Dermatologic surgery

Basosquamous carcinoma and metatypical basal cell carcinoma: a review of treatment with Mohs micrographic surgery Kattie J. Allen1, MD, Mark A. Cappel2, MD, Jill M. Killian3, BS, and Jerry D. Brewer1, MD

1 Division of Dermatologic Surgery, Mayo Clinic, Rochester, MN, 2Department of Dermatology, Mayo Clinic, Jacksonville, FL, and 3Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

Abstract Background Basosquamous carcinoma (BSC) and metatypical basal cell carcinoma (MBCC) are uncommon tumors poorly defined in the literature. Available studies suggest these tumors carry a greater risk of recurrence and metastases than basal cell carcinomas (BCCs) and, in some studies, squamous cell carcinomas. Formal treatment recommendations are not fully established.

Correspondence Jerry D. Brewer, MD Division of Dermatologic Surgery Mayo Clinic 200 First St SW Rochester MN 55905 USA E-mail: [email protected]

Objective To analyze BSC and MBCC separately, evaluate whether they are distinct tumor subtypes, and analyze Mohs micrographic surgery (MMS) efficacy for BSC and

Presented as a poster at the 43rd Mohs College Annual Meeting of the American College of Mohs Surgery, Las Vegas, Nevada, April 28–30, 2011.

one year for both tumor subtypes and were 100% for BSC and 93.8% for MBCC at 5 years. Initial mean sizes were 1.5 cm for BSC and 1.3 cm for MBCC. Approximately 7%

Funding sources: None. Conflicts of interest: None.

MBCC. Methods Retrospective review of medical records and histologic specimens was conducted for 293 patients with 303 biopsy-proven BSCs or MBCCs treated with MMS between 1996 and 2004. In total, 32 BSCs and 128 MBCCs were identified. Surgical and follow-up data were analyzed. Results Kaplan–Meier estimates of recurrence-free survival after MMS were 100% at

represented recurrent tumors at surgery. Of six patients with recurrences, none had known metastatic disease. Limitations Limitations include retrospective design, analysis of only head and neck sites, and small sample sizes. Conclusion BSC and MBCC showed no significant distinguishing characteristics to separate them into two BCC subtypes. Reported recurrence rates for BSC and MBCC are 12–45% with wide local excision; estimated recurrence rates are 4.1% with MMS. Our study showed recurrence-free survival of 95.1% at five years. Hence, MMS is effective in treating these BCC subtypes.

Introduction Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are common, well-recognized, and welldefined cancers of the skin (Fig. 1). Basosquamous carcinomas (BSCs) and metatypical basal cell carcinomas (MBCCs), in contrast, are rare cutaneous cancers with confusing and poorly established definitive histological and behavioral characteristics. BSC was first described in 1910 by MacCormac1 as a specimen that had the coexistence of a BCC and an SCC with no connection between them. Today, much debate still exists about these tumors, with some investigators disputing the tumors’ existence, and others disputing their exact defining characteristics.2–6 Many dermatopathologists interchangeably use BSC and ª 2014 The International Society of Dermatology

MBCC to represent one type of cutaneous malignancy, whereas others separate them into two distinct tumors.4,7,8 In addition, many reports have been published regarding the aggressive nature of these tumors, with suggestion of an increased risk of recurrence and possible metastases.2,9–15 In the present study, we evaluated the efficacy of Mohs micrographic surgery (MMS) regarding local recurrence and metastases in 32 cases of BSC and 128 of MBCC. The two tumor subtypes, BSC and MBCC, were analyzed individually to further evaluate for distinguishing characteristics that would warrant two distinct histologic diagnoses. The two subtypes were also combined into a single group and compared with other typical BCCs. International Journal of Dermatology 2014, 53, 1395–1403



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Methods Data collection and extraction After the study was approved by the Mayo Clinic Institutional Review Board, the electronic patient database was queried for the following keywords: basosquamous carcinoma, metatypical basal cell carcinoma, and Mohs micrographic surgery. The search was limited to the period from January 1996 to December 2004. A total of 1050 cases were retrieved. These cases were reviewed, and only those with a diagnosis of BSC or MBCC on permanent histologic sections that were located on the head and neck and underwent MMS were included, resulting in 303 cases in 293 patients. Slides from the diagnostic biopsy were required for histologic evaluation as part of the inclusion criteria. All electronic charts for each patient were reviewed. The demographic parameters abstracted included age, sex, ethnicity, education level, and history of tobacco use. In International Journal of Dermatology 2014, 53, 1395–1403


