a link between MAC and SEDC has been recently evoked.11 To understand the histogenesis of MAC, SC and SEDC and possible clinical implications, we conducted a clinicopathological study of 30 cases, reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts,12 and PHLDA1 (TAG-2) expressed in follicular and eccrine structures.13
Material and methods Twenty members of the Dermatopathology group of the French Society of Dermatology retrieved from their own
collection all cases of eccrine carcinomas diagnosed between 1995 and 2008. All cases were reviewed and classified by the panel. All cases retained followed previously reported histological criteria.2,4,9 Briefly, all tumours were made of deeply invasive basaloid strands with ductal differentiation suggestive of eccrine origin. Tumours with keratinizing cysts were classified as MAC. Those composed of strands without cysts or parakeratotic island, were classified as SC. Tumours showing squamous differentiation, i.e. islands with parakeratotic keratinization were classified as SEDC. Clinical information and follow-up were obtained from dermatologists and general practitioners. We looked for past medical history, especially malignancy (location, duration, radiation and chemotherapy). We studied the type of treatment (size of margins, number of procedures needed, Mohs surgery), number of recurrences before and after treatment of the lesion studied, and follow-up. Histological analyses were performed on routinely formalin fixed tissues except for a few cases fixed with Bouin solution; 36 samples (24 excisions and 12 biopsies), were examined. We obtained more than one sample of the tumour in five patients.
Table 1 Immunohistochemistry material and methods Antibody name
Clone (origin)
Type of antibody
Dilution
Antigen retrieval
Time of incubation
AE1/AE3
AE1AE3 (Dako)
Monoclonal (mouse)
1/50
Citrate
20 min
KL1
KL1 (Immunotech)
Monoclonal (mouse)
None
Citrate
20 min
K1
anti-human K1.1-gp (Langbein)
Polyclonal (guinea pig)
1/1000
EDTA
24 h
K5
Anti-human CK5.2-gp (Langbein)
Polyclonal (guinea pig)
1/1000
EDTA & Trypsine
24 h
K6
Anti-human KA12 (Langbein)
Monoclonal (mouse)
1/100
EDTA
24 h
K7
OV-TL 12/30 (Dako)
Monoclonal (mouse)
1/25
Citrate
20 min
K8
35bH11 (Dako)
Monoclonal (mouse)
1/50
Citrate & Trypsine
20 min
K10
Anti-human DE-K10 (Langbein)
Monoclonal (mouse)
1/1000
EDTA
24 h
K14
CK14.2 (Langbein)
Polyclonal (guinea pig)
1/1000
Citrate & Trypsine
24 h
K16
CK16.1 (Langbein)
Monoclonal (mouse)
1/200
EDTA
24 h
K17
E3 (Dako)
Monoclonal (mouse)
1/100
Citrate & Proteinase K
20 min
K18
DC10 (Dako)
Monoclonal (mouse)
1/10
Citrate & Proteinase K
20 min
K19
RCK108 (Dako)
Monoclonal (mouse)
1/50
Citrate & Trypsine
20 min
K77
Anti-human CKT5N.2-gp (Langbein)
Polyclonal, (guinea pig)
1/500
EDTA
24 h
PHLDA1
RN-6E2 (Santa-Cruz)
Monoclonal, (mouse)
1/25
EDTA
20 min
ACE
12.140.10 (Novocastra)
Monoclonal (mouse)
None
Citrate
20 min
EMA
E29 (Dako)
Monoclonal (mouse)
1/100
Citrate
20 min
PS100
NCL-L-S100p (Novocastra)
Polyclonal (rabbit)
1/5
Citrate
20 min
Actin
1A4 (Dako)
Monoclonal (mouse)
1/200
EDTA
45 min
GCDFP15
D6 (Covance)
Monoclonal (mouse)
1/100
EDTA
20 min
Ber-EP4
Ber-EP4 (Dako)
Monoclonal (mouse)
1/100
Citrate
20 min
P63
4A4 (Santa Cruz)
Monoclonal (mouse)
1/25
EDTA
20 min
Ki-67
MIB-1 (Dako)
Monoclonal (mouse)
1/20
EDTA
20 min
The table resume the characteristics of each antibody (Ab) used in this study. Sections were heated for antigen retrieval in sodium citrate buffer pH 6.0 (Citrate) or in EDTA pH7.8 (EDTA) followed by trypsinization for 3 min at 37°C (Trypsine) or proteinase K digestion for 5 min (Proteinase K). Some antibodies, especially keratins, were kindly supplied by Lutz Langbein, Heidelberg, Germany (Langbein).
JEADV 2015, 29, 1978–1994
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
MAC
8
MAC
MAC
7
12
MAC
6
MAC
MAC
5
11
MAC
4
MAC
MAC
3
10
MAC
2
MAC
MAC
1
9
Diagnosis
Case
F
F
F
F
F
F
F
F
F
F
F
F
Sex
52
45
56
88
41
46
73
24
75
65
68
73
Age (years)
CLL (untreated for 12 years)
Cervix cancer treated by surgery and curietherapy 4 years before
Past medical history
Scalp
Eyebrow (left)
Nose (left)
Cheek (right)
Back
Eyebrow (left)
Cheek
Lip
Nose (left)
Cheek (right)
Scalp
Nose
Location of tumour
6
1
1 (recurrent tumour)
4 (recurrent tumour)
1,3
Unknown
0,2
3
3
1
1,5 (recurrent tumour)
10
Duration of tumour prior first treatment (years)
Table 2 Clinical characteristics of the 30 cases of sclerosing sweet ducts carcinomas
3
1.2
0.3
Unknown
0.5
1
0.5
0.4
Large (check, nose)
2
3.5
2
Tumour size (cm)
Painful indurated erythematous plaque with scales
Nodule
Sclerodermoid plaque with telangiectasia
Indurated plaque
Bluish indurated nodule
Nodule
Plaque
Indurated and ulcerated nodule
Nodules under indurated plaque
Ulcerated and crusted nodule
Ulcerated nodule
Erythematous indurated plaque
Clinical description
Conventional surgery (2 procedures; large margins) Conventional surgery followed by slow Mohs surgery (5 procedures)
dTE
Unknown
Conventional surgery (1 procedure; large margins)
BCC
11.2 (A)
5.9 (A)
5.5 (A)
4.5 (DND)
6.6 (A)
Conventional surgery (2 procedures; 2 cm margin)
Conventional surgery (2 procedures; 1 cm margin)
6.5 (A)
5.4 (A)
5.7 (A)
11.2 (A)
12.9 (A)
4 (A)
2.9 (A)
Follow-up (year and status)
Conventional surgery (3 procedures; margin unknown)
Conventional surgery (2 procedures; 0.5 cm margin)
Conventional surgery (4 procedures; 2 cm margin)
Conventional surgery (2 procedures; large margins)
Conventional surgery (1 procedure; 3 cm margin)
Mohs surgery (3 procedures; large margins)
Conventional surgery (2 procedures; 1 cm margin)
Surgical treatment
BCC
BCC, melanoma, granuloma annulare, morphea
Unknown
BCC
Unknown
Sarco€ıdosis
Unknown
BCC, dTE
Unknown
Clinical diagnosis evoked
1980
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
SC
SC
19
23
MAC
18
SC
MAC
17
22
MAC
16
SC
MAC
15
21
MAC
14
SC
MAC
13
20
Diagnosis
Case
Table 2 Continued
F
F
F
M
F
M
M
M
F
F
F
Sex
52
67
36
27
53
63
43
55
59
52
30
Age (years)
4 month pregnant
Past medical history
Cheek (left)
Lower eyelid (left)
Cheek (left)
Cheek (left)
Nasolabial (left)
Forehead
Eyebrow (right)
Eyebrow (right)
Arm (left)
Scalp
Thigh (left)
Location of tumour
Unknown
0.2
Recent lesion
Unknown
Large
4
0.5
3.9
3.5
0.3
3.5
1.5
0.4
Tumour size (cm)
Unknown
1
25 (recurrent tumour)
1
0,4
10
2
15
Unknown
Duration of tumour prior first treatment (years)
Indurated plaque
Nodule
Indurated plaque
Indurated plaque
Nodule on indurated plaque
Indurated and ulcerated plaque
Indurated plaque
Indurated plaque
Painful indurated plaque
Plaque
Indurated plaque
Clinical description
BCC
BCC
Unknown
DFPS
Slow Mohs surgery
Conventional surgery (1 procedure; 0.5 cm margin)
Conventional surgery (1 procedure; 1.5 cm margin)
Conventional surgery (1 procedure; 1 cm margin) and lymph node excision (negative)
Conventional surgery (3 procedures; 1 cm margin)
Unknown
3.3 (A)
5.5 (A)
4 (A)
4.8 (A)
5.9 (A)
9.5 (A) Conventional surgery (2 procedures; 1 cm margin)
BCC
Lymphoma, cutaneous mucinosis
8.5 (A)
2 (A)
10.6 (A)
12.4 (A)
Follow-up (year and status)
4.4 (A)
Conventional surgery followed by slow Mohs surgery (1 procedure) and Lymph node excision (negative)
Conventional surgery (1 procedure; 3 cm margin) and Lymph node excision (negative)
Conventional surgery (1 procedure; 0.3 cm margin)
Conventional surgery (3 procedures; 2 cm margin)
Surgical treatment
Conventional surgery (2 procedures; 1 cm margin)
sBCC
DFSP
BCC
Dermatofibroma
Clinical diagnosis evoked
Sclerosing sweat duct carcinomas 1981
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
SEDC
SEDC
27
28
F
F
M
F
F
F
F
Sex
96
76
80
71
91
81
74
Age (years)
SSM Breast cancer (radiation, surgery)
Bowen disease, BCC, SCC Liver transplantation 11 years before (cyclosporin)
Bowen disease, BCC, SSM
Kidney transplantation 15 years before (cyclosporin and corticosteroid) SCC 11 years before
Past medical history
Cheek (right)
Cheek (right)
0.4
1
0.5
4.0
Unknown
7.8
0.5
Unknown
Internal canthus (right)
Cheek (right)
Unknown
0.3
Unknown
1.5
Tumour size (cm)
Nose (left)
Unknown
2 (recurrent tumour)
Nose
Forehead
Duration of tumour prior first treatment (years)
Location of tumour
Unknown
Nodule
Induration with scales
Erythematous plaque with scales
Indurated and ulcerated nodule
Unknown
Nodule
Clinical description
SCC
BCC
Conventional surgery (4 cm margin) followed by slow Mohs surgery (5 procedures) with incomplete margins
Large conventional surgery
Conventional surgery (2 procedures; margin unknown)
2.7 (recurrence; AWD)
4.5 (A)
3.7 (A)
7.7 (A) Conventional surgery (1 procedure; 1 cm margin) Switch from cyclosporin to tacrolimus Bowen disease, SCC, BCC
SCC
5.7 (A) Conventional surgery (1 procedure; margin unknown)
Unknown
13 (A)
3.5 (DOD)
Follow-up (year and status)
Conventional surgery (2 procedures; 2 cm margin)
Large conventional surgery (5 procedures) with enucleation, and nose amputation followed by radiation (65 Gy) Decreased cyclosporin and switch corticosteroid to sirolimus
Surgical treatment
Unknown
SCC
Clinical diagnosis evoked
A, alive without disease; AWD, alive with disease; BCC, basal cell carcinoma; CLL, chronic lymphocytic leukaemia; DFPS, dermatofibrosarcoma protuberans; DND, dead not of disease; DOD, dead of disease; dTE, desmoplastic trichoepithelioma; F, Female; M, male; MAC, microcystic adnexal carcinoma; SC, syringomatous carcinoma; SCC, squamous cell carcinoma; SEDC, Squamoid eccrine ductal carcinoma; sBCC, sclerodermiform basal cell carcinoma; SSM, superficial spreading melanoma.
SEDC
SEDC
26
30
SEDC
25
SEDC
SEDC
24
29
Diagnosis
Case
Table 2 Continued
1982
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1983
Imunohistochemistry
Antibody dilution and antigen retrieval techniques are summarized in Table 1. The labelled streptavidin biotin (LSAB) immunostaining kit (Dako) with biotinylated anti-guinea pig, anti-mouse or anti-rabbit IgG was used for visualization of bound antibodies. Haematoxylin was used for counterstaining.
