EXTRAORDINARY CASE REPORT
A Unique Case of a Cutaneous Lesion Resembling Mammary Analog Secretory Carcinoma: A Case Report and Review of the Literature Jennifer Albus, BS,* Jacqueline Batanian, PhD,† Bruce M. Wenig, MD,‡ and Claudia I. Vidal, MD, PhD*
Abstract: Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor named for its morphological and genetic similarity to secretory carcinoma of the breast. These tumors are most often found in the parotid gland but have been described in several other mucosal locations of the head and neck. In this case report, a cutaneous lesion most closely resembling MASC was found in a neck mass of a 64-year-old male patient without evidence of a primary salivary gland or oral tumor. The lesion was excised, and the patient remains disease free to date. This case depicts a rare tumor in the skin most closely mimicking MASC and brings additional awareness to dermatopathologists of this tumor. Key Words: mammary analog secretory carcinoma, skin (Am J Dermatopathol 2015;37:e41–e44)
INTRODUCTION Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor, which was originally described by Skalova et al1 in 2010. These tumors are so-named because of their morphological similarity to secretory carcinoma of the breast. The tumors are most commonly located in the parotid gland but have also been described in the submandibular salivary gland, accessory parotid gland, and oral cavity, including the lips, soft palate, buccal mucosa, and the base of the tongue.1 Cutaneous involvement by this tumor has only been described in 2 previous case reports: (1) in the axilla of a 13-year-old female, and (2) detected in a nodule on the flank of a 40-year-old man.2,3 We now report a unique presentation of a tumor most closely resembling MASC in the skin that presented as a dermal mass with slight variation in staining pattern and genetic alterations from the cutaneous lesions previously described. The patient did not have evidence of a salivary gland or oral primary tumor From the *Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, MO; †Department of Pediatrics, Genetics Division, SSM Cardinal Glennon Children’s Medical Center, Saint Louis University Medical Center, Saint Louis, MO; and ‡Department of Pathology, Beth Israel Medical Center, St. Luke’s and Roosevelt Hospitals, New York, NY. The authors declare no conflicts of interest. Reprints: Claudia I. Vidal, MD, PhD, Department of Dermatology and Pathology, Saint Louis University School of Medicine, 1755 South Grand Boulevard, St. Louis, MO 63104 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 4, April 2015
on systemic work-up and was treated successfully with complete excision.
CASE REPORT The patient, an otherwise healthy 64-year-old man, presented with a small (0.5–1.0 cm) mass of the right neck within the anterior triangle and outside the submandibular triangle. A punctum or drainage was not appreciated on examination. The patient reported that the neck lesion had been present “for years,” and was not painful. A specimen was received from a general dermatology office with the clinical impression of “cyst.” Histologically, a multinodular, circumscribed, but unencapsulated epithelial neoplasm within the dermis was identified, showing microcystic, ductal, and solid growth patterns (Figs. 1A–C). Intraluminal homogenous eosinophilic-appearing material was present. The tumor cells showed an eosinophilic granular to vacuolated cytoplasm with vesicular nuclei and inconspicuous to enlarged nucleoli. Focal intranuclear inclusions were appreciated. There was mild cellular pleomorphism and a few but rare mitotic figures. Atypical mitoses and necrosis were not present. Aside from the multinodularity, there was no evidence of neurotropism, lymphvascular invasion, and/or invasion of identifiable cutaneous adnexal structures or surrounding soft tissue. The overlying epidermis was unremarkable. Histochemical stains revealed intraluminal diastase-resistant, periodic acid–Schiff–positive, and mucicarmine-positive material. Intracytoplasmic diastase-sensitive, periodic acid–Schiff–positive material indicative of glycogen was identified. Immunohistochemical (IHC) staining showed the lesional cells to be variably positive for cytokeratins (CK7 and CAM5.2), epithelial membrane antigen (EMA), carcinoembryonic antigen (mono and polyclonal), mammaglobin (Fig. 2A), MUC-1 (Fig. 2B), Ber-EP4, p63 (Fig. 2C), and vimentin and negative for S-100 protein, chromogranin, synaptophysin, BRST-2, and calponin. A proliferation rate assessed by MIB-1 (Ki-67) staining was less than 5% (Fig. 2D). No identifiable salivary gland parenchyma was seen. Based on the light microscopic, histochemical, and IHC findings, the neoplasm was felt to be most consistent with a diagnosis of MASC, despite the S-100 protein negativity. Subsequent fluorescence in situ hybridization analysis of the tumor sections using a dual-labeled break-apart ETV6 probe (Abbott Molecular, Inc, Des Plaines, IL) revealed 1 fusion signal indicating a deletion of 1 copy of ETV6 probe in 25% of cells (Fig. 3). In addition, chromosome microarray analysis of the DNA tumor using array-comparative genome hybridization was performed and revealed additional abnormalities including a deletion in of 13q14.3 involving 3 genes: RNASEH2B, GUCY1B2, and DLEU7 with the latter being considered a novel tumor suppressor gene. After the diagnosis, the patient was seen by his dermatologist and underwent complete excision of the lesion with negative www.amjdermatopathology.com |
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Am J Dermatopathol Volume 37, Number 4, April 2015
Albus et al
FIGURE 1. Histopathologic findings of the tumor. A, Low power magnification showing a multinodular, well-circumscribed, and unencapsulated tumor within the dermis showing solid and ductal growth patterns (Hematoxylin and Eosin, ·40). B, C, High-power magnification showing the solid (B) and ductal (C) growth patterns (Hematoxylin and Eosin, ·400). C, The ductal areas contained homogenous eosinophilic material (Hematoxylin and Eosin, ·400). margins. At this time, he had no lymphadenopathy. He was then referred to an otolaryngologist and was found to have no evidence of disease within his salivary glands or elsewhere.