Figure 1 Basal cell carcinoma (BCC) and metatypical basal cell carcinoma (MBCC). (a) Keratinizing BCC. (b) Nodular BCC with squamous differentiation. (c) Keratinizing MBCC. (d) Infiltrative MBCC. (e, f) Basosquamous carcinoma. All specimens are stained with hematoxylin and eosin (original magnification 9200)

addition, the patient’s medical history was reviewed for diabetes mellitus, chronic lymphocytic leukemia, organ transplantation, and other forms of immunosuppression. Surgical parameters included tumor location, date of surgery, preoperative size, postoperative size, number of stages, reconstruction method (primary closure, flap, skin graft, or second intention), and whether the tumor was recurrent as defined by the surgeon or the initial evaluating dermatologist who performed the biopsy. Follow-up in number of months and the recurrence (defined as being adjacent to or within a previous surgical scar by the evaluating dermatologist or the MMS surgeon with histologic confirmation) were recorded.

Histologic evaluation All biopsy specimens, which included the initial diagnostic slides, were reviewed by one dermatopathologist (M.A.C.) and the primary investigator (K.J.A.) for the following histologic characteristics: nodular or infiltrative tumor architecture, ª 2014 The International Society of Dermatology

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ulceration, inflammatory infiltrate, reticular dermal or pannicular involvement, perineural invasion, dermal fibrosis, and

Table 1 Histologic definitions of BCC and SCC subtypes

keratinization. In addition, the presence of metatypical cells,

BCCa Aggregations composed of follicular germinative cells that have small, dark monomorphic nuclei and scant cytoplasm Palisade of the peripheral columnar cells within the aggregations Propensity for a cleft to form between aggregations and adjacent stroma SCCa Aggregations made of spinous cells with obvious eosinophilic cytoplasm, pleomorphic nuclei, and other signs of atypia Other signs of altered cornification (dyskeratotic cells and whorls of parakeratosis) within the aggregations MBCC Aggregations composed of nests or strands, or both, of metatypical cellsb Loss of columnar cells arranged in a palisade at the periphery of aggregations Areas of BCC as defined above may also be present in peripheral areas of tumor aggregates, but no SCC Basosquamous carcinoma Presence of BCC and/or metatypical BCC blending into areas of SCC Loss of columnar cells arranged in a palisade at the periphery of aggregations Typical BCC may or may not be present BCC with squamous differentiation Characteristics of a BCC Areas within the tumor aggregates (typically, centrally located) containing squamoid cells (small monomorphic nuclei with scant eosinophilic cytoplasm) Lack of transitional zone and metatypical cells Keratinizing BCC Characteristics of a BCC Abrupt keratinization in the tumor aggregates, usually centrally located Lack of transitional zone and metatypical cells Collision tumor Areas of BCC adjacent to areas of SCC Lack of metatypical cells or transition between two distinct cell types

defined as intermediate cells larger and paler than the basaloid cells of BCC but smaller and less eosinophilic than the spinous cells of SCC, was noted.3,11,16 A transitional zone was defined as an area containing these metatypical cells between a BCC and an SCC.3,6,11,16 The presence of BCC (defined in Table 1), peripheral palisading around the tumor, mucin within the tumor, and invasive SCC (defined in Table 1) were also noted. The tumor was then diagnosed in accordance with the definitions. The BCCs that did not meet the criteria for BSC or MBCC were then used as a control group for comparison.

Statistical methods Recurrence-free survival after surgery for the initial diagnosis was estimated using the Kaplan–Meier method and was compared between the two groups using the log-rank test. All analyses were performed using the SAS version 9.2 software package (SAS Institute Inc., Cary, NC, USA).