Results One hundred and four tumours were reviewed and only 30 cases were retained for the present study, 18 were classified as MAC, five as SC and seven as SEDC. Other cases were eliminated because of diagnostic errors (other types of adnexal tumours, especially of follicular histogenesis), absence of ductal structures, features suggestive of other types of eccrine carcinomas. Clinical and epidemiological data
There was a strong female predominance, with only five cases occurring in men and very similar sex-ratio in the three groups (Tables 2 and 3). Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). There were two young patients, one with MAC (24 years) and one with SC (27 years), whereas the older patient was 88 years and had MAC. The vast majority of tumours were located on the face (80%). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Duration before excision was long in MAC and SC, reaching 15 years in a patient with MAC and 25 years in another with SC. Three cases of MAC and two of SC were recurrent tumours.
A past medical history of skin cancers was found in four patients with SEDC. Two patients had had liver or renal transplant 10 and 15 years before the diagnosis of SEDC, whereas a patient was 4 months pregnant when MAC was diagnosed. None of our patients had radiotherapy at the site of sclerosing carcinoma or systemic chemotherapy before the diagnosis. The clinical description MAC was a plaque in 10 cases, indurated in nine cases, or a nodule in eight cases (44%) indurated in three. Pain was present only in two cases. The clinical aspect of SCs was a painless indurated plaque in four cases (80%) (Fig. 1), whereas SEDC consisted of painless nodule in two cases, erythematous plaque in 1 and “induration” in 1. The diagnosis of a sclerosing sweat duct carcinoma was never evoked by clinicians. Patients with MAC were all treated by surgery with healthy margins (mean 1.5 cm) in 12 cases; “large” margins were done in six cases. One to five surgical procedures were necessary to obtain free margins. In two patients, slow Mohs surgery followed conventional surgery. Patients with SC were all treated by surgery with healthy margins (mean 1 cm), one of them by slow Mohs surgery. One to three surgical procedures were necessary. All patients with SEDC had surgery, one of them with slow Mohs. One to five surgical procedures were needed (mean margins 2.3 cm). In one case, large excision with enucleation and nose amputation was required, followed by radiation therapy. Two patients with MAC had negative sentinel lymph node excision, and one patient with SC had a negative complete lymph node excision. No recurrence or metastases were observed during follow-up (mean 7.2 years in MAC and mean 4.7 years in SC). In patients
Table 3 Synthesis of epidemiological and clinical characteristics of the 30 cases of sclerosing sweet ducts carcinomas MAC
SC
SEDC
Number of cases
18
5
7
Sex (M : F)
3 : 15
1:4
1:6
Mean age (range)
56 (24–88)
47 (27–67)
81 (71–96)
Location of the lesions Face, n (%)
12 (67)
5 (100)
7 (100)
Lips, n (%)
1 (6)
1 (20)
0 (0)
Nose, n (%)
3 (17)
0 (0)
2 (29)
Cheek, n (%)
3 (17)
3 (60)
3 (43)
Forehead, n (%)
1 (6)
0 (0)
1 (14)
Ocular area, n (%)
4 (22)
1 (20)
1 (14)
Scalp, n (%)
3 (17)
0 (0)
0 (0)
Trunk, n (%)
1 (6)
0 (0)
0 (0)
Limbs, n (%)
2 (11)
0 (0)
0 (0)
Mean time duration (range)
3.7 years (0.2–15)
13 years (1–25)
0.8 years (0–2)
Size of the lesion (range)
1.7 cm (0.3–3.9)
1.5 (0.2–4)
3.4 cm (0.5–7.8)
Mean number of surgical procedures (range)
2.2 (1–5)
1.5 (1–3)
2.3 (1–5)
Mean size margin (range)
1.6 cm (0.3–3)
1 cm (0.5–1.5)
2.3 cm (1–4)
Mean follow-up (range)
7.2 years (2–12.9)
4.7 years (3.3–5.9)
5.8 years (2.7–13)
Recurrence or metastasis
None
None
2 recurrences
JEADV 2015, 29, 1978–1994
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
+
Basal cells
+
+
+
+
Poroid cells
Luminal cells of acrosyringium
+/
+/
+ (i)
+
+
+
Bulge
Follicular germinative cells
Outer sheath
+/
+
+
+/
+
+/
+/
+
+
+
K8
+/
+/
+ (i)
+ (i)
+/
+
+††
+
K10
+
+
+
+
+
+
+ (o)
+ (o)
+
+
+
+
+
+/ †
K14
+
+ (i)
+ (i)
+
+
+*
K16
+
+ (i)
+ (i)
+/
+
+*
K17
+/
+/
+
+
+
+
+
+
K18
+/
+
+
+
K19
+
+
K77
+ +
+
+
PHLDA1
+
+
BerEP4
*K6, K16, K17 and EMA were only positive in the suprabasal cells of reactive epidermis. †K14 was slightly positive in suprabasal epidermis in some lesions. ‡PS100 was positive in melanocytes and in Langerhans cells. §P63 was positive in basal and suprabasal cells but neither in inner nor in superficial cells of follicles and epidermis. ¶EMA highlighted the luminal cell pole of sweat ductular and secretory cells. **ACE highlighted the luminal cell pole of some sweat secretory cells. ††K10 was positive in luminal cells in the superficial part of the eccrine ducts. ‡‡GCDFP15 was slightly positive in the cytoplasm of luminal sweat duct cells. §§K7 was positive predominantly in outer sebocytes. +, positive; , negative; +/ , occasionally positive cells or inconstant positivity within lesions; i, only inner cells positive; o, only outer cells positive.
+/ §§
+
+
Sebaceous ducts
+
+ (i)
+ (i)
+/
Sebocytes
+
+
+
+
+ (o)
+
K7
+
+ (i)
+
+
*
K6
Undifferentiated cells
Sebaceous gland
Matrical cells
+
+ (i)
+
Isthmus
Inner sheath
+ (i)
+
Infundibulum
+ (o)
+
+
Luminal cells of ducts
+ (i)
+
+
Cuticular cells of ducts
Hair follicles
+
+
+
K5
+
+
+
K1
Myoepithelial cells
+
+
Kl1
Secretory cells
Eccrine sweat glands
+
Suprabasal cells
Epidermis
AE1/ AE3
Table 4 Immunohistochemical findings for all tested antibodies in normal skin, exception of Ki-67
+
+
+¶
+¶
+¶
+*
EMA
+
+
+**
ACE
+‡
+‡
+‡
+‡
_
_
_
+
+‡
+‡
S100
+
Actin
+‡‡
+‡‡
+
GCDFP15
+
+
+
+
+
+
+§
+§
+/
+
+
+
+§
P63
1984
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1985
with SEDC, one developed recurrence after 32 months and another had incomplete excision but none had metastases. This last patient died 42 months after diagnosis because of slowly growing, eroded, and bleeding tumour. In the others, no recurrence or metastasis were observed during follow-up (mean 5.8 years). Histopathological findings MAC (n = 18) All cases contained small cysts with a granular layer, centred by “glassy” or laminated keratin (Figs 2 and 3).
Strands predominated over cysts (12 cases) and were centred by ducts (16 cases). Tadpole structures were seen in eight cases (Fig. 3). Apocrine differentiation was present in two tumours (Fig. 3). Clear cells sometimes resembling sebaceous cells were seen in 11 cases (Fig. 3). Mitotic activity was low (1 per 10 high-power fields), without atypical mitoses nor cellular atypia. Tumour nests were connected to the follicles in seven cases. Foreign body type granuloma was present in 11 cases and calcification in three (Fig. 3). All tumours were deeply invasive (fat tissue n = 6, muscle n = 7, structures underlying muscles n = 3), with perineural invasion in seven cases (Fig. 3). SC (n = 5) All cases were made only of strands limited by smooth border, without cysts or nests (Fig. 4). Tadpole structures and ducts were always present (Fig. 4), without apocrine differentiation. Clear cells were present in two cases. There was no connection to the epidermis or follicles, but extension to fat tissue (n = 4), perineural invasion (n = 2). Mitoses were rare (< 1 per 10 HPF). No inflammation was noticed.
Figure 1 Sclerotic plaque of the left cheek of a 28 year-old man (Syringomatous carcinoma).
(a)
Figure 2 Silhouette of microcystic adnexal carcinomas. (a) MAC made predominantly of cysts with a few strands invading of the deep of the lip (HES, 9 1). (b) Deep strands surrounded by sclerotic stroma, with epidermal cysts in the upper part (HE, 9 4). (c) Deep dilated ducts with smooth borders centred by an eosinophilic material (HE, 9 4). (d) MAC of the scalp, composed of epidermal cysts connected to the epidermis associated with strands centred by ducts. (HE, 9 1).
JEADV 2015, 29, 1978–1994
SEDC (n = 7) Tumours were made of nests and strands with angulous borders (Fig. 5), and cysts lined by a granulous layer and centred by paraketatotic, laminated or glassy keratin (Fig. 5). Clear cells were noted in 2. Ducts were always present in the superficial nests and also in the deep strands (four cases), without signs of apocrine differentiation. All but one tumours were connected to the epidermis (Fig. 5). Strands invaded the deep dermis (n = 2 cases), fat tissue (n = 2), underlying muscle (n = 2) and cartilage (n = 1), with
(b)
(c)
(d)
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1986
(a)
(d)
(b)
(c)
(e)
(h)
(f)
(g)
(i)
Figure 3 Histological features of MAC. (a) Cysts centred by glassy keratin (HE, 9 10). (b) Cysts centred by keratin reminiscent of epidermal cysts (HE, 9 10). (c) Clear cells within islands centred by cysts (HE, 20). (d) Tumour nests and cysts occasionally calcified (HE, 9 20). (e) Inflammatory granulomatous reaction (HES, 9 10). (f) Clear cells resembling sebaceous cells – (HES, 9 20). (g) Perineural invasion in deep adipose tissue (HES, 9 20). (h) Ducts with features suggestive of apocrine differentiation (HE, 9 20). (i) Collagenic stroma in deep strands (HE, 9 10).
perineural (n = 4) and perivascular invasion (n = 4) (Fig. 5). Nuclear atypia was seen in one tumour (Fig. 5), and mitoses in two (2–5 per HPF) (Fig. 5). Immunohistochemical findings
Tables 4 and 5 show an overview of immunohistochemical results. MAC A sequential pattern keratine expression was observed.
All cases strongly expressed K14. K5, K1, K10, K6 and K16 were strongly expressed in almost all cases, preferentially in the upper parts, and lightly in strands (Fig. 6). K17 labelled cysts, nests and strands, but never ducts, whereas luminal cells of ducts expressed K7. K8, K18 and K19 were expressed strongly and diffusely in
JEADV 2015, 29, 1978–1994
deep strands, in luminal cells of ducts, but also in outer cell rows of cysts (Fig. 6). K77 was expressed in only two cases, mainly in ducts (Fig. 6). GCDFP15 and Ber-EP4 were constantly negative. PHLDA1 staining displayed two different patterns, moderate positivity in upper nests and diffuse expression in strands and ducts (Fig. 6). Mean proliferation index (Ki-67) was 3.8% (range 1–15%). SC K5 and K14 were diffusely expressed. K1 and K10 were positive in only one case. K6 and K16 labelled ducts, whereas strands were positive only for K6. K17 was expressed only in strands. Certain ducts expressed K7, whereas ducts and strands were constantly positive with K8, K18 and K19. K77 was expressed in ducts (Fig. 6).
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1987
(a)
(c)
(b)
(d)
(e)
Figure 4 Histopthological findings in syringomatous carcinoma (SC). (a) Deeply invasive strands within collagenic and mucinous stroma (HE, 9 2). (b–c), SC composed of round well-formed ducts and few strands (HE, 9 4 and HE, 9 10 respectively). (d–e), Case A at higher magnification showing tadpole appearance of ducts lined by one to two cell rows and neural invasion (HE, 9 20).
Ber-EP4 and GCDFP-15 were always negative. PHLDA1 was strongly positive in 2/3 cases in strands and ducts (Fig. 6). Mean Ki-67 was lower than 1%. SEDC K14 was diffusely positive, whereas K5 was slightly posi-
tive in basal layers of nests/cysts, strongly in strands. K1 and K10 predominated in superficial nests and cysts (Fig. 7). Keratin 6 and 16 were expressed in inner portions of epidermoid nests, whereas only K6 strongly labelled deep strands (Fig. 7). K17 had a similar diffuse expression as K6, but also strongly labelled ducts (Fig. 7). K8, K18 and K19 were positive in strands and ducts (Fig. 7), whereas K7 was positive in ducts of two cases. Keratin 77 was always positive in ducts (Fig. 7). Ber-EP4 and GCDFP-15 were constantly negative. PHLDA1 was positive mainly in the deepest parts of strands, slightly positive in nests (Fig. 7). Mean Ki67 was 4% (range 1–15%).
