Eur J Dermatol 2015; 25(5): 483-518
Correspondence
CORRESPONDENCE A rare case of mucinous carcinoma of the skin with multiple organ metastases Mucinous carcinoma of the skin (MCS), which was first reported by Lennox [1], is an adnexal neoplasm considered to originate from the secretory coil of eccrine sweat glands [2]. It is a rare skin malignancy as only approximately 200 cases have so far been reported [3]. Its most common location is the head and neck [4]. Although local recurrences are frequent, only a few cases of distant metastases have been so far reported [5, 6]. We present herein an extremely rare case of MCS metastasizing to the regional lymph nodes and also to distant organs during the 5-year follow-up. A 59-year-old man had noticed a long-lasting painless solitary cutaneous nodule on his chest since about the age of 30 years and was referred to a dermatologist because it had increased in size to 3 cm and had become hard (figure 1A).
A
CEA
B
CK20
C
Th12
L2
D 100
100 CK6
mm
doi:10.1684/ejd.2015.2545
CK7
[L]
[L]
ER
mm
Ki67
Figure 1. A) Clinical aspect of the primary skin tumor: a pale, hard cutaneous nodule, measuring 3 cm in diameter on the chest. B) Hematoxylin-eosin (upper panels) and alcian-blue staining (lower panels) of the primary lesion. Note mucin deposits interspaced by a spiderweb-like fibrous capsule. (scale bar: 100 m). Right panels show a high magnification. C) Immunostaining for CEA, CK6, CK7, CK20, ER, and Ki-67 (from the upper left to lower right). D) Osteolytic changes are seen in the Th12 and L2 vertebral bone with FDG accumulation (white arrows). EJD, vol. 25, n◦ 5, September-October 2015
Histopathological examination of the tumor revealed characteristic large amounts of alcian blue-positive mucin deposits containing small islands of epithelial pleomorphic cells, well-demarcated by a fibrous capsule. The tumor cells were small, basophilic, cuboidal or columnar and contained luminal structures (figure 1B). Immunohistochemical analysis showed positive staining for carcinoembryonic antigen (CEA), cytokeratins 6/7 (CK6/7), and estrogen receptors (ER), but not for CK20 (figure 1C). 10-20% of tumor cells were Ki-67-positive, suggesting a proliferative state (figure 1C). After resection of the cutaneous neoplasm, a thorough whole body examination revealed a left axillary lymph-node swelling without any internal lesion. Since no primary lesion was found except for the skin and lymph node, a preliminary diagnosis of primary MCS and draining lymph-node metastasis was made. The patient subsequently underwent a wide resection of the cutaneous lesion and radical lymph-node dissection of the left axilla. However, metastases to the right axillary lymph-node and the right S10 lung field were detected 1.5 years and 3 years after the initial excision, respectively, and curative surgical resections of them were also carried out. Thereafter, severe lumbago appeared postoperatively, associated with osteolytic changes (from the Th10 to L2 vertebrae) with focal accumulation of 18F FDG, indicating the occurrence of bone metastases and therefore he underwent radiation treatment (total amount of 30 Gy) (figure 1D). There has been no further evidence of disease for six months under treatment with letrozole, bisphosphonate, and denosumab (an anti-RANKL antibody). Primary MCS often recurs locally, while metastasis is rarely encountered, especially to distant organs, therefore, the prognosis is considered relatively favorable [7]. To our knowledge, only two cases with widespread distant metastasis have so far been published [5,6]. Similar to the present case, the tumors of those previous reports were slow-growing and metastases occurred after a long interval of several years. In a meta-analysis of the outcome after surgery, Kamalpour et al. pointed out some factors associated with a poor prognosis, including: large tumor size, long tumor history prior to surgery, and location on the trunk [7]. Our case fulfilled the last two factors. Treatment is very challenging for such cases since there is no established therapy, partly due to the rarity MSC and the few reported metastatic cases [5,6]. By analogy with the treatment of mammary carcinoma, we used an oral aromatase inhibitor, letrozole, because tumor cells expressed ER more abundantly compared to the neighboring sweat glands, thus suggesting the effect of ER signaling on tumor growth, as seen in mammary carcinoma. In addition, bisphosphonate and denosumab were also administered as they were expected to exert inhibitory effects of tumor growth and bone absorption of the metastatic lesions.
483
To cite this article: Tanemura A, Deguchi A, Tanaka A, Kiyohara E, Kishioka A, Katayama I. A rare case of mucinous carcinoma of the skin with multiple organ metastases. Eur J Dermatol 2015; 25(5): 483-518 doi:10.1684/ejd.2015.2545
In fact, the lumbago improved and no further new lesions have developed so far. However, metastatic MCS needs to be investigated more intensively in order to develop an optimal treatment protocol for this tumor.