Results We reviewed 303 cases with an initial diagnosis of BSC or MBCC in 293 patients. A total of 160 cases in 159 patients were classified as BSC or MBCC based on the definitions shown in Table 1. The other 143 cases were classified based on the definitions in Table 1 as various other tumors, including other subtypes of BCC, SCC, and actinic keratoses. Of the reclassified tumors, 131 were common types of BCC (Table 2). Keratinizing BCCs (n = 20) and BCCs with squamous differentiation (n = 54) were excluded from the BSC and MBCC classifications. Keratinizing BCCs were defined as BCCs with areas of abrupt keratinization, usually located centrally. The BCCs with squamous differentiation were defined as BCCs containing areas of squamoid cells, which usually were centrally located as well. The areas of keratotic or squamoid change were small portions of the tumor in its entirety, and typical BCC characterized the majority of the tumors. In addition, both these tumor subtypes lacked metatypical cells and invasive SCC, and thus they were excluded. Forty-one cases showed classic superficial or nodular BCC characteristics and had no evidence of keratinization, squamatization, or metatypical change. The other 16 BCCs were reclassified as infiltrative or morpheaform and again lacked any keratinization, squamatization, or metatypical changes. The remaining 12 cases were reclassified with diagnoses other than BCC and were SCCs (six cases), SCCs and BCCs (i.e., two completely separate tumors with no areas of connection) (five cases), and irritated trichilemmoma (one case). ª 2014 The International Society of Dermatology

BCC, basal cell carcinoma; MBCC, metatypical basal cell carcinoma; SCC, squamous cell carcinoma. a Data from references 3,4,6,7,10,11, and 13. b Metatypical cells are intermediate cells larger and paler than the basaloid cells of BCC but smaller and less eosinophilic than the spinous cells of SCC.

Among patients with BSC or MBCC at the time of surgery, the median (range) age was 73.8 (35–93) years (Table 3), and 117 men (73.6%) and 42 women (26.4%) comprised the group. Of the 153 patients with documented ethnicity, 100% were Caucasian. Most tumors (94%) occurred on the head, most commonly on the nose (29%). The median follow-up for all patients with BSC or MBCC was 39 months. Histologically, 32 lesions in 31 patients were diagnosed as BSC, and 128 lesions in 128 patients were diagnosed as MBCC (Table 4) in accordance with the definitions listed in the study criteria (see Table 1). A transition marked by the presence of intermediate or metatypical cells and an invasive SCC component were seen in all cases of BSC. A International Journal of Dermatology 2014, 53, 1395–1403



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Table 2 Other BCC types detected in the study Type

No. of cases

BCCs including nodular or superficial Keratinizing BCC BCC with squamous differentiation Morpheaform BCC Infiltrative BCC

41 20 54 1 15

BCC, basal cell carcinoma.

typical BCC component was identified in all but one case, which solely had the transitional area of metatypical cells and invasive SCC. Ulceration was seen in 20 (62.5%) of BSC cases. In the MBCC subgroup, 69 (56.6%) of the cases showed typical features of BCC as defined in Table 1. Eight cases showed evidence of a transition between the characteristic cells of BCC and the metatypical cells.

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Ulceration was present in 47 cases (37.6%), and one patient had signs of perineural invasion. The initial average clinical tumor size (1.4 cm) of the combined BSC and MBCC group before MMS was identical to that of the BCC group. The clinical tumor size of the BSC subgroup was 1.5 cm and of the MBCC subgroup was 1.3 cm. The post-excision defect size was 1.8 cm for the combined group (1.9 cm for BSC and 1.8 cm for MBCC) vs. 1.7 cm for the BCC group. The median number of Mohs layers required for complete removal of these tumors during MMS was one layer in all groups (Table 5). Each layer was taken in standard manner – curettage performed first, followed by the layer removal with a margin determined by the surgeon’s discretion based on clinical presentation. Nine tumors (two BSCs and seven MBCCs) were considered recurrent at the time of initial treatment with MMS at our institution. The initial average clinical size of these tumors was 1.7 cm; the post-excision defect size

Table 3 Characteristics of patients who had the various tumor subtypes


BSC (n = 31)

MBCC (n = 128)

BSC and MBCC (n = 159)

Other BCC subtypes (n = 128)