Discussion As many cases of MAC were reported under the name of SC and conversely, with incomplete description, the review of literature is very difficult. Even recent studies were published without detailed pathological review.1,14,15 Our study of SSDC selected by a panel of dermatopathologists was performed to determine
JEADV 2015, 29, 1978–1994
if subgroups can be identified on the basis of pathology/immunohistochemistry and if they are relevant for clinical management. Our study pointed out many clinical similarities between MAC and SC, as both occur mainly on the cephalic extremity of adults in their 50s. It has been widely reported that SC predominates on the scalp and presents as a slowly enlarging alopecic plaque, whereas MAC presents as a slowly growing plaque or nodule of the nasolabial fold or periocular area. We found similar anatomical distribution and clinical presentation in both groups, including uncommon extra-cephalic cases. Pain due to perineural involvement is regarded as a possible symptoms but was rarely observed in our experience. Lack of pain can account for the long duration before treatment. Hansen et al.16 noticed 14% of MAC present for more than 5 years and some up to 25 years. Both MAC and SC can measure up to 10 cm,6,17 which explains difficult surgical management. Surgery is the best treatment, ideally Mohs surgery which allows a lower rate of recurrence.18 After a mean follow-up of 4.7 and 7.2 years, respectively, none of our patients developed recurrences after complete surgery. Sentinel and prophylactic large lymph node excisions were performed in three of our patients and all were
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1988
(a)
(c)
(f)
(b)
(d)
(g)
(e)
(h)
Figure 5 Histological silhouettes and features of SEDC. Epidermoid nests centred by ducts and strands invading the muscle. Tumour covered by hyperplasic and hyperkeratotic epidermis (a HES, 9 1; b HES, 9 1). (a–b), Connection to epidermis, and ductal pattern (a, HES, 9 10) or epidermoid pattern (b, HE, 9 10). (c) Epidermoid nest centred by a duct (HES, 9 20). (d–e), Ducts showing typical cribriform pattern (d HES, 9 20; e HES, 9 10). Note nuclear atypia in a cell lining cribriform duct (d). (f) Parakeratotic keratinization in deepest parts (f HE, 9 10). (h) Perivascular invasion (HE, 9 4). (i) Mitosis within epidermoid islands (HE, 9 20).
negative. Lymph node or visceral metastases of MAC or SC are rare and prophylactic lymph node excision should not be performed. Finally, our study confirms that the prognosis of MAC and SC is good, as metastases are rare, but local invasion might be severe and needs extensive surgery to avoid recurrences. We observed a majority of common histopathological features in MAC and SC, except for cysts which are absent by definition
JEADV 2015, 29, 1978–1994
in SC. Cysts might be overlooked if step sections are not performed or in small biopsies. Another classic difference is the abundance of ducts in SC, whereas they can be sparse in MAC, but we observed ducts in all our cases of MAC. The histogenesis of MAC remains controversial, whereas SC is generally believed to belong to eccrine tumours. First, MAC was considered as an eccrine tumour, because of similarities with SC in its deepest portions. Epidermal cysts, foci of sebaceous differ-
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
10/11 (o)
10/11 (o)
0/12
0/11
12/12 (o)
0/11
K18
K19
K77
Ber-EP4
PHLDA1
ACE
5/5 (o)
0/5
2/11
8/11
0/11
0/11
0/12
0/11
2/12
8/11 (o)
10/11 (o)
11/11
8/11 (i)
11/11
6/11 (i)
10/11 (o)
0/11
9/11 (i)
6/11 (o)
2/11 (i)
11/11 (i)
5/5
0/5
0/11
8/11
7/11
0/11
12/12
0/11
0/12
10/11
11/11
11/11
1/11
11/11
2/11 (i)
11/11
0/11
5/11 (i)
9/11
0/11
11/11 (i)
11/11
Strands
5/5 (o)
0/5
0/11
0/11
7/11
9/11
12/12
0/11
2/12
10/11
11/11
0/11
3/11 (i)
11/11
2/11 (i)
11/11
7/11
3/11 (i)
5/11
0/11
11/11 (i)
11/11
Ducts
1/1
0/1
0/3
1/3
2/3
0/3
2/3†
0/3
0/5
0/3
0/3
0/3
0/3
3/3
0/3
0/3
0/3
0/3
1/3 (o)
0/3
0/1
3/3
1/1
0/1
1/3
1/3
2/3
0/3
2/3†
0/3
1/5 (i)
2/3
3/3
2/3
0/3
3/3
1/3
3/3
0/3
1/3
2/3
1/3
1/1
3/3
Strands
0/1
0/1
0/3
0/3
2/3
2/3
2/3†
0/3
4/5
2/3
3/3
0/3
1/3
3/3
1/3
3/3
1/3
3/3
2/3
1/3
0/1
3/3
Ducts
2/2
0/2
0/6
6/6
4/6
0/6
4/7 (o)
0/6
0/7
0/6
2/6
3/6
6/6 (i)
6/6
6/6 (i)
1/6
0/6
6/6 (i)
6/6
6/6 (i)
6/6 (i)
6/6
Islands and nests
SEDC (n = 6*) Cysts
2/2
0/2
0/6
6/6
4/6
0/6
0/7
0/6
0/7
0/6
0/6
3/6
6/6 (i)
6/6
6/6 (i)
0/6
0/6
6/6 (i)
0/6
6/6 (i)
6/6 (i)
6/6
Strands
2/2
0/2
1/6
0/6
6/6
0/6
4/7
0/6
1/7 (i)
2/6
4/6
3/6
2/6
6/6
6/6
2/6
2/6 (i)
6/6
6/6
0/6
1/6
6/6
Ducts
0/2
0/2
0/6
0/6
6/6
4/6‡
0/7
0/6
7/7
2/6
3/6
6/6
1/6
6/6
6/6
2/6
2/6
4/6
0/6
0/6
1/6
6/6
*For one case of MAC, SC and SEDC each only K77 and PHLDA1 were tested, whereas for five cases of MAC, one case of SC, and two cases of SEDC GCDFP15 and P63 were tested in supplement. †PHLDA1 has been evaluated only in three SC. ‡ACE was positive only in ducts within epidermoid islands and aggregates, but not in ducts within strands. It labelled strongly material within ducts and only slightly luminal cells. i, inner cells of the islands, nodules, nests, strands, cysts; o, outer cells of islands, nodules, nests, strands, cysts.
5/5
11/11
K17
P63
3/11 (i)
K16
0/5
11/11
K14
GCDFP-15
4/11 (i)
K10
0/11
10/11 (o)
K8
Actine
0/11
K7
8/11
9/11 (i)
K6
S100
7/11 (o)
K5
3/11
1/11 (i)
K1
EMA
11/11 (i)
KL1
11/11
Cysts
Islands and nests
11/11
Islands and nests
AE1/AE3
SC (n = 3*)
MAC (n = 11*)
Table 5 Immunohistochemical findings in 12 cases of Microcystic adnexal carcinoma (MAC), five cases of Syringomatous carcinoma (SC) and seven cases of Squamoid eccrine ductal carcinoma (SEDC)
Sclerosing sweat duct carcinomas 1989
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
85
86
54
53
53
75
Wong et al.9
Wong et al.9
Herrero (1998)31
Kim (2005)
Chhibber (2007)33
Wasserman (2007)34
Kavand and Cassarino11
Terushkin et al.10
Sidiropoulos et al.30*
Pusiol (2011)35
Jung et al.28
Kim et al.29
Clark (2013)36
Wang et al.27
2
3
4
5
6
7
8
9
10
11
12
13
14
15
W
M
M
M
Progressive swelling, erythema and tenderness surrounding an exophytic tumour
Indurated plaque
Slowly growing reddish solitary nodule
Itchy, ulcerated and growing nodule
Slowly growing nodule
Mass
Solitary dermal nodule
Slowly growing nodulo-cystic lesion
Perly telangiectatic plaque with rolled border and central crust
Scabby nodule
Asymptomatic, slow growing reddish coloured eroded nodule
NA
Solitary dermal nodule
Solitary dermal nodule
Solitary dermal nodule
Clinical presentation
16 NA
Left index
26
26
12
NA
27
NA
9
NA
25
20
25
25
25
Size (mm)
Left clavicle
Scalp
Right occiput
Right tibia
Chest
Left Cheek
Great toe
Supra-sternal area
Left forearm
Right side of neck
Right knee
Axilla
Dorsum of hand
Left ear
Location
NA
NA
NA
NA
> 10 years
5.5 months
NA
NA
NA
NA
Ganglion cyst
NA
NA
Keloid or SCC
NA
NA
NA
NA
Clinical diagnosis
10 years
1 year
NA
1 year
3.5 years
1 yr
Several months
4 years
10 years
2 years
2 years
2 years
Duration before diagnosis
N
N
N
N
N
N
N
N
N
Y (3 times because of shave biopsies)
N
NA
N
N
N
Recurrence before diagnosis of SEDC
SCC
N
NA
N
N
SEC
NA
SEDC
N
SCC (on shave excision)
SCC
NA
NA
NA
SEDC
First histopathological diagnosis (if different)
*The third case reported by Sidiropoulos et al. as syringoid eccrine carcinoma displayed keratinization and follow criteria of SEDC. Y, Yes, N, No, NA, not available, SCC, squamous cell carcinoma, SEC, syringoid eccrine carcinoma.
91
W
60-64
W
M
W
61
63
M
M
W
M
W
M
M
Sex
68
90
30
41
81
Wong et al.9
1
32
Age (years)
Reference
Case
Table 6 Clinical and therapeutic findings of cases of SEDC previously reported
Y (multiple systemic metastases)
N
Y (lymph node)
Y (lymph node)
NA
N
N
N
N (after sentinel lymph node biopsy)
NA
N
N
N
N
N
Lymph node or systemic metastasis
12 2
Amputation
24
5
NA
NA
10
8
12
5
14
NA
5
3
NA
Follow-up (month)
MMS
Conventional excision
Conventional excision
Conventional excision
Conventional excision
MMS
Amputation
Conventional excision
Excisional biopsy
MMS
NA
Conventional excision
Conventional excision
Conventional excision
Treatment
Y (after 2 months with lymph node and multiple systemic metastases)
N
Y (after 3 months with locally and lymph node metastasis)
Y (lymph node metastasis)
N
NA
N
N
N
N
N
NA
NA
NA
3 times (since clear margins)
Recurrence
1990
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
(a)
1991
(b)
(d)
(f)
(c)
(e)
(g)
Figure 6 Immunohistochemical findings in MAC (a-e) and SC (f-g). (a) K77 labels normal eccrine ducts but not tumoural strands in MAC (a K77, 9 10). (b) K77 strongly expressed in inner cells of certain ducts, and slightly in inner cells of cysts in MAC (K77, 9 10). (c) K8 expression restricted to outer cells of islands and cysts but diffused in strands in MAC (K8, 9 10). (d) PHLDA1 pattern with strong expression in strands, and cells lining ducts, moderate in islands containing cysts in MAC (PHLDA1, 9 4). (e) In contrast to K8, K16-labelled inner cells of cysts in MAC (K16, 9 10). (f) K77 expression in luminal cells of ducts in SC (K77, 9 10). (g) PHLDA1 strongly positive in luminal cells of ducts in SC (PHLDA1, 9 10).