A
B
C
D
E
Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology Integrated Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan 2 Department of Dermatology, Suita Municipal Hospital
Atsushi TANEMURA1 Ayaka DEGUCHI1 Aya TANAKA1 Eiji KIYOHARA1 Akiko KISHIOKA2 Ichiro KATAYAMA1
F
1. Lennox B, Pearse AG, Richards HG. Mucin-secreting tumours of the skin with special reference to the so-called mixed-salivary tumour of the skin and its relation to hidradenoma. J Pathol Bacteriol 1952; 64: 86580. 2. Headington JT. Primary mucinous carcinoma of skin: histochemistry and electron microscopy. Cancer 1977; 39: 1055-63. 3. Breiting L, Christensen L, Dahlstrom K, Breiting V, Winther JF. Primary mucinous carcinoma of the skin: a population-based study. Int J Dermatol 2008; 47: 242-5. 4. Kazakov DV, Suster S, LeBoit PE, et al. Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast. Am J Surg Pathol 2005; 29: 764-82. 5. Yeung KY, Stinson JC. Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Cancer 1977; 39: 2556-62. 6. Miyasaka M, Tanaka R, Hirabayashi A, Shinohara H, Taira H, Akamatsu T. Primary mucinous carcinoma of the skin: a case of metastasis after 10 years of disease-free survival. Eur J Plast Surg 2009; 32: 189-93. 7. Kamalpour L, Brindise RT, Nodzenski M, Bach DQ, Veledar E, Alam M. Primary cutaneous mucinous carcinoma: a systemic review and meta-analysis of outcomes after surgery. JAMA Dermatol 2014; 150: 380-4.
Figure 1. A) Low power view (hematoxylin and eosin stained slide; original magnification ×40) reveals edema within the upper dermis and thickened collagen bundles throughout the deep reticular dermis. The collagen bundles are arranged parallel to the epidermis. B) Higher power (hematoxylin and eosin stained slide; original magnification ×200) to demonstrate the thickened collagen bundles. In addition, the basophilic material in between the collagen bundles should be noted. C) Orcein stain (original magnification ×200): thickened, coiled elastic bundles as well as foci with loss of elastic tissue. D) Von Kossa stain (original magnification ×200): the basophilic material shows faint positivity. E) The patient’s face reveals a few bullous lesions filled with transparent fluid and several partly encrusted erosions with grey discloration of the skin due to anemia. F) Hand and forearm: largely encrusted excoriations and ulcers due to massive induration of the skin. Contraction of the interphalangeal and metacarpophalangeal joints.
doi:10.1684/ejd.2015.2545
Sclerodermiform porphyria cutanea tarda after torasemide Porphyria cutanea tarda (PCT), a late onset hepatic porphyria, develops when the activity of uroporphyrinogen decarboxylase (Uro-D) is decreased. The acquired type, induced by liver disease or drugs, is common. Typical cutaneous symptoms include skin fragility, vesicles, bullous lesions, atrophic scars, facial hypertrichosis, hyperpigmentation and scarring alopecia [1]. Pseudoscleroderma occurs in 15-18% of patients with an underlying liver disease or in patients on maintenance hemodialysis [2, 3]. To the best of our knowledge, this is the first reported case of sclerodermiform PCT possibly triggered by torasemide in a patient
484
with chronic hepatic and renal failure. We compared it with published sclerodermiform PCT cases (literature review PubMed database 1965-2013). A 71-year-old man presented with general painful sclerodermiform induration of the skin, causing contraction of the interphalangeal and metacarpophalangeal joints (figure 1F), non-healing ulcers on the dorsum of each foot, a few bullous lesions and several encrusted erosions on heliotropic areas (figures 1E-F). Concomitant diseases were grade III renal failure, hepatic cirrhosis, arterial hypertension, type II diabetes and hypertensive heart disease. His daily medication consisted of nebivolol, acetylsalicylic acid, simvastatin, pantoprazol, xipamide, amlodipine/valsartane, sodium hydrogen carbonate and furosemide. The latter had been replaced by torasemide three weeks before the first skin changes were noted. Laboratory tests revealed normochromic anemia (red blood cells 3.47 Mill/L, hemoglobin 11.3 g/dL), elevated ferritin (483 ng/mL) and C-reactive protein (23.8 mg/L), and pathological liver and renal parameters. EJD, vol. 25, n◦ 5, September-October 2015
Correspondence
CORRESPONDENCE A rare case of mucinous carcinoma of the skin with multiple organ metastases Mucinous carcinoma of the skin (MCS), which was first reported by Lennox [1], is an adnexal neoplasm considered to originate from the secretory coil of eccrine sweat glands [2]. It is a rare skin malignancy as only approximately 200 cases have so far been reported [3]. Its most common location is the head and neck [4]. Although local recurrences are frequent, only a few cases of distant metastases have been so far reported [5, 6]. We present herein an extremely rare case of MCS metastasizing to the regional lymph nodes and also to distant organs during the 5-year follow-up. A 59-year-old man had noticed a long-lasting painless solitary cutaneous nodule on his chest since about the age of 30 years and was referred to a dermatologist because it had increased in size to 3 cm and had become hard (figure 1A).