Age, mean (SD), years Ethnicity Missing/unknown, no. Caucasian Male sex CLL Missing/unknown, no. No Yes Other immunosuppression Missing/unknown, no. No Yes Tobacco use Missing/unknown, no. No Current Former Diabetes mellitus Missing/unknown, no. No Yes Education level Missing/unknown, no. < 12 grade High school graduate Some college College graduate Graduate school

74.2 (10.7)

73.6 (10.4)

73.8 (10.4)

73.3 (12.2)

0 31 (100) 25 (80.6)

6 122 (100) 92 (71.9)

6 153 (100) 117 (73.6)

3 125 (100) 91 (71.1)

6 23 (92.0) 2 (8.0)

27 91 (90.1) 10 (9.9)

33 114 (90.5) 12 (9.5)

30 91 (92.9) 7 (7.1)

5 20 (76.9) 6 (23.1)

28 71 (71.0) 29 (29.0)

33 91 (72.2) 35 (27.8)

30 71 (72.4) 27 (27.6)

6 7 (28.0) 4 (16.0) 14 (56.0)

17 46 (41.4) 9 (8.1) 56 (50.5)

23 53 (39.0) 13 (9.6) 70 (51.5)

18 50 (45.5) 7 (6.4) 53 (48.2)

5 20 (76.9) 6 (23.1)

19 85 (78.0) 24 (22.0)

24 105 (77.8) 30 (22.2)

14 89 (78.1) 25 (21.9)

12 2 6 3 2 6

38 14 32 17 13 14

(10.5) (31.6) (15.8) (10.5) (31.6)

(15.6) (35.6) (18.9) (14.4) (15.6)

50 16 38 20 15 20

(14.7) (34.9) (18.3) (13.8) (18.3)

37 17 25 22 11 16

(18.7) (27.5) (24.2) (12.1) (17.6)

BCC, basal cell carcinoma; BSC, basosquamous carcinoma; CLL, chronic lymphocytic leukemia; MBCC, metatypical basal cell carcinoma. a Values are presented as number and percentage of patients unless specified otherwise. International Journal of Dermatology 2014, 53, 1395–1403

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Table 4 Lesion characteristics of BSC and MBCC cases Characteristica Location Missing/unknown, no. Non-head Nose Cheek Lip Scalp Neck Forehead Ear Other face Initial size, cm, mean (SD) Postop size, cm, mean (SD) No. of Mohs layers, median (25th–75th percentile) Recurrence at time of surgery Missing/unknown, no. No Yes Among those recurrent at time of surgery (n = 9) Initial size, cm, mean (SD) Postop size, cm, mean (SD) No. of Mohs layers, median (25th–75th percentile) Presence of typical BCCb No Yes Presence of transitionb No Yes Presence of invasive SCCb No Yes Perineural invasionb No Yes Keratinizing featuresb No Yes Nodularb No Yes Infiltrativeb No Yes Ulceratedb No Yes

BSC (n = 32)

MBCC (n = 128)

BSC and MBCC (n = 160)

0 1 (3.1) 6 (18.8) 8 (25.0) 0 1 (3.1) 1 (3.1) 8 (25.0) 6 (18.8) 2 (6.3) 1.5 (0.8) 1.9 (0.7) 1 (1–2)

0 8 (6.3) 41 (32.0) 27 (21.1) 8 (6.3) 6 (4.7) 6 (4.7) 19 (14.8) 9 (7.0) 10 (7.8) 1.3 (0.7) 1.8 (0.9) 1 (1–2)

0 9 (5.6) 47 (29.4) 35 (21.9) 8 (5.0) 7 (4.4) 7 (4.4) 27 (16.9) 15 (9.4) 12 (7.5) 1.4 (0.7) 1.8 (0.8) 1 (1–2)

3 27 (93.1) 2 (6.9)

19 102 (93.6) 7 (6.4)

22 129 (93.5) 9 (6.5) 1.7 (0.6) 2.1 (0.8) 2 (2–2)

1 (3.1) 31 (96.9)

53 (43.4) 69 (56.6)

54 (35.1) 100 (64.9)

0 32 (100.0)

112 (93.3) 8 (6.7)

112 (73.7) 40 (26.3)

0 32 (100.0)

121 (100.0) 0

121 (79.1) 32 (20.9)

32 (100.0) 0

110 (99.1) 1 (0.9)