entiation and immunohistochemical patterns are more consistent with a follicular origin, but ducts are difficult to explain. The apocrine nature of such ducts has never been demonstrated. Calcifications were found in three of our cases and are wellknown features of many pilar tumours, whereas they are rarer in sweat gland tumours.19,20,21,22 Another argument in favour of a follicular origin is the connexion to follicles seen in near 40% of our cases of MAC. Many immunohistological studies were carried out to clarify histogenesis and for the purpose of differential diagnosis, especially with BCC or desmoplastic trichoepithelioma (dTE). BerEP4 is a marker of normal eccrine secretory and follicular germinative cells, but unlike BCCs, MAC do not express Ber-EP4.23,24 PHLDA1 is a new follicular marker which labels the stem cell of follicular bulge and also eccrine coils. It does not help to differentiate dTE from MAC.24 The keratin expression pattern we observed in MAC is similar to what was previously reported in dTE, suggesting a common bulge-derived origin.25 The absence
JEADV 2015, 29, 1978–1994
of K77 expression (believed to be specific of eccrine excretory ducts)26 in the majority of our cases is a further argument against the eccrine histogenesis. In rare cases (two in this series), expression of K77 in ducts of otherwise classic cases of MAC might be interpreted as a double follicular/eccrine differentiation. In SC, immunohistochemical findings are more consistent with a differentiation towards eccrine apparatus. K77 positivity favours this hypothesis. Langbein et al.12 published the detailed keratin expression pattern of syringomas showing clear-cut eccrine origin. This pattern is similar to what we observed in SC, except for the absence of K8/K18 in syringomas. SC could therefore arise from cells of the secretory and lower excretory portions of the eccrine apparatus. Less than 20 cases of SEDC were reported to date. The term of “squamoid eccrine ductal carcinoma” was proposed by Wong TYet al.,9 for lesions with eccrine ductal differentiation associated with a prominent squamous component. This first short
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1992
(a)
(b)
(c)
(e)
(d)
(f)
(g)
(h)
Figure 7 Immunohistochemical findings in SEDC. (a–b) K77 labels strongly ducts, (a, 9 4 and b, 9 10). (c) PHLDA1 expressed slightly in superficial islands, predominantly in outer cells. Note the strong positivity in a follicular structure (PHLDA1, 9 10). (d) K10 expression in epidermal suprabasal cells and in tumoural inner cells (K10, 9 4). (e) K16 expressed in epidermoid structures, (e, 9 10). (f) CEA expressed in luminal cells of ducts, emphasizing the ductular component of SEDC (CEA, 9 10). (g) K8 diffusely expressed in deep strands (K8, 9 4). (h) K17 positive in inner cells of islands, and ducts (K17, 9 4).
series concerned patients in their 80s, but patients might be younger.9 Since the review of Terushkin et al. in 2009, we found eight new cases in the literature, including one reported by Sidiropoulos et al. under the name of “syringoid eccrine carcinoma”, but that displayed all criteria of SEDC (see updated review in Table 6).10–11,27–36 Mean age was 66.1 years, (30–91), with a slight male predominance (sex ratio 1.5). In our patients, lesions were exclusively located on head and neck, but previous reports concerned mostly tumours outside the cephalic extremity. Time duration before diagnosis ranged from months to 10 years. Clinically, lesions were described as nodules or plaques with possible erosion or crusting. To the best of our knowledge, the association with organ transplant or immunodeficiency has not been
JEADV 2015, 29, 1978–1994
reported, but two patients had chronic lymphocytic leukaemia.10 Both our patients with organ transplant had already developed SCC years before SEDC, and two patients from the literature also had a past history of non melanoma skin cancers.34,36 Wasserman et al (table 6) and Clarck et al (table 6). SEDC could therefore be added to the list of tumours that can develop in organ transplant patients. SEDC seems to have a worse prognosis than MAC/SC as one of our patients had local recurrences and another died after complete excision could not been achieved. Although the first reports did not mention a particular evolution of SEDC, three recently reported patients developed regional lymph node and systemic metastases.27,29 Additional clinical data and longer follow-up are needed to clarify this point.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
By definition SEDC exhibits a double pattern, with squamous features predominating in superficial portions and syringomatous eccrine differentiation in the most invasive parts. The squamoid component usually resembles well to moderately well differentiated squamous cell carcinoma. The deep component is evokative of an eccrine origin, with possible perineural invasion. Our cases showed deeper invasion than previously reported, as 72% reached the subcutis (vs. 46%) and 43% the underlying structures (none of previously reported case). The histogenesis of SEDC is also controversial. Certain authors supported an eccrine origin with prominent squamous metaplasia in the ductal structures.9 Others pointed out the similarities with MAC and think SEDC is MAC with squamous features, because of prominent clear cells supposed to be reminiscent of sebaceous differentiation and areas of follicular keratinization.11 Our clinical and immunopathological findings allowed us to rule out this hypothesis. K77 was expressed in ductal structures of all our cases showing that luminal cells of the ductal component are of eccrine origin. We also noticed expression of K6, K16, K17 and K19 in inner structures, as in luminal cells of eccrine ducts and K7, K8 and K18 in the deepest strands, as in secretory cells of eccrine coils. Finally, squamoid differentiation has been reported in benign and malignant eccrine neoplasms.37 All together, our study confirmed the eccrine origin of SEDC.
Conclusion We report thirty cases of sclerosing sweat duct carcinomas composed of three distinct entities with different behaviours and histogenesis. Our study demonstrated that MAC and SC have similar clinical and epidemiological characteristics, although histogenesis differs, mainly follicular in MAC and eccrine in SC. We show arguments for the individualization of SEDC, because of its eccrine origin, more aggressive behaviour and possible occurrence in organ transplant.
Acknowledgements We would like to thank Prs Avril, Dupin, Saiag, Thomas, Drs Audibert, Berthelon-Vachette, Bocquet, Bonnemaison, Bosset, Bouqueau, Brahmi, Brudy, Capitant, Chaix, Christoffersen, Combe, Couder, Cury, Dailloux, Debarbieux, Delachapelle, Devico, Diner, Dumas, Duong, Enache, Espagne, Fahri, Fayard, Foyatier, Gaede, Genvo, Gorin, Gougne-Mahoudeau, GregoireBardel, Hardy, Henryon, Hureau, Janin, Kolb, Lecointre, Lefebvre-Oget, Letessier, Lipowicz, Mayer, Nollez, Olaiwan, Pawin, Pichot, Roth, Runge, Salles, Santoul, Sarfaty, Savary, Seltan, Thiriat, Valantin, Valette, Villaret, Wettervald, Wolff-Ram for clinical information and Mr Peltre for technical support.
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2 Goldstein DJ, Barr RJ, Santa Cruz DJ. Microcystic adnexal carcinoma: a distinct clinicopathologic entity. Cancer 1982; 50: 566–572. 3 Freeman RG, Winkelmann RK. Basal cell tumor with eccrine differentiation (eccrine epithelioma). Arch Dermatol 1969; 100: 234–242. 4 Cooper PH, Mills SE, Leonard DD et al. Sclerosing sweat duct (syringomatous) carcinoma. Am J Surg Pathol 1985; 9: 422–433. 5 Urso C, Bondi R, Paglierani M, Salvadori A, Anichini C, Giannini A. Carcinomas of sweat glands: report of 60 cases. Arch Pathol Lab Med 2001; 125: 498–505. 6 Ohtsuka H, Nagamatsu S. Microcystic adnexal carcinoma: review of 51 Japanese patients. Dermatology 2002; 204: 190–193. 7 Pujol RM, LeBoit PE, Su WP. Microcystic adnexal carcinoma with extensive sebaceous differentiation. Am J Dermatopathol 1997; 19: 358–362. 8 Smith KJ, Skelton HG, Holland TT. Recent advances and controversies concerning adnexal neoplasms. Dermatol Clin 1992; 10: 117–160. 9 Wong TY, Suster S, Mihm MC. Squamoid eccrine ductal carcinoma. Histopathology 1997; 30: 288–293. 10 Terushkin E, Leffell DJ, Futoryan T, Cowper S, Lazova R. Squamoid eccrine ductal carcinoma: a case report and review of the literature. Am J Dermatopathol 2010; 32: 287–292. 11 Kavand S, Cassarino DS. “Squamoid eccrine ductal carcinoma”: an unusual low-grade case with follicular differentiation. Are these tumors squamoid variants of microcystic adnexal carcinoma? Am J Dermatopathol 2009; 31: 849–852. 12 Langbein L, Cribier B, Schirmacher P, Praetzel-Wunder S, Peltre B, Schweizer J. New concepts on the histogenesis of eccrine neoplasia from keratin expression in the normal eccrine gland, syringoma and poroma. Br J Dermatol 2008; 159: 633–45. 13 Sellheyer K, Krahl D. PHLDA1 (TDAG51) is a follicular stem cell marker and differentiates between morphoeic basal cell carcinoma and desmoplastic trichoepithelioma. Br J Dermatol 2011; 164: 141–147. 14 Avraham JB, Villines D, Maker VK, August C, Maker AV. Survival after resection of cutaneous adnexal carcinomas with eccrine differentiation: risk factors and trends in outcomes. J Surg Oncol 2013; 108: 57–62. 15 Stam H, Lohuis PJ, Zupan-Kajcovski B, Wouters MW, van der Hage JA, Visser O. Increasing incidence and survival of a rare skin cancer in the Netherlands. A population-based study of 2,220 cases of skin adnexal carcinoma. J Surg Oncol 2013; 107: 822–827. 16 Hansen T, Kingsley M, Mallatt BD, Krishnan R. Extrafacial microcystic adnexal carcinoma: case report and review of the literature. Dermatol Surg 2009; 35: 1835–1839. 17 Alessi E, Caputo R. Syringomatous carcinoma of the scalp presenting as a slowly enlarging patch of alopecia. Am J Dermatopathol 1993; 15: 503– 505. 18 Chiller K, Passaro D, Scheuller M, Singer M, McCalmont T, Grekin RC. Microcystic adnexal carcinoma: forty-eight cases, their treatment, and their outcome. Arch Dermatol 2000; 136: 1355–1359. 19 Cooper PH, Mills SE. Microcystic adnexal carcinoma. J Am Acad Dermatol 1984; 10: 908–914. 20 Kato H, Mizuno N, Nakagawa K, Furukawa M, Hamada T. Microcystic adnexal carcinoma: a light microscopic, immunohistochemical and ultrastructural study. J Cutan Pathol 1990; 17: 87–95. 21 Slodkowska EA, Cribier B, Peltre B, Jones DM, Carlson JA. Calcifications associated with basal cell carcinoma: prevalence, characteristics, and correlations. Am J Dermatopathol 2010; 32: 557–564. 22 Yamamoto T, Irifune A, Katayama I, Nishioka K. Calcification of eccrine poroma. J Dermatol 1994; 21: 979–981. 23 Hoang MP, Dresser KA, Kapur P, High WA, Mahalingam M. Microcystic adnexal carcinoma: an immunohistochemical reappraisal. Modern Pathol 2008; 21: 178–185. 24 Sellheyer K, Nelson P, Kutzner H, Patel RM. The immunohistochemical differential diagnosis of microcystic adnexal carcinoma, desmoplastic trichoepithelioma and morpheaform basal cell carcinoma using BerEP4 and stem cell markers. J Cutan Pathol 2013; 40: 363–370.
© 2015 European Academy of Dermatology and Venereology
1994
25 Yamamoto O, Hamada T, Doi Y, Sasaguri Y, Hashimoto H. Immunohistochemical and ultrastructural observations of desmoplastic trichoepithelioma with a special reference to a morphological comparison with normal apocrine acrosyringeum. J Cutan Pathol 2002; 29: 15–26. 26 Langbein L, Rogers MA, Praetzel S et al. Characterization of a novel human type II epithelial keratin K1b, specifically expressed in eccrine sweat glands. J Invest Dermatol 2005; 125: 428–444. 27 Wang B, Jarell AD, Bingham JL, Bonavia GH. PET/CT imaging of squamoid eccrine ductal carcinoma. Clin Nucl Med 2015; 40: 322–324. 28 Jung YH, Jo HJ, Kang MS. Squamoid eccrine ductal carcinoma of the scalp. Korean J Pathol 2012; 46: 278–281. 29 Kim JW, Jeon MK, Kang SJ, Sun H. Surgical management of recurrent squamoid eccrine ductal carcinoma of the scalp. J Craniofac Surg 2012; 23: e276–e278. 30 Sidiropoulos M, Sade S, Al-Habeeb A, Ghazarian D. Syringoid eccrine carcinoma: a clinicopathological and immunohistochemical study of four cases. J Clin Pathol 2011; 64: 788–792.