A
CEA
B
CK20
C
Th12
L2
D 100
100 CK6
mm
doi:10.1684/ejd.2015.2545
CK7
[L]
[L]
ER
mm
Ki67
Figure 1. A) Clinical aspect of the primary skin tumor: a pale, hard cutaneous nodule, measuring 3 cm in diameter on the chest. B) Hematoxylin-eosin (upper panels) and alcian-blue staining (lower panels) of the primary lesion. Note mucin deposits interspaced by a spiderweb-like fibrous capsule. (scale bar: 100 m). Right panels show a high magnification. C) Immunostaining for CEA, CK6, CK7, CK20, ER, and Ki-67 (from the upper left to lower right). D) Osteolytic changes are seen in the Th12 and L2 vertebral bone with FDG accumulation (white arrows). EJD, vol. 25, n◦ 5, September-October 2015
Histopathological examination of the tumor revealed characteristic large amounts of alcian blue-positive mucin deposits containing small islands of epithelial pleomorphic cells, well-demarcated by a fibrous capsule. The tumor cells were small, basophilic, cuboidal or columnar and contained luminal structures (figure 1B). Immunohistochemical analysis showed positive staining for carcinoembryonic antigen (CEA), cytokeratins 6/7 (CK6/7), and estrogen receptors (ER), but not for CK20 (figure 1C). 10-20% of tumor cells were Ki-67-positive, suggesting a proliferative state (figure 1C). After resection of the cutaneous neoplasm, a thorough whole body examination revealed a left axillary lymph-node swelling without any internal lesion. Since no primary lesion was found except for the skin and lymph node, a preliminary diagnosis of primary MCS and draining lymph-node metastasis was made. The patient subsequently underwent a wide resection of the cutaneous lesion and radical lymph-node dissection of the left axilla. However, metastases to the right axillary lymph-node and the right S10 lung field were detected 1.5 years and 3 years after the initial excision, respectively, and curative surgical resections of them were also carried out. Thereafter, severe lumbago appeared postoperatively, associated with osteolytic changes (from the Th10 to L2 vertebrae) with focal accumulation of 18F FDG, indicating the occurrence of bone metastases and therefore he underwent radiation treatment (total amount of 30 Gy) (figure 1D). There has been no further evidence of disease for six months under treatment with letrozole, bisphosphonate, and denosumab (an anti-RANKL antibody). Primary MCS often recurs locally, while metastasis is rarely encountered, especially to distant organs, therefore, the prognosis is considered relatively favorable [7]. To our knowledge, only two cases with widespread distant metastasis have so far been published [5,6]. Similar to the present case, the tumors of those previous reports were slow-growing and metastases occurred after a long interval of several years. In a meta-analysis of the outcome after surgery, Kamalpour et al. pointed out some factors associated with a poor prognosis, including: large tumor size, long tumor history prior to surgery, and location on the trunk [7]. Our case fulfilled the last two factors. Treatment is very challenging for such cases since there is no established therapy, partly due to the rarity MSC and the few reported metastatic cases [5,6]. By analogy with the treatment of mammary carcinoma, we used an oral aromatase inhibitor, letrozole, because tumor cells expressed ER more abundantly compared to the neighboring sweat glands, thus suggesting the effect of ER signaling on tumor growth, as seen in mammary carcinoma. In addition, bisphosphonate and denosumab were also administered as they were expected to exert inhibitory effects of tumor growth and bone absorption of the metastatic lesions.
483
To cite this article: Tanemura A, Deguchi A, Tanaka A, Kiyohara E, Kishioka A, Katayama I. A rare case of mucinous carcinoma of the skin with multiple organ metastases. Eur J Dermatol 2015; 25(5): 483-518 doi:10.1684/ejd.2015.2545
In fact, the lumbago improved and no further new lesions have developed so far. However, metastatic MCS needs to be investigated more intensively in order to develop an optimal treatment protocol for this tumor.