142 (99.3) 1 (0.7)

14 (43.8) 18 (56.3)

86 (69.9) 37 (30.1)

100 (64.5) 55 (35.5)

24 (75.0) 8 (25.0)

88 (72.7) 33 (27.3)

112 (73.2) 42 (26.8)

1 (3.1) 31 (96.9)

9 (7.5) 111 (92.5)

10 (6.6) 142 (93.4)

12 (37.5) 20 (62.5)

78 (62.4) 47 (37.6)

90 (57.3) 67 (26.8)

BSC, basosquamous carcinoma; MBCC, metatypical basal cell carcinoma; postop, postoperative. a Values are presented as number and percentage unless specified otherwise. b Some of the characteristics were left undefined or unknown when the biopsy was too superficial for diagnosis or was a partial sample and tumor extended to the edge.

was 2.1 cm. A median of two Mohs layers was required to achieve clear margins. Median follow-up duration without evidence of recurrence was 58 months in the BSC and MBCC group and in the BCC control group. Recurrences in the combined ª 2014 The International Society of Dermatology

group (Table 6) included the following histologic types of neoplasms: MBCC (n = 1), superficial BCC (n = 1), nodular BCC (n = 3), and micronodular BCC (n = 1). Characteristics of the recurrent tumors are outlined in Table 7. In patients with recurrences, the median time to International Journal of Dermatology 2014, 53, 1395–1403



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Table 5 Mohs layers among BSC, MBCC, and BCC cases Cases, no. (%) Mohs layers, no.

BSC (n = 32)

MBCC (n = 128)

BSC and MBCC (n = 160)

Other BCC (n = 131)

1 2 3 4 5

17 (53.2) 14 (42.7) 0 1 (3.1) 0

85 35 6 2 0

102 49 6 3 0

85 39 5 2 1

(66.4) (27.3) (4.7) (1.6)

(63.8) (30.6) (3.7) (1.9)

(64.9) (29.8) (3.1) (1.5) (0.8)

BCC, basal cell carcinoma; BSC, basosquamous carcinoma; MBCC, metatypical basal cell carcinoma.

recurrence was 47.5 months (range, 30–108 months) in the combined group vs. 40 months (range, 10– 89 months) in the BCC group. No patients had metastatic disease. One patient with documented perineural invasion was lost to follow-up. The Kaplan–Meier estimate of recurrence-free survival at five years was 100% for the BSC subgroup, 93.8% (95% CI, 88.0–99.9) for the MBCC subgroup, 95.1% (95% CI, 90.5–100) in the combined group, and 96.3% (95% CI, 92.3–100) in the BCC group. There was no statistical difference between the three groups (P = 0.42) or between the BSC group and the MBCC group (P =0.19) (Fig. 2). Discussion The medical literature contains much debate regarding the histologic diagnoses of BSC and MBCC and whether these tumors are the same or represent two different tumor subtypes. With a low incidence rate of 1.2–2.7%, much of the previously published literature has been limited to case reports.10,13,17 In addition, the majority of lesions have a nonspecific presentation, and diagnosis is made from histologic evaluation alone, which can be

Table 6 Recurrences by cancer type Cancer type Combined (BSC and MBCC) MBCC Nodular BCC Micronodular BCC Superficial BCC Other BCC Nodular BCC Infiltrative BCC Superficial BCC

Recurrence, no.

1 3 1 1 3 1 1

BCC, basal cell carcinoma; BSC, basosquamous carcinoma; MBCC, metatypical basal cell carcinoma. International Journal of Dermatology 2014, 53, 1395–1403