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31 Herrero J, Monteagudo C, Jorda E, Llombart-Bosch A. Squamoid eccrine ductal carcinoma. Histopathology 1998; 32: 478–480. 32 Kim YJ, Kim AR, Yu DS. Mohs micrographic surgery for squamoid eccrine ductal carcinoma. Dermatol Surg 2005; 31: 1462–1464. 33 Chhibber V, Lyle S, Mahalingam M. Ductal eccrine carcinoma with squamous differentiation: apropos a case. J Cutan Pathol 2007; 34: 503–507. 34 Wasserman DI, Sack J, Gonzalez-Serva A, Konnikov N, Bohac G, Demierre MF. Sentinel lymph node biopsy for a squamoid eccrine carcinoma with lymphatic invasion. Dermatol Surg 2007; 33: 1126–1129. 35 Pusiol T, Morichetti D, Zorzi MG, Piscioli F. Squamoid eccrine ductal carcinoma: inappropriate diagnosis. Dermatol Surg 2011; 37: 1819–1820. 36 Clark S, Young A, Piatigorsky E, Ravitskiy L. Mohs micrographic surgery in the setting of squamoid eccrine ductal carcinoma: addressing a diagnostic and therapeutic challenge. J Clin Aesthet Dermatol 2013; 6: 33–36. 37 Kohda M, Manabe T, Ueki H. Squamous islands in eccrine neoplasms. Am J Dermatopathol. 1990; 12: 344–349.
© 2015 European Academy of Dermatology and Venereology
DOI: 10.1111/jdv.13127
ORIGINAL ARTICLE
Anatomoclinical study of 30 cases of sclerosing sweat duct carcinomas (microcystic adnexal carcinoma, syringomatous carcinoma and squamoid eccrine ductal carcinoma) E. Frouin,1,*,† M.D. Vignon-Pennamen,2,3,† B. Balme,4,† B. Cavelier-Balloy,2,5,† U. Zimmermann,3,6,† ,9 B. Cribier10,† N. Ortonne,7,† A. Carlotti,8,† L. Pinquier,2,4,† J. Andre ^pital Jean Bernard, CHU, Poitiers, France Laboratoire d’Anatomie et de Cytologie Pathologiques, Ho ^pital Saint Louis, APHP, Paris, France Service d’Anatomie pathologique, Ho 3 e de la Roquette, 56 rue de la Roquette, Paris, France Centre de Pathologie cutane 4 Laboratoire d’Anatomie pathologique, Centre hospitalier Lyon Sud, Lyon, France 5 Cabinet d’Anatomie pathologique dermatologique, 35 avenue Mathurin Moreau, Paris, France 6 ^pital Ambroise Par Laboratoire d’Anatomie pathologique, Ho e, APHP, Boulogne-Billancourt, France 7 ^pital Henri Mondor, APHP, Cre teil, France D epartement de Pathologie, Ho 8 ^pital Cochin-Tarnier, APHP, Paris, France Service d’Anatomie et de cytologie pathologiques, Ho 9 Centre d’Anatomie pathologique et de cytologie, Avenue du Diamant, Bruxelles, Belgium 10 e, Clinique Dermatologique, Ho ^pital Civil, Strasbourg, France Laboratoire d’Histopathologie cutane *Correspondence: E. Frouin. E-mail: [email protected] 1 2
Abstract Background Microcystic adnexal carcinoma (MAC), syringomatous carcinoma (SC) and “Squamoid eccrine ductal carcinoma” (SEDC) are rare sclerosing adnexal tumours. Objective To understand the histogenesis of these tumours and possible clinical implications. Methods We conducted a retrospective study of 30 cases, 18 MAC, 5 SC and 7 SEDC reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts, and PHLDA1 expressed in adnexal structures. Results There was a strong female predominance, with only five cases occurring in men. Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Two cases of SEDC were found in organ transplant patients. No recurrence or metastases were observed after complete surgery of MAC, or SC (mean follow-up 7.2 years and 4.7 years), whereas one case of SEDC recurred and another could not be fully excised. MAC and SC had similar histological features, except for cysts. In MAC, calcifications, granulomas, connection to follicles, keratin expression pattern, PHLDA1 positivity and K77 negativity indicated a follicular histogenesis, whereas in SC, K77 positivity and keratin expression pattern were consistent with a differentiation towards eccrine apparatus. SEDC was composed of strands centred by ducts and nests with squamous differentiation and displayed K77 ductal positivity in all cases, a finding consistent with an eccrine origin. Conclusion Our study demonstrated that MAC and SC have similar clinical characteristics, although histogenesis differs and show arguments for the individualization of SEDC. Received: 5 January 2015; Accepted: 2 March 2015
Conflict of interest and source of funding The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Introduction Skin adnexal carcinomas are rare neoplasms with an incidence rate of 5.1 per 1 million person-years.1 Microcystic adnexal †
French dermatopathological section of the French Dermatological Society
(SFD). Collaborators from the French dermatopathological section of the French Dermatological Society SFD: Plantier F; Clerici T; Moulonguet I; Moguelet P; Sass U; Le Pelletier F; Truchetet F; Baudin M; Petit T; Lemasson G; Grossin M;.
JEADV 2015, 29, 1978–1994
carcinoma (MAC) and syringomatous carcinoma (SC) are one of the most frequents. Since the first reports,2,3 many names were given to these entities reflecting controversies regarding histogenesis. In 1985, Cooper et al.4 proposed the term “Sclerosing sweat duct carcinoma” (SSDC), and pointed out the similarities between the two entities. These tumours consist of slowly growing and indurated plaques that cannot be differentiated
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1979
from one another. Location seems to differ as SC predominates on the scalp, whereas MAC is located on the middle of the face.5,6 As metastases are very uncommon, Smith et al. and further Pujol et al. proposed the term of “locally aggressive adnexal carcinomas” (LAAC) with variations in histopathological findings.7,8 Recently, Wong et al.9 reported four tumours showing strands centred by ducts and nests with squamous differentiation which they called “squamoid eccrine ductal carcinoma” (SEDC). Since then, other authors emphasized that this tumour may be misdiagnosed as squamous cell carcinomas (SCC). Evolution of SEDC seems to be distinct from those of SCC, as local recurrence rate is high, although metastases are rare.10 Accordingly, a link between MAC and SEDC has been recently evoked.11 To understand the histogenesis of MAC, SC and SEDC and possible clinical implications, we conducted a clinicopathological study of 30 cases, reviewed and classified by a panel of dermatopathology experts, with immunohistochemical analysis of keratins, including K77, a new keratin specific of eccrine ducts,12 and PHLDA1 (TAG-2) expressed in follicular and eccrine structures.13
Material and methods Twenty members of the Dermatopathology group of the French Society of Dermatology retrieved from their own
collection all cases of eccrine carcinomas diagnosed between 1995 and 2008. All cases were reviewed and classified by the panel. All cases retained followed previously reported histological criteria.2,4,9 Briefly, all tumours were made of deeply invasive basaloid strands with ductal differentiation suggestive of eccrine origin. Tumours with keratinizing cysts were classified as MAC. Those composed of strands without cysts or parakeratotic island, were classified as SC. Tumours showing squamous differentiation, i.e. islands with parakeratotic keratinization were classified as SEDC. Clinical information and follow-up were obtained from dermatologists and general practitioners. We looked for past medical history, especially malignancy (location, duration, radiation and chemotherapy). We studied the type of treatment (size of margins, number of procedures needed, Mohs surgery), number of recurrences before and after treatment of the lesion studied, and follow-up. Histological analyses were performed on routinely formalin fixed tissues except for a few cases fixed with Bouin solution; 36 samples (24 excisions and 12 biopsies), were examined. We obtained more than one sample of the tumour in five patients.
Table 1 Immunohistochemistry material and methods Antibody name
Clone (origin)
Type of antibody
Dilution
Antigen retrieval
Time of incubation
AE1/AE3
AE1AE3 (Dako)
Monoclonal (mouse)
1/50
Citrate
20 min
KL1
KL1 (Immunotech)
Monoclonal (mouse)
None
Citrate
20 min
K1
anti-human K1.1-gp (Langbein)
Polyclonal (guinea pig)
1/1000
EDTA
24 h
K5
Anti-human CK5.2-gp (Langbein)
Polyclonal (guinea pig)
1/1000
EDTA & Trypsine
24 h
K6
Anti-human KA12 (Langbein)
Monoclonal (mouse)
1/100
EDTA
24 h
K7
OV-TL 12/30 (Dako)
Monoclonal (mouse)
1/25
Citrate
20 min
K8
35bH11 (Dako)
Monoclonal (mouse)
1/50
Citrate & Trypsine
20 min
K10
Anti-human DE-K10 (Langbein)
Monoclonal (mouse)
1/1000
EDTA
24 h
K14
CK14.2 (Langbein)
Polyclonal (guinea pig)
1/1000
Citrate & Trypsine
24 h
K16
CK16.1 (Langbein)
Monoclonal (mouse)
1/200
EDTA
24 h
K17
E3 (Dako)
Monoclonal (mouse)
1/100
Citrate & Proteinase K
20 min
K18
DC10 (Dako)
Monoclonal (mouse)
1/10
Citrate & Proteinase K
20 min
K19
RCK108 (Dako)
Monoclonal (mouse)
1/50
Citrate & Trypsine
20 min
K77
Anti-human CKT5N.2-gp (Langbein)
Polyclonal, (guinea pig)
1/500
EDTA
24 h
PHLDA1
RN-6E2 (Santa-Cruz)
Monoclonal, (mouse)
1/25
EDTA
20 min
ACE
12.140.10 (Novocastra)
Monoclonal (mouse)
None
Citrate
20 min
EMA
E29 (Dako)
Monoclonal (mouse)
1/100
Citrate
20 min
PS100
NCL-L-S100p (Novocastra)
Polyclonal (rabbit)
1/5
Citrate
20 min
Actin
1A4 (Dako)
Monoclonal (mouse)
1/200
EDTA
45 min
GCDFP15
D6 (Covance)
Monoclonal (mouse)
1/100
EDTA
20 min
Ber-EP4
Ber-EP4 (Dako)
Monoclonal (mouse)
1/100
Citrate
20 min
P63
4A4 (Santa Cruz)
Monoclonal (mouse)
1/25
EDTA
20 min
Ki-67
MIB-1 (Dako)
Monoclonal (mouse)
1/20
EDTA
20 min
The table resume the characteristics of each antibody (Ab) used in this study. Sections were heated for antigen retrieval in sodium citrate buffer pH 6.0 (Citrate) or in EDTA pH7.8 (EDTA) followed by trypsinization for 3 min at 37°C (Trypsine) or proteinase K digestion for 5 min (Proteinase K). Some antibodies, especially keratins, were kindly supplied by Lutz Langbein, Heidelberg, Germany (Langbein).