A
B
C
D
E
Disclosure. Financial support: none. Conflict of interest: none. 1
Department of Dermatology Integrated Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan 2 Department of Dermatology, Suita Municipal Hospital
Atsushi TANEMURA1 Ayaka DEGUCHI1 Aya TANAKA1 Eiji KIYOHARA1 Akiko KISHIOKA2 Ichiro KATAYAMA1
F
1. Lennox B, Pearse AG, Richards HG. Mucin-secreting tumours of the skin with special reference to the so-called mixed-salivary tumour of the skin and its relation to hidradenoma. J Pathol Bacteriol 1952; 64: 86580. 2. Headington JT. Primary mucinous carcinoma of skin: histochemistry and electron microscopy. Cancer 1977; 39: 1055-63. 3. Breiting L, Christensen L, Dahlstrom K, Breiting V, Winther JF. Primary mucinous carcinoma of the skin: a population-based study. Int J Dermatol 2008; 47: 242-5. 4. Kazakov DV, Suster S, LeBoit PE, et al. Mucinous carcinoma of the skin, primary, and secondary: a clinicopathologic study of 63 cases with emphasis on the morphologic spectrum of primary cutaneous forms: homologies with mucinous lesions in the breast. Am J Surg Pathol 2005; 29: 764-82. 5. Yeung KY, Stinson JC. Mucinous (adenocystic) carcinoma of sweat glands with widespread metastasis. Cancer 1977; 39: 2556-62. 6. Miyasaka M, Tanaka R, Hirabayashi A, Shinohara H, Taira H, Akamatsu T. Primary mucinous carcinoma of the skin: a case of metastasis after 10 years of disease-free survival. Eur J Plast Surg 2009; 32: 189-93. 7. Kamalpour L, Brindise RT, Nodzenski M, Bach DQ, Veledar E, Alam M. Primary cutaneous mucinous carcinoma: a systemic review and meta-analysis of outcomes after surgery. JAMA Dermatol 2014; 150: 380-4.
Figure 1. A) Low power view (hematoxylin and eosin stained slide; original magnification ×40) reveals edema within the upper dermis and thickened collagen bundles throughout the deep reticular dermis. The collagen bundles are arranged parallel to the epidermis. B) Higher power (hematoxylin and eosin stained slide; original magnification ×200) to demonstrate the thickened collagen bundles. In addition, the basophilic material in between the collagen bundles should be noted. C) Orcein stain (original magnification ×200): thickened, coiled elastic bundles as well as foci with loss of elastic tissue. D) Von Kossa stain (original magnification ×200): the basophilic material shows faint positivity. E) The patient’s face reveals a few bullous lesions filled with transparent fluid and several partly encrusted erosions with grey discloration of the skin due to anemia. F) Hand and forearm: largely encrusted excoriations and ulcers due to massive induration of the skin. Contraction of the interphalangeal and metacarpophalangeal joints.
doi:10.1684/ejd.2015.2545
Sclerodermiform porphyria cutanea tarda after torasemide Porphyria cutanea tarda (PCT), a late onset hepatic porphyria, develops when the activity of uroporphyrinogen decarboxylase (Uro-D) is decreased. The acquired type, induced by liver disease or drugs, is common. Typical cutaneous symptoms include skin fragility, vesicles, bullous lesions, atrophic scars, facial hypertrichosis, hyperpigmentation and scarring alopecia [1]. Pseudoscleroderma occurs in 15-18% of patients with an underlying liver disease or in patients on maintenance hemodialysis [2, 3]. To the best of our knowledge, this is the first reported case of sclerodermiform PCT possibly triggered by torasemide in a patient
484
with chronic hepatic and renal failure. We compared it with published sclerodermiform PCT cases (literature review PubMed database 1965-2013). A 71-year-old man presented with general painful sclerodermiform induration of the skin, causing contraction of the interphalangeal and metacarpophalangeal joints (figure 1F), non-healing ulcers on the dorsum of each foot, a few bullous lesions and several encrusted erosions on heliotropic areas (figures 1E-F). Concomitant diseases were grade III renal failure, hepatic cirrhosis, arterial hypertension, type II diabetes and hypertensive heart disease. His daily medication consisted of nebivolol, acetylsalicylic acid, simvastatin, pantoprazol, xipamide, amlodipine/valsartane, sodium hydrogen carbonate and furosemide. The latter had been replaced by torasemide three weeks before the first skin changes were noted. Laboratory tests revealed normochromic anemia (red blood cells 3.47 Mill/L, hemoglobin 11.3 g/dL), elevated ferritin (483 ng/mL) and C-reactive protein (23.8 mg/L), and pathological liver and renal parameters. EJD, vol. 25, n◦ 5, September-October 2015