challenging. Superficial biopsies or partial biopsies may be misdiagnosed as BCC or SCC. Leibovitch et al.16 reported a misdiagnosis in 86.3% of their patients based on initial biopsy performed before MMS. The initial diagnosis in the patients in their study was BCC in 73.7%, SCC in 12.0%, and SCC in situ in 0.6%. Their final histologic diagnosis was based on debulking specimens done before MMS or frozen sections from routine MMS sections, or both. The retrospective review of this study led us to similar findings with a large percentage of tumors being misdiagnosed initially. We started with 303 cases, but after our review, we felt that 143 cases (47.2%) did not satisfy the criteria we had established to be diagnosed as BSC or MBCC. The majority of these were reclassified as keratinizing BCCs or BCCs with squamous differentiation. This discrepancy is likely, in part, because we are attempting to provide distinct criteria to these two previously vague diagnoses, and in doing so, significantly narrows their inclusion criteria. The use of immunohistochemical studies has also aided in providing the correct diagnoses. The stains can help to distinguish the characteristic metatypical or transitional cells from the typical cells in BCCs and SCCs. The use of Ber-EP4, which stains BCCs but not SCCs, has aided the diagnosis of BSC and MBCC and their distinction from SCC (Fig. 3).18–20 After the diagnosis has been made, there is still debate about the appropriate treatment options, which include wide local excision, MMS, sentinel lymph node biopsy, and adjunctive radiotherapy. In addition, with alterations in the cellular morphologic characteristics and expression patterns of these tumors, many previous investigators have suspected an increase in aggressive behavior of these tumors compared with typical BCC. In support of these claims, multiple studies have reported an increased propensity for local recurrence and risk of metastatic potential associated with these tumors.2,9–15 Recurrence rates as high as 12–45% have been reported after wide local excision.3,9,10,13,14,17 More recent studies have documented the ª 2014 The International Society of Dermatology

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Table 7 Characteristics of the post-MMS recurrent cases Patient no. Characteristics







Age at recurrence, years Original diagnosis Location

78 MBCC Right temple

68 MBCC Right alar groove

73 MBCC Left ala

Erythematous scaly patch

Erythematous pearly papule

Ill-defined hyperpigmented plaque

Erythematous papule

Preop size, cm Postop size, cm No. of stages Ulceration Keratinization PNI Diagnosis of recurrence

1.1 9 0.8 1.2 9 0.8 1 No No No NodBCC

0.5 9 0.6 0.5 9 0.6 1 Yes No No MBCC

1.1 9 1.0 1.0 9 1.2 1 No No No MNodBCC

68 MBCC Left postauricular scalp Erythematous pearly keratotic papule 1.8 9 1.4 2.0 9 1.9 2 Yes No No NodBCC

65 MBCC Right forehead

Clinical characteristics

75 MBCC Right lateral cheek Erythematous papule

0.9 9 1.3 1.5 9 1.1 1 No No NAa SFBCC

0.6 9 0.6 1.8 9 1.5 4 No No No NodBCC

MBCC, metatypical basal cell carcinoma; MnodBCC, micronodular basal cell carcinoma; NA, not available; NodBCC, nodular basal cell carcinoma; PNI, perineural invasion; post-MMS, after Mohs micrographic surgery; preop, preoperative; postop, postoperative; SFBCC, superficial basal cell carcinoma. a Biopsy was too superficial to evaluate for PNI.

Figure 2 Recurrence-free survival in BSC, BCC, and MBCC After Mohs micrographic surgery. Kaplan–Meier survival curve shows no statistical difference among the three groups or between the BSC group and the MBCC group. BCC, basal cell carcinoma; BSC, basosquamous carcinoma; MBCC, metatypical basal cell carcinoma

efficacy of MMS for BSC and MBCC, with 5-year recurrence rates reported as 4.1%,16 despite many patients who had signs of perineural invasion16 (Table 8). In the present study, we chose to separate the tumor subtypes BSC and MBCC and analyze them individually and in combination to evaluate distinguishing characteristics or behavioral differences that may exist between them, as well as among cases of other BCCs. No statistically ª 2014 The International Society of Dermatology

significant differences in recurrence or survival were found between the groups in our comparisons. The lack of distinguishing characteristics gives support to the grouping of these two subtypes BSC and MBCC together as one histologic diagnosis. We also would like to draw attention to the common presence of ulceration in these two subtypes, which was present in 62.5% of the BSC cases and 37.6% of the MBCC cases. The presence of ulceration was not statistically significant and did not lead to any change in prognosis, but it does stimulate questions about the role of ulceration in the formation of these tumor subtypes. Does the associated inflammation lead to changes in the stromal environment, which then results in squamatization of the tumor cells? If so, does this result in any significant change in the behavior of the tumor? In our study, no significant behavioral change was noted; however, additional studies comparing BSCs and MBCCs with and without ulceration could help further clarify this notion. In a previous study by de Faria and Navarrete,11 ulceration was noted in nine of 13 tumors, which were called BCCs with areas of SCC. These tumors were composed of mostly BCC, with smaller areas of intermediate cells and occasionally areas of SCC. The areas of SCC were described as being deep in the reticular dermis and striated muscle and were believed to be unrelated to the overlying ulceration. This study also noted increased prevalence of aggressive features, defined by the presence of small cell clusters with spiky outlines and infiltration International Journal of Dermatology 2014, 53, 1395–1403