JEADV 2015, 29, 1978–1994
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
MAC
8
MAC
MAC
7
12
MAC
6
MAC
MAC
5
11
MAC
4
MAC
MAC
3
10
MAC
2
MAC
MAC
1
9
Diagnosis
Case
F
F
F
F
F
F
F
F
F
F
F
F
Sex
52
45
56
88
41
46
73
24
75
65
68
73
Age (years)
CLL (untreated for 12 years)
Cervix cancer treated by surgery and curietherapy 4 years before
Past medical history
Scalp
Eyebrow (left)
Nose (left)
Cheek (right)
Back
Eyebrow (left)
Cheek
Lip
Nose (left)
Cheek (right)
Scalp
Nose
Location of tumour
6
1
1 (recurrent tumour)
4 (recurrent tumour)
1,3
Unknown
0,2
3
3
1
1,5 (recurrent tumour)
10
Duration of tumour prior first treatment (years)
Table 2 Clinical characteristics of the 30 cases of sclerosing sweet ducts carcinomas
3
1.2
0.3
Unknown
0.5
1
0.5
0.4
Large (check, nose)
2
3.5
2
Tumour size (cm)
Painful indurated erythematous plaque with scales
Nodule
Sclerodermoid plaque with telangiectasia
Indurated plaque
Bluish indurated nodule
Nodule
Plaque
Indurated and ulcerated nodule
Nodules under indurated plaque
Ulcerated and crusted nodule
Ulcerated nodule
Erythematous indurated plaque
Clinical description
Conventional surgery (2 procedures; large margins) Conventional surgery followed by slow Mohs surgery (5 procedures)
dTE
Unknown
Conventional surgery (1 procedure; large margins)
BCC
11.2 (A)
5.9 (A)
5.5 (A)
4.5 (DND)
6.6 (A)
Conventional surgery (2 procedures; 2 cm margin)
Conventional surgery (2 procedures; 1 cm margin)
6.5 (A)
5.4 (A)
5.7 (A)
11.2 (A)
12.9 (A)
4 (A)
2.9 (A)
Follow-up (year and status)
Conventional surgery (3 procedures; margin unknown)
Conventional surgery (2 procedures; 0.5 cm margin)
Conventional surgery (4 procedures; 2 cm margin)
Conventional surgery (2 procedures; large margins)
Conventional surgery (1 procedure; 3 cm margin)
Mohs surgery (3 procedures; large margins)
Conventional surgery (2 procedures; 1 cm margin)
Surgical treatment
BCC
BCC, melanoma, granuloma annulare, morphea
Unknown
BCC
Unknown
Sarco€ıdosis
Unknown
BCC, dTE
Unknown
Clinical diagnosis evoked
1980
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
SC
SC
19
23
MAC
18
SC
MAC
17
22
MAC
16
SC
MAC
15
21
MAC
14
SC
MAC
13
20
Diagnosis
Case
Table 2 Continued
F
F
F
M
F
M
M
M
F
F
F
Sex
52
67
36
27
53
63
43
55
59
52
30
Age (years)
4 month pregnant
Past medical history
Cheek (left)
Lower eyelid (left)
Cheek (left)
Cheek (left)
Nasolabial (left)
Forehead
Eyebrow (right)
Eyebrow (right)
Arm (left)
Scalp
Thigh (left)
Location of tumour
Unknown
0.2
Recent lesion
Unknown
Large
4
0.5
3.9
3.5
0.3
3.5
1.5
0.4
Tumour size (cm)
Unknown
1
25 (recurrent tumour)
1
0,4
10
2
15
Unknown
Duration of tumour prior first treatment (years)
Indurated plaque
Nodule
Indurated plaque
Indurated plaque
Nodule on indurated plaque
Indurated and ulcerated plaque
Indurated plaque
Indurated plaque
Painful indurated plaque
Plaque
Indurated plaque
Clinical description
BCC
BCC
Unknown
DFPS
Slow Mohs surgery
Conventional surgery (1 procedure; 0.5 cm margin)
Conventional surgery (1 procedure; 1.5 cm margin)
Conventional surgery (1 procedure; 1 cm margin) and lymph node excision (negative)
Conventional surgery (3 procedures; 1 cm margin)
Unknown
3.3 (A)
5.5 (A)
4 (A)
4.8 (A)
5.9 (A)
9.5 (A) Conventional surgery (2 procedures; 1 cm margin)
BCC
Lymphoma, cutaneous mucinosis
8.5 (A)
2 (A)
10.6 (A)
12.4 (A)
Follow-up (year and status)
4.4 (A)
Conventional surgery followed by slow Mohs surgery (1 procedure) and Lymph node excision (negative)
Conventional surgery (1 procedure; 3 cm margin) and Lymph node excision (negative)
Conventional surgery (1 procedure; 0.3 cm margin)
Conventional surgery (3 procedures; 2 cm margin)
Surgical treatment
Conventional surgery (2 procedures; 1 cm margin)
sBCC
DFSP
BCC
Dermatofibroma
Clinical diagnosis evoked
Sclerosing sweat duct carcinomas 1981
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
SEDC
SEDC
27
28
F
F
M
F
F
F
F
Sex
96
76
80
71
91
81
74
Age (years)
SSM Breast cancer (radiation, surgery)
Bowen disease, BCC, SCC Liver transplantation 11 years before (cyclosporin)
Bowen disease, BCC, SSM
Kidney transplantation 15 years before (cyclosporin and corticosteroid) SCC 11 years before
Past medical history
Cheek (right)
Cheek (right)
0.4
1
0.5
4.0
Unknown
7.8
0.5
Unknown
Internal canthus (right)
Cheek (right)
Unknown
0.3
Unknown
1.5
Tumour size (cm)
Nose (left)
Unknown
2 (recurrent tumour)
Nose
Forehead
Duration of tumour prior first treatment (years)
Location of tumour
Unknown
Nodule
Induration with scales
Erythematous plaque with scales
Indurated and ulcerated nodule
Unknown
Nodule
Clinical description
SCC
BCC
Conventional surgery (4 cm margin) followed by slow Mohs surgery (5 procedures) with incomplete margins
Large conventional surgery
Conventional surgery (2 procedures; margin unknown)
2.7 (recurrence; AWD)
4.5 (A)
3.7 (A)
7.7 (A) Conventional surgery (1 procedure; 1 cm margin) Switch from cyclosporin to tacrolimus Bowen disease, SCC, BCC
SCC
5.7 (A) Conventional surgery (1 procedure; margin unknown)
Unknown
13 (A)
3.5 (DOD)
Follow-up (year and status)
Conventional surgery (2 procedures; 2 cm margin)
Large conventional surgery (5 procedures) with enucleation, and nose amputation followed by radiation (65 Gy) Decreased cyclosporin and switch corticosteroid to sirolimus
Surgical treatment
Unknown
SCC
Clinical diagnosis evoked
A, alive without disease; AWD, alive with disease; BCC, basal cell carcinoma; CLL, chronic lymphocytic leukaemia; DFPS, dermatofibrosarcoma protuberans; DND, dead not of disease; DOD, dead of disease; dTE, desmoplastic trichoepithelioma; F, Female; M, male; MAC, microcystic adnexal carcinoma; SC, syringomatous carcinoma; SCC, squamous cell carcinoma; SEDC, Squamoid eccrine ductal carcinoma; sBCC, sclerodermiform basal cell carcinoma; SSM, superficial spreading melanoma.
SEDC
SEDC
26
30
SEDC
25
SEDC
SEDC
24
29
Diagnosis
Case
Table 2 Continued
1982
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1983
Imunohistochemistry
Antibody dilution and antigen retrieval techniques are summarized in Table 1. The labelled streptavidin biotin (LSAB) immunostaining kit (Dako) with biotinylated anti-guinea pig, anti-mouse or anti-rabbit IgG was used for visualization of bound antibodies. Haematoxylin was used for counterstaining.
Results One hundred and four tumours were reviewed and only 30 cases were retained for the present study, 18 were classified as MAC, five as SC and seven as SEDC. Other cases were eliminated because of diagnostic errors (other types of adnexal tumours, especially of follicular histogenesis), absence of ductal structures, features suggestive of other types of eccrine carcinomas. Clinical and epidemiological data
There was a strong female predominance, with only five cases occurring in men and very similar sex-ratio in the three groups (Tables 2 and 3). Patients with MAC and SC were younger (mean age 56 and 47 years) than those with SEDC (mean age 81 years). There were two young patients, one with MAC (24 years) and one with SC (27 years), whereas the older patient was 88 years and had MAC. The vast majority of tumours were located on the face (80%). The most common localization was the cheek in SC and SEDC and the periocular area in MAC. Duration before excision was long in MAC and SC, reaching 15 years in a patient with MAC and 25 years in another with SC. Three cases of MAC and two of SC were recurrent tumours.
A past medical history of skin cancers was found in four patients with SEDC. Two patients had had liver or renal transplant 10 and 15 years before the diagnosis of SEDC, whereas a patient was 4 months pregnant when MAC was diagnosed. None of our patients had radiotherapy at the site of sclerosing carcinoma or systemic chemotherapy before the diagnosis. The clinical description MAC was a plaque in 10 cases, indurated in nine cases, or a nodule in eight cases (44%) indurated in three. Pain was present only in two cases. The clinical aspect of SCs was a painless indurated plaque in four cases (80%) (Fig. 1), whereas SEDC consisted of painless nodule in two cases, erythematous plaque in 1 and “induration” in 1. The diagnosis of a sclerosing sweat duct carcinoma was never evoked by clinicians. Patients with MAC were all treated by surgery with healthy margins (mean 1.5 cm) in 12 cases; “large” margins were done in six cases. One to five surgical procedures were necessary to obtain free margins. In two patients, slow Mohs surgery followed conventional surgery. Patients with SC were all treated by surgery with healthy margins (mean 1 cm), one of them by slow Mohs surgery. One to three surgical procedures were necessary. All patients with SEDC had surgery, one of them with slow Mohs. One to five surgical procedures were needed (mean margins 2.3 cm). In one case, large excision with enucleation and nose amputation was required, followed by radiation therapy. Two patients with MAC had negative sentinel lymph node excision, and one patient with SC had a negative complete lymph node excision. No recurrence or metastases were observed during follow-up (mean 7.2 years in MAC and mean 4.7 years in SC). In patients
Table 3 Synthesis of epidemiological and clinical characteristics of the 30 cases of sclerosing sweet ducts carcinomas MAC
SC
SEDC
Number of cases
18
5
7
Sex (M : F)
3 : 15
1:4
1:6
Mean age (range)
56 (24–88)
47 (27–67)
81 (71–96)
Location of the lesions Face, n (%)
12 (67)
5 (100)
7 (100)
Lips, n (%)
1 (6)
1 (20)
0 (0)
Nose, n (%)
3 (17)
0 (0)
2 (29)
Cheek, n (%)
3 (17)
3 (60)
3 (43)
Forehead, n (%)
1 (6)
0 (0)
1 (14)
Ocular area, n (%)
4 (22)
1 (20)
1 (14)
Scalp, n (%)
3 (17)
0 (0)
0 (0)
Trunk, n (%)
1 (6)
0 (0)
0 (0)
Limbs, n (%)
2 (11)
0 (0)
0 (0)
Mean time duration (range)
3.7 years (0.2–15)
13 years (1–25)
0.8 years (0–2)
Size of the lesion (range)
1.7 cm (0.3–3.9)
1.5 (0.2–4)
3.4 cm (0.5–7.8)
Mean number of surgical procedures (range)
2.2 (1–5)
1.5 (1–3)
2.3 (1–5)
Mean size margin (range)
1.6 cm (0.3–3)
1 cm (0.5–1.5)
2.3 cm (1–4)
Mean follow-up (range)
7.2 years (2–12.9)
4.7 years (3.3–5.9)
5.8 years (2.7–13)
Recurrence or metastasis
None
None
2 recurrences
JEADV 2015, 29, 1978–1994
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
+
Basal cells
+
+
+
+
Poroid cells
Luminal cells of acrosyringium
+/
+/
+ (i)
+
+
+
Bulge
Follicular germinative cells
Outer sheath
+/
+
+
+/
+
+/
+/
+
+
+
K8
+/
+/
+ (i)
+ (i)
+/
+
+††
+
K10
+
+
+
+
+
+
+ (o)
+ (o)
+
+
+
+
+
+/ †
K14
+
+ (i)
+ (i)
+
+
+*
K16
+
+ (i)
+ (i)
+/
+
+*
K17
+/
+/
+
+
+
+
+
+
K18
+/
+
+
+
K19
+
+
K77
+ +
+
+
PHLDA1
+
+
BerEP4
*K6, K16, K17 and EMA were only positive in the suprabasal cells of reactive epidermis. †K14 was slightly positive in suprabasal epidermis in some lesions. ‡PS100 was positive in melanocytes and in Langerhans cells. §P63 was positive in basal and suprabasal cells but neither in inner nor in superficial cells of follicles and epidermis. ¶EMA highlighted the luminal cell pole of sweat ductular and secretory cells. **ACE highlighted the luminal cell pole of some sweat secretory cells. ††K10 was positive in luminal cells in the superficial part of the eccrine ducts. ‡‡GCDFP15 was slightly positive in the cytoplasm of luminal sweat duct cells. §§K7 was positive predominantly in outer sebocytes. +, positive; , negative; +/ , occasionally positive cells or inconstant positivity within lesions; i, only inner cells positive; o, only outer cells positive.
+/ §§
+
+
Sebaceous ducts
+
+ (i)
+ (i)
+/
Sebocytes
+
+
+
+
+ (o)
+
K7
+
+ (i)
+
+
*
K6
Undifferentiated cells
Sebaceous gland
Matrical cells
+
+ (i)
+
Isthmus
Inner sheath
+ (i)
+
Infundibulum
+ (o)
+
+
Luminal cells of ducts
+ (i)
+
+
Cuticular cells of ducts
Hair follicles
+
+
+
K5
+
+
+
K1
Myoepithelial cells
+
+
Kl1
Secretory cells
Eccrine sweat glands
+
Suprabasal cells
Epidermis
AE1/ AE3
Table 4 Immunohistochemical findings for all tested antibodies in normal skin, exception of Ki-67
+
+
+¶
+¶
+¶
+*
EMA
+
+
+**
ACE
+‡
+‡
+‡
+‡
_
_
_
+
+‡
+‡
S100
+
Actin
+‡‡
+‡‡
+
GCDFP15
+
+
+
+
+
+
+§
+§
+/
+
+
+
+§
P63
1984
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1985
with SEDC, one developed recurrence after 32 months and another had incomplete excision but none had metastases. This last patient died 42 months after diagnosis because of slowly growing, eroded, and bleeding tumour. In the others, no recurrence or metastasis were observed during follow-up (mean 5.8 years). Histopathological findings MAC (n = 18) All cases contained small cysts with a granular layer, centred by “glassy” or laminated keratin (Figs 2 and 3).
Strands predominated over cysts (12 cases) and were centred by ducts (16 cases). Tadpole structures were seen in eight cases (Fig. 3). Apocrine differentiation was present in two tumours (Fig. 3). Clear cells sometimes resembling sebaceous cells were seen in 11 cases (Fig. 3). Mitotic activity was low (1 per 10 high-power fields), without atypical mitoses nor cellular atypia. Tumour nests were connected to the follicles in seven cases. Foreign body type granuloma was present in 11 cases and calcification in three (Fig. 3). All tumours were deeply invasive (fat tissue n = 6, muscle n = 7, structures underlying muscles n = 3), with perineural invasion in seven cases (Fig. 3). SC (n = 5) All cases were made only of strands limited by smooth border, without cysts or nests (Fig. 4). Tadpole structures and ducts were always present (Fig. 4), without apocrine differentiation. Clear cells were present in two cases. There was no connection to the epidermis or follicles, but extension to fat tissue (n = 4), perineural invasion (n = 2). Mitoses were rare (< 1 per 10 HPF). No inflammation was noticed.
Figure 1 Sclerotic plaque of the left cheek of a 28 year-old man (Syringomatous carcinoma).
(a)
Figure 2 Silhouette of microcystic adnexal carcinomas. (a) MAC made predominantly of cysts with a few strands invading of the deep of the lip (HES, 9 1). (b) Deep strands surrounded by sclerotic stroma, with epidermal cysts in the upper part (HE, 9 4). (c) Deep dilated ducts with smooth borders centred by an eosinophilic material (HE, 9 4). (d) MAC of the scalp, composed of epidermal cysts connected to the epidermis associated with strands centred by ducts. (HE, 9 1).
JEADV 2015, 29, 1978–1994
SEDC (n = 7) Tumours were made of nests and strands with angulous borders (Fig. 5), and cysts lined by a granulous layer and centred by paraketatotic, laminated or glassy keratin (Fig. 5). Clear cells were noted in 2. Ducts were always present in the superficial nests and also in the deep strands (four cases), without signs of apocrine differentiation. All but one tumours were connected to the epidermis (Fig. 5). Strands invaded the deep dermis (n = 2 cases), fat tissue (n = 2), underlying muscle (n = 2) and cartilage (n = 1), with
(b)
(c)
(d)
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1986
(a)
(d)
(b)
(c)
(e)
(h)
(f)
(g)
(i)
Figure 3 Histological features of MAC. (a) Cysts centred by glassy keratin (HE, 9 10). (b) Cysts centred by keratin reminiscent of epidermal cysts (HE, 9 10). (c) Clear cells within islands centred by cysts (HE, 20). (d) Tumour nests and cysts occasionally calcified (HE, 9 20). (e) Inflammatory granulomatous reaction (HES, 9 10). (f) Clear cells resembling sebaceous cells – (HES, 9 20). (g) Perineural invasion in deep adipose tissue (HES, 9 20). (h) Ducts with features suggestive of apocrine differentiation (HE, 9 20). (i) Collagenic stroma in deep strands (HE, 9 10).
perineural (n = 4) and perivascular invasion (n = 4) (Fig. 5). Nuclear atypia was seen in one tumour (Fig. 5), and mitoses in two (2–5 per HPF) (Fig. 5). Immunohistochemical findings
Tables 4 and 5 show an overview of immunohistochemical results. MAC A sequential pattern keratine expression was observed.
All cases strongly expressed K14. K5, K1, K10, K6 and K16 were strongly expressed in almost all cases, preferentially in the upper parts, and lightly in strands (Fig. 6). K17 labelled cysts, nests and strands, but never ducts, whereas luminal cells of ducts expressed K7. K8, K18 and K19 were expressed strongly and diffusely in
JEADV 2015, 29, 1978–1994
deep strands, in luminal cells of ducts, but also in outer cell rows of cysts (Fig. 6). K77 was expressed in only two cases, mainly in ducts (Fig. 6). GCDFP15 and Ber-EP4 were constantly negative. PHLDA1 staining displayed two different patterns, moderate positivity in upper nests and diffuse expression in strands and ducts (Fig. 6). Mean proliferation index (Ki-67) was 3.8% (range 1–15%). SC K5 and K14 were diffusely expressed. K1 and K10 were positive in only one case. K6 and K16 labelled ducts, whereas strands were positive only for K6. K17 was expressed only in strands. Certain ducts expressed K7, whereas ducts and strands were constantly positive with K8, K18 and K19. K77 was expressed in ducts (Fig. 6).
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
1987
(a)
(c)
(b)
(d)
(e)
Figure 4 Histopthological findings in syringomatous carcinoma (SC). (a) Deeply invasive strands within collagenic and mucinous stroma (HE, 9 2). (b–c), SC composed of round well-formed ducts and few strands (HE, 9 4 and HE, 9 10 respectively). (d–e), Case A at higher magnification showing tadpole appearance of ducts lined by one to two cell rows and neural invasion (HE, 9 20).
Ber-EP4 and GCDFP-15 were always negative. PHLDA1 was strongly positive in 2/3 cases in strands and ducts (Fig. 6). Mean Ki-67 was lower than 1%. SEDC K14 was diffusely positive, whereas K5 was slightly posi-
tive in basal layers of nests/cysts, strongly in strands. K1 and K10 predominated in superficial nests and cysts (Fig. 7). Keratin 6 and 16 were expressed in inner portions of epidermoid nests, whereas only K6 strongly labelled deep strands (Fig. 7). K17 had a similar diffuse expression as K6, but also strongly labelled ducts (Fig. 7). K8, K18 and K19 were positive in strands and ducts (Fig. 7), whereas K7 was positive in ducts of two cases. Keratin 77 was always positive in ducts (Fig. 7). Ber-EP4 and GCDFP-15 were constantly negative. PHLDA1 was positive mainly in the deepest parts of strands, slightly positive in nests (Fig. 7). Mean Ki67 was 4% (range 1–15%).
Discussion As many cases of MAC were reported under the name of SC and conversely, with incomplete description, the review of literature is very difficult. Even recent studies were published without detailed pathological review.1,14,15 Our study of SSDC selected by a panel of dermatopathologists was performed to determine
JEADV 2015, 29, 1978–1994
if subgroups can be identified on the basis of pathology/immunohistochemistry and if they are relevant for clinical management. Our study pointed out many clinical similarities between MAC and SC, as both occur mainly on the cephalic extremity of adults in their 50s. It has been widely reported that SC predominates on the scalp and presents as a slowly enlarging alopecic plaque, whereas MAC presents as a slowly growing plaque or nodule of the nasolabial fold or periocular area. We found similar anatomical distribution and clinical presentation in both groups, including uncommon extra-cephalic cases. Pain due to perineural involvement is regarded as a possible symptoms but was rarely observed in our experience. Lack of pain can account for the long duration before treatment. Hansen et al.16 noticed 14% of MAC present for more than 5 years and some up to 25 years. Both MAC and SC can measure up to 10 cm,6,17 which explains difficult surgical management. Surgery is the best treatment, ideally Mohs surgery which allows a lower rate of recurrence.18 After a mean follow-up of 4.7 and 7.2 years, respectively, none of our patients developed recurrences after complete surgery. Sentinel and prophylactic large lymph node excisions were performed in three of our patients and all were
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1988
(a)
(c)
(f)
(b)
(d)
(g)
(e)
(h)
Figure 5 Histological silhouettes and features of SEDC. Epidermoid nests centred by ducts and strands invading the muscle. Tumour covered by hyperplasic and hyperkeratotic epidermis (a HES, 9 1; b HES, 9 1). (a–b), Connection to epidermis, and ductal pattern (a, HES, 9 10) or epidermoid pattern (b, HE, 9 10). (c) Epidermoid nest centred by a duct (HES, 9 20). (d–e), Ducts showing typical cribriform pattern (d HES, 9 20; e HES, 9 10). Note nuclear atypia in a cell lining cribriform duct (d). (f) Parakeratotic keratinization in deepest parts (f HE, 9 10). (h) Perivascular invasion (HE, 9 4). (i) Mitosis within epidermoid islands (HE, 9 20).
negative. Lymph node or visceral metastases of MAC or SC are rare and prophylactic lymph node excision should not be performed. Finally, our study confirms that the prognosis of MAC and SC is good, as metastases are rare, but local invasion might be severe and needs extensive surgery to avoid recurrences. We observed a majority of common histopathological features in MAC and SC, except for cysts which are absent by definition
JEADV 2015, 29, 1978–1994
in SC. Cysts might be overlooked if step sections are not performed or in small biopsies. Another classic difference is the abundance of ducts in SC, whereas they can be sparse in MAC, but we observed ducts in all our cases of MAC. The histogenesis of MAC remains controversial, whereas SC is generally believed to belong to eccrine tumours. First, MAC was considered as an eccrine tumour, because of similarities with SC in its deepest portions. Epidermal cysts, foci of sebaceous differ-
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
10/11 (o)
10/11 (o)
0/12
0/11
12/12 (o)
0/11
K18
K19
K77
Ber-EP4
PHLDA1
ACE
5/5 (o)
0/5
2/11
8/11
0/11
0/11
0/12
0/11
2/12
8/11 (o)
10/11 (o)
11/11
8/11 (i)
11/11
6/11 (i)
10/11 (o)
0/11
9/11 (i)
6/11 (o)
2/11 (i)
11/11 (i)
5/5
0/5
0/11
8/11
7/11
0/11
12/12
0/11
0/12
10/11
11/11
11/11
1/11
11/11
2/11 (i)
11/11
0/11
5/11 (i)
9/11
0/11
11/11 (i)
11/11
Strands
5/5 (o)
0/5
0/11
0/11
7/11
9/11
12/12
0/11
2/12
10/11
11/11
0/11
3/11 (i)
11/11
2/11 (i)
11/11
7/11
3/11 (i)
5/11
0/11
11/11 (i)
11/11
Ducts
1/1
0/1
0/3
1/3
2/3
0/3
2/3†
0/3
0/5
0/3
0/3
0/3
0/3
3/3
0/3
0/3
0/3
0/3
1/3 (o)
0/3
0/1
3/3
1/1
0/1
1/3
1/3
2/3
0/3
2/3†
0/3
1/5 (i)
2/3
3/3
2/3
0/3
3/3
1/3
3/3
0/3
1/3
2/3
1/3
1/1
3/3
Strands
0/1
0/1
0/3
0/3
2/3
2/3
2/3†
0/3
4/5
2/3
3/3
0/3
1/3
3/3
1/3
3/3
1/3
3/3
2/3
1/3
0/1
3/3
Ducts
2/2
0/2
0/6
6/6
4/6
0/6
4/7 (o)
0/6
0/7
0/6
2/6
3/6
6/6 (i)
6/6
6/6 (i)
1/6
0/6
6/6 (i)
6/6
6/6 (i)
6/6 (i)
6/6
Islands and nests
SEDC (n = 6*) Cysts
2/2
0/2
0/6
6/6
4/6
0/6
0/7
0/6
0/7
0/6
0/6
3/6
6/6 (i)
6/6
6/6 (i)
0/6
0/6
6/6 (i)
0/6
6/6 (i)
6/6 (i)
6/6
Strands
2/2
0/2
1/6
0/6
6/6
0/6
4/7
0/6
1/7 (i)
2/6
4/6
3/6
2/6
6/6
6/6
2/6
2/6 (i)
6/6
6/6
0/6
1/6
6/6
Ducts
0/2
0/2
0/6
0/6
6/6
4/6‡
0/7
0/6
7/7
2/6
3/6
6/6
1/6
6/6
6/6
2/6
2/6
4/6
0/6
0/6
1/6
6/6
*For one case of MAC, SC and SEDC each only K77 and PHLDA1 were tested, whereas for five cases of MAC, one case of SC, and two cases of SEDC GCDFP15 and P63 were tested in supplement. †PHLDA1 has been evaluated only in three SC. ‡ACE was positive only in ducts within epidermoid islands and aggregates, but not in ducts within strands. It labelled strongly material within ducts and only slightly luminal cells. i, inner cells of the islands, nodules, nests, strands, cysts; o, outer cells of islands, nodules, nests, strands, cysts.