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Table 8 Literature

review of BSCs treated with Mohs micrographic surgery Study Characteristics

Leibovitch et al.16

Bowman et al.10

No. of cases Definition of BSC

178 Both BCC and SCC with a transition zone

Location Average no. of stages Follow-up Recurrence rate Metastases, no. (%)

Nose (33.1% of cases) 1.7

27 Alternating histologic elements of BCC and SCC in a single tumor; excluded collision lesions and keratinizing BCCs with no SCC Nose 2.0

60 months (51% of cases) 4.1% 2 (2.0)

NA NA 2 (7.4) (at time of surgery)

BCC, basal cell carcinoma; BSC, basosquamous carcinoma; NA, not applicable; SCC, squamous cell carcinoma. International Journal of Dermatology 2014, 53, 1395–1403

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Figure 3 Basal cell carcinoma (BCC) and metatypical basal cell carcinoma (MBCC). Histologic characteristics of specimens comparing hematoxylin– eosin with Ber-EP4. (a, b) BCC with squamous differentiation (a: hematoxylin–eosin; b: Ber-EP4). (c, d) MBCC (c: hematoxylin–eosin; d: Ber-EP4). (e, f) Basosquamous carcinoma (e: hematoxylin–eosin; f: Ber-EP4). All images are original magnification 9100

of cells in cords one and two cells thick in BCCs with areas of SCC in comparison with keratotic BCCs (39%) (P < 0.01). The 5-year recurrence-free survival after MMS of 95.1% in the present study supports the previously reported recurrence rate after MMS of 4.1%.16 Our recurrence rate may be overestimated, in fact, as only one recurrence showed metatypical BCC on biopsy, similar to the previously treated tumor. The other five tumors showed other subtypes of typical BCC, which may lend support to the idea that tumors of the BSC and MBCC subtypes merely reflect underlying microenvironmental factors affecting typical BCC. In addition, our study did not show any evidence of increased aggressive behavior or worse outcomes associated with BSC or MBCC tumors as has been seen in other studies. Our study was limited by its retrospective nature. Systematic documentation of the initial presenting lesion and a standardized method for sampling are missing, which can lead to a sampling error and a misdiagnosis that does not reflect the entire lesion. For example, if only an area ª 2014 The International Society of Dermatology

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of ulceration was biopsied, the lesion may show the majority of metatypical cell changes, whereas a larger sampling may show a predominantly typical BCC with a small area of metatypical cell change. The recurrence rate is also limited by the retrospective nature of this study. We were limited to calling recurrences as any BCC within or adjacent to a surgical scar, as per the initial dermatologist or dermatologic surgeon. No strict criteria were used, thus our recurrence rate may be an overestimation. Our control group was also made from the cases that were rediagnosed from the initial BSC or MBCC group. These tumors were strictly evaluated and did not meet our criteria for BSC or MBCC for this study and fit better into subtypes, as described in Table 1. Because the majority of these other BCCs were keratinizing or had squamous differentiation, our control group could be seen as not a true representation of typical BCC, thus making our comparison of behaviors of BSC and MBCC subtypes to typical BCC not completely accurate. Nevertheless, our study did not show evidence for increased aggressiveness with local or distant metastases in the BSC or MBCC subtypes. Additional studies are necessary to help further define the behavioral pattern of BSC or MBCC in comparison with BCC and SCC. However, given the recurrence rate of 4.9% seen in our study and the previously published recurrence rates of 12–45% seen with wide local excision of these tumors, we support MMS as the treatment of choice for BSC and MBCC. We do not support the use of additional radiologic imaging, adjuvant chemotherapy, or radiation therapy, or sentinel lymph node biopsy for the BSC or MBCC subtypes unless indicated by the clinical presentation (i.e., size or high-risk location) or identification of other high-risk criteria, such as perineural invasion.3,9,10,13,14,17 References 1 MacCormac H. The relation of rodent ulcer to squamous cell carcinoma of the skin. Arch Middlesex Hosp 1910; 19: 172–183. 2 Costantino D, Lowe L, Brown DL. Basosquamous carcinoma: an under-recognized, high-risk cutaneous neoplasm: case study and review of the literature. J Plast Reconstr Aesthet Surg 2006; 59: 424–428. 3 Garcia C, Poletti E, Crowson AN. Basosquamous carcinoma. J Am Acad Dermatol 2009; 60: 137–143. 4 Kelly SC, Kaya G, Ackerman AB. Metatypical basal-cell carcinoma: an analysis in historical perspective. Dermato Pract Concept 2003; 9.