5/5
11/11
K17
P63
3/11 (i)
K16
0/5
11/11
K14
GCDFP-15
4/11 (i)
K10
0/11
10/11 (o)
K8
Actine
0/11
K7
8/11
9/11 (i)
K6
S100
7/11 (o)
K5
3/11
1/11 (i)
K1
EMA
11/11 (i)
KL1
11/11
Cysts
Islands and nests
11/11
Islands and nests
AE1/AE3
SC (n = 3*)
MAC (n = 11*)
Table 5 Immunohistochemical findings in 12 cases of Microcystic adnexal carcinoma (MAC), five cases of Syringomatous carcinoma (SC) and seven cases of Squamoid eccrine ductal carcinoma (SEDC)
Sclerosing sweat duct carcinomas 1989
© 2015 European Academy of Dermatology and Venereology
JEADV 2015, 29, 1978–1994
85
86
54
53
53
75
Wong et al.9
Wong et al.9
Herrero (1998)31
Kim (2005)
Chhibber (2007)33
Wasserman (2007)34
Kavand and Cassarino11
Terushkin et al.10
Sidiropoulos et al.30*
Pusiol (2011)35
Jung et al.28
Kim et al.29
Clark (2013)36
Wang et al.27
2
3
4
5
6
7
8
9
10
11
12
13
14
15
W
M
M
M
Progressive swelling, erythema and tenderness surrounding an exophytic tumour
Indurated plaque
Slowly growing reddish solitary nodule
Itchy, ulcerated and growing nodule
Slowly growing nodule
Mass
Solitary dermal nodule
Slowly growing nodulo-cystic lesion
Perly telangiectatic plaque with rolled border and central crust
Scabby nodule
Asymptomatic, slow growing reddish coloured eroded nodule
NA
Solitary dermal nodule
Solitary dermal nodule
Solitary dermal nodule
Clinical presentation
16 NA
Left index
26
26
12
NA
27
NA
9
NA
25
20
25
25
25
Size (mm)
Left clavicle
Scalp
Right occiput
Right tibia
Chest
Left Cheek
Great toe
Supra-sternal area
Left forearm
Right side of neck
Right knee
Axilla
Dorsum of hand
Left ear
Location
NA
NA
NA
NA
> 10 years
5.5 months
NA
NA
NA
NA
Ganglion cyst
NA
NA
Keloid or SCC
NA
NA
NA
NA
Clinical diagnosis
10 years
1 year
NA
1 year
3.5 years
1 yr
Several months
4 years
10 years
2 years
2 years
2 years
Duration before diagnosis
N
N
N
N
N
N
N
N
N
Y (3 times because of shave biopsies)
N
NA
N
N
N
Recurrence before diagnosis of SEDC
SCC
N
NA
N
N
SEC
NA
SEDC
N
SCC (on shave excision)
SCC
NA
NA
NA
SEDC
First histopathological diagnosis (if different)
*The third case reported by Sidiropoulos et al. as syringoid eccrine carcinoma displayed keratinization and follow criteria of SEDC. Y, Yes, N, No, NA, not available, SCC, squamous cell carcinoma, SEC, syringoid eccrine carcinoma.
91
W
60-64
W
M
W
61
63
M
M
W
M
W
M
M
Sex
68
90
30
41
81
Wong et al.9
1
32
Age (years)
Reference
Case
Table 6 Clinical and therapeutic findings of cases of SEDC previously reported
Y (multiple systemic metastases)
N
Y (lymph node)
Y (lymph node)
NA
N
N
N
N (after sentinel lymph node biopsy)
NA
N
N
N
N
N
Lymph node or systemic metastasis
12 2
Amputation
24
5
NA
NA
10
8
12
5
14
NA
5
3
NA
Follow-up (month)
MMS
Conventional excision
Conventional excision
Conventional excision
Conventional excision
MMS
Amputation
Conventional excision
Excisional biopsy
MMS
NA
Conventional excision
Conventional excision
Conventional excision
Treatment
Y (after 2 months with lymph node and multiple systemic metastases)
N
Y (after 3 months with locally and lymph node metastasis)
Y (lymph node metastasis)
N
NA
N
N
N
N
N
NA
NA
NA
3 times (since clear margins)
Recurrence
1990
Frouin et al.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
(a)
1991
(b)
(d)
(f)
(c)
(e)
(g)
Figure 6 Immunohistochemical findings in MAC (a-e) and SC (f-g). (a) K77 labels normal eccrine ducts but not tumoural strands in MAC (a K77, 9 10). (b) K77 strongly expressed in inner cells of certain ducts, and slightly in inner cells of cysts in MAC (K77, 9 10). (c) K8 expression restricted to outer cells of islands and cysts but diffused in strands in MAC (K8, 9 10). (d) PHLDA1 pattern with strong expression in strands, and cells lining ducts, moderate in islands containing cysts in MAC (PHLDA1, 9 4). (e) In contrast to K8, K16-labelled inner cells of cysts in MAC (K16, 9 10). (f) K77 expression in luminal cells of ducts in SC (K77, 9 10). (g) PHLDA1 strongly positive in luminal cells of ducts in SC (PHLDA1, 9 10).
entiation and immunohistochemical patterns are more consistent with a follicular origin, but ducts are difficult to explain. The apocrine nature of such ducts has never been demonstrated. Calcifications were found in three of our cases and are wellknown features of many pilar tumours, whereas they are rarer in sweat gland tumours.19,20,21,22 Another argument in favour of a follicular origin is the connexion to follicles seen in near 40% of our cases of MAC. Many immunohistological studies were carried out to clarify histogenesis and for the purpose of differential diagnosis, especially with BCC or desmoplastic trichoepithelioma (dTE). BerEP4 is a marker of normal eccrine secretory and follicular germinative cells, but unlike BCCs, MAC do not express Ber-EP4.23,24 PHLDA1 is a new follicular marker which labels the stem cell of follicular bulge and also eccrine coils. It does not help to differentiate dTE from MAC.24 The keratin expression pattern we observed in MAC is similar to what was previously reported in dTE, suggesting a common bulge-derived origin.25 The absence
JEADV 2015, 29, 1978–1994
of K77 expression (believed to be specific of eccrine excretory ducts)26 in the majority of our cases is a further argument against the eccrine histogenesis. In rare cases (two in this series), expression of K77 in ducts of otherwise classic cases of MAC might be interpreted as a double follicular/eccrine differentiation. In SC, immunohistochemical findings are more consistent with a differentiation towards eccrine apparatus. K77 positivity favours this hypothesis. Langbein et al.12 published the detailed keratin expression pattern of syringomas showing clear-cut eccrine origin. This pattern is similar to what we observed in SC, except for the absence of K8/K18 in syringomas. SC could therefore arise from cells of the secretory and lower excretory portions of the eccrine apparatus. Less than 20 cases of SEDC were reported to date. The term of “squamoid eccrine ductal carcinoma” was proposed by Wong TYet al.,9 for lesions with eccrine ductal differentiation associated with a prominent squamous component. This first short
© 2015 European Academy of Dermatology and Venereology
Frouin et al.
1992
(a)
(b)
(c)
(e)
(d)
(f)
(g)
(h)
Figure 7 Immunohistochemical findings in SEDC. (a–b) K77 labels strongly ducts, (a, 9 4 and b, 9 10). (c) PHLDA1 expressed slightly in superficial islands, predominantly in outer cells. Note the strong positivity in a follicular structure (PHLDA1, 9 10). (d) K10 expression in epidermal suprabasal cells and in tumoural inner cells (K10, 9 4). (e) K16 expressed in epidermoid structures, (e, 9 10). (f) CEA expressed in luminal cells of ducts, emphasizing the ductular component of SEDC (CEA, 9 10). (g) K8 diffusely expressed in deep strands (K8, 9 4). (h) K17 positive in inner cells of islands, and ducts (K17, 9 4).
series concerned patients in their 80s, but patients might be younger.9 Since the review of Terushkin et al. in 2009, we found eight new cases in the literature, including one reported by Sidiropoulos et al. under the name of “syringoid eccrine carcinoma”, but that displayed all criteria of SEDC (see updated review in Table 6).10–11,27–36 Mean age was 66.1 years, (30–91), with a slight male predominance (sex ratio 1.5). In our patients, lesions were exclusively located on head and neck, but previous reports concerned mostly tumours outside the cephalic extremity. Time duration before diagnosis ranged from months to 10 years. Clinically, lesions were described as nodules or plaques with possible erosion or crusting. To the best of our knowledge, the association with organ transplant or immunodeficiency has not been
JEADV 2015, 29, 1978–1994
reported, but two patients had chronic lymphocytic leukaemia.10 Both our patients with organ transplant had already developed SCC years before SEDC, and two patients from the literature also had a past history of non melanoma skin cancers.34,36 Wasserman et al (table 6) and Clarck et al (table 6). SEDC could therefore be added to the list of tumours that can develop in organ transplant patients. SEDC seems to have a worse prognosis than MAC/SC as one of our patients had local recurrences and another died after complete excision could not been achieved. Although the first reports did not mention a particular evolution of SEDC, three recently reported patients developed regional lymph node and systemic metastases.27,29 Additional clinical data and longer follow-up are needed to clarify this point.
© 2015 European Academy of Dermatology and Venereology
Sclerosing sweat duct carcinomas
By definition SEDC exhibits a double pattern, with squamous features predominating in superficial portions and syringomatous eccrine differentiation in the most invasive parts. The squamoid component usually resembles well to moderately well differentiated squamous cell carcinoma. The deep component is evokative of an eccrine origin, with possible perineural invasion. Our cases showed deeper invasion than previously reported, as 72% reached the subcutis (vs. 46%) and 43% the underlying structures (none of previously reported case). The histogenesis of SEDC is also controversial. Certain authors supported an eccrine origin with prominent squamous metaplasia in the ductal structures.9 Others pointed out the similarities with MAC and think SEDC is MAC with squamous features, because of prominent clear cells supposed to be reminiscent of sebaceous differentiation and areas of follicular keratinization.11 Our clinical and immunopathological findings allowed us to rule out this hypothesis. K77 was expressed in ductal structures of all our cases showing that luminal cells of the ductal component are of eccrine origin. We also noticed expression of K6, K16, K17 and K19 in inner structures, as in luminal cells of eccrine ducts and K7, K8 and K18 in the deepest strands, as in secretory cells of eccrine coils. Finally, squamoid differentiation has been reported in benign and malignant eccrine neoplasms.37 All together, our study confirmed the eccrine origin of SEDC.
Conclusion We report thirty cases of sclerosing sweat duct carcinomas composed of three distinct entities with different behaviours and histogenesis. Our study demonstrated that MAC and SC have similar clinical and epidemiological characteristics, although histogenesis differs, mainly follicular in MAC and eccrine in SC. We show arguments for the individualization of SEDC, because of its eccrine origin, more aggressive behaviour and possible occurrence in organ transplant.
Acknowledgements We would like to thank Prs Avril, Dupin, Saiag, Thomas, Drs Audibert, Berthelon-Vachette, Bocquet, Bonnemaison, Bosset, Bouqueau, Brahmi, Brudy, Capitant, Chaix, Christoffersen, Combe, Couder, Cury, Dailloux, Debarbieux, Delachapelle, Devico, Diner, Dumas, Duong, Enache, Espagne, Fahri, Fayard, Foyatier, Gaede, Genvo, Gorin, Gougne-Mahoudeau, GregoireBardel, Hardy, Henryon, Hureau, Janin, Kolb, Lecointre, Lefebvre-Oget, Letessier, Lipowicz, Mayer, Nollez, Olaiwan, Pawin, Pichot, Roth, Runge, Salles, Santoul, Sarfaty, Savary, Seltan, Thiriat, Valantin, Valette, Villaret, Wettervald, Wolff-Ram for clinical information and Mr Peltre for technical support.
References 1 Blake PW, Bradford PT, Devesa SS, Toro JR. Cutaneous appendageal carcinoma incidence and survival patterns in the United States: a population-based study. Arch Dermatol 2010; 146: 625–632.
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