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Mohs surgery for basosquamous carcinoma

Dermatologic surgery

5 Leibovitch I, Huilgol SC, Selva D, et al. Basal cell carcinoma treated with Mohs surgery in Australia. III. Perineural invasion. J Am Acad Dermatol 2005; 53: 458– 463. 6 Maloney ML. What is basosquamous carcinoma? Dermatol Surg 2000; 26: 505–506. 7 Weedon D. Weedon’s Skin Pathology, 3rd edn. Edinburgh: Churchill Livingstone/Elsevier, 2010. 8 Rosai J. Ackerman’s Surgical Pathology, 8th edn. St. Louis, MO: Mosby, 1996. 9 Borel DM. Cutaneous basosquamous carcinoma: review of the literature and report of 35 cases. Arch Pathol 1973; 95: 293–297. 10 Bowman PH, Ratz JL, Knoepp TG, et al. Basosquamous carcinoma. Dermatol Surg 2003; 29: 830–832. 11 de Faria JL, Navarrete MA. The histopathology of the skin basal cell carcinoma with areas of intermediate differentiation: a metatypical carcinoma? Pathol Res Pract 1991; 187: 978–985. 12 Farmer ER, Helwig EB. Metastatic basal cell carcinoma: a clinicopathologic study of seventeen cases. Cancer 1980; 46: 748–757. 13 Martin RC 2nd, Edwards MJ, Cawte TG, et al. Basosquamous carcinoma: analysis of prognostic factors influencing recurrence. Cancer 2000; 88: 1365–1369. 14 Tarallo M, Cigna E, Frati R, et al. Metatypical basal cell carcinoma: a clinical review. J Exp Clin Cancer Res 2008; 27: 65. 15 Volkenstein S, Wohlschlaeger J, Liebau J, et al. Basosquamous carcinoma: a rare but aggressive skin malignancy. J Plast Reconstr Aesthet Surg 2010; 63: e304–e306. Epub 2009 Jul 31. 16 Leibovitch I, Huilgol SC, Selva D, et al. Basosquamous carcinoma: treatment with Mohs micrographic surgery. Cancer 2005; 104: 170–175. 17 Schuller DE, Berg JW, Sherman G, et al. Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis. Otolaryngol Head Neck Surg 1979; 87: 420–427. 18 Beer TW, Shepherd P, Theaker JM. Ber EP4 and epithelial membrane antigen aid distinction of basal cell, squamous cell and basosquamous carcinomas of the skin. Histopathology 2000; 37: 218–223. 19 Jones MS, Helm KF, Maloney ME. The immunohistochemical characteristics of the basosquamous cell carcinoma. Dermatol Surg 1997; 23: 181–184. 20 Kazantseva IA, Khlebnikova AN, Babaev VR. Immunohistochemical study of primary and recurrent basal cell and metatypical carcinomas of the skin. Am J Dermatopathol 1996; 18: 35–42.

International Journal of Dermatology 2014, 53, 1395–1403


Basosquamous carcinoma and metatypical basal cell carcinoma: a review of treatment with Mohs micrographic surgery.

Basosquamous carcinoma (BSC) and metatypical basal cell carcinoma (MBCC) are uncommon tumors poorly defined in the literature. Available studies sugge...
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