DISCUSSION MASC is a relatively recently described salivary gland neoplasm with features resembling acinic cell adenocarcinoma (ACA) and low-grade cystadenocarcinoma.1 In the salivary gland and other reported sites, these tumors typically present as a slow-growing painless mass in adults within the average age range of 43–46 years.1,4 Although these tumors tend to present in adults, 2 pediatric cases have been
described in the literature.2,5 The duration of symptoms before presentation has been described to range widely from 2 months to 30 years.1 The documented treatment of MASC is extremely variable. Simple excisions have been performed and radical resections with selective neck dissections. Some patients have also received adjuvant chemotherapy or radiotherapy in their treatment plan.1 Given the rarity of these tumors, they are often treated on a case-by-case basis but are felt to have an overall favorable prognosis, with only rare reports describing positive regional lymph node disease and even less commonly death because of metastatic disease.1 In the literature, the difference in disease-free survival between MASC and ACA has not been
FIGURE 2. A, The tumor was strongly positive for mammaglobin (·600). B, MUC1 highlighted luminal cells in the tumor (·600). C, p63 was positive in the tumor (·200). D, The proliferative index as evidenced by MIB-1 immunostain was low (·40).
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 4, April 2015
FIGURE 3. Fluorescence in situ hybridization of dual-labeled break-apart ETV6 probe showing 1 normal fusion (1F) in 25% of cells (arrows) obtained from paraffin-embedded section slides of the MASC tumor.
found to be statistically significant; therefore, it is recommended that the surgical management of these 2 tumor types should be similar.6 When examined grossly, MASCs are typically solitary, well-circumscribed, but unencapsulated tumors that range from yellow to white or gray and are roughly 1.7–2.5 cm in size.1,7 They may have a visible cystic component.1,8 Histologically, they are composed of uniform cells with eosinophilic cytoplasm and vesicular nuclei arranged in tubular, microcystic, or solid growth patterns. Perineural invasion may be present, but cellular atypia is usually mild, and mitotic figures are rare.9 Typically, MASCs stain positively for mammaglobin and S-100 protein, as well as other markers including CK7, CK8, CK18, and vimentin. Rare tumors, primarily those found intraorally, have been found to be S-100 protein negative.10 Positive staining for EGFR, CAM5.2, CK19, EMA, MUC1, MUC4, STAT5a, and gross cystic disease fluid protein 15 (GCDFP-15) have also been documented.2,9 MASCs are typically negative for basal/myoepithelial markers, including CK14, smooth muscle actin, and CK5/6, with variable expression of p63 and calponin noted in 2 recent cases.9,11 Recently, adipophilin, a marker of cells capable of lipid accumulation, has also been reported to be positive.12 At the genetic level, MASCs contain a balanced translocation: t(12;15) (p12;q25), which fuses 50 ETV6 with 30 NTRK3 in most cases.1 This fusion gene encodes a chimeric tyrosine kinase acting as an oncoprotein directly linked to tumorigenesis in secretory carcinoma of the breast.13 Although documentation of the ETV6 rearrangement is an additional confirmatory test, this test is not widely available, and studies have investigated the use of mammaglobin as a surrogate for the translocation in MASC.14 In a study by Bishop et al,14 mammaglobin staining was found to be 100% sensitive and 92% specific for the presence of the genetic translocation; although positivity of this immunostain alone is insufficient to confirm a diagnosis of MASC, it is a tool that Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Mammary Analogue Secretary Carcinoma in the Skin
can be used to help differentiate MASC from ACA, which are negative for mammaglobin and represent the main tumor that most closely resembles MASC. Other investigations have also failed to identify an IHC marker that can confirm the diagnosis of MASC.7 Our case, in keeping with the diagnosis of MASC, was positive for cytokeratins, vimentin, EMA, MUC1, and importantly mammaglobin. The positivity for p63 in the lesion also fits with recent descriptions of p63 staining in MASC.9 Additionally, the negativity for calponin corresponds with the most commonly described IHC patterns of MASC.11 Although some may argue that the S-100 protein negativity and lack of evidence of the ETV6-NTRK3 translocation is somewhat disconcerting relative to the diagnosis, reports exist of S-100 protein negative tumors10 and tumors that lack the translocation, specifically in the skin.2,3 Interestingly, ETV6 gene was found to be lost in some of the lesional cells in our tumor by fluorescence in situ hybridization. The deletion or amplification of ETV6 gene was previously identified in 2 MASC cases of a large cohort study.15 Chromosome microarray analysis of the tumor also showed a loss in 13q, which signifies further evidence supporting the diagnosis of a MASC-like lesion because losses in 13q have also been reported in secretory breast carcinoma.16 In comparison with the other reported cases with cutaneous involvement, our case has both similarities and differences. Histopathologically, our case is comparable with the exception of the S-100 protein expression.2,3 Likewise, the presence of the ETV6-NTRK3 translocation was not identified in the cutaneous cases previously reported2,3 nor in our case. Unique to our case was the loss of ETV6 in some of the lesional cells and the loss of 13q, both of which have been described in MASC.15,16 The exact progenitor gland of the neoplasm in our case is debatable. The lack of identifiable normal salivary gland parenchyma surrounding the lesion and the existence of nearby normal skin appendage glands favors a cutaneous primary. Additionally, some may argue that the p63 positivity also provides further evidence of a cutaneous primary since this marker has been used by some to differentiate primary from metastatic skin adenocarcinoma.17–19 Still, given the anatomical location of the patient’s tumor and the described origin of MASCs from salivary gland parenchyma, it is conceivable that this patient’s tumor originated from ectopic salivary gland parenchyma located in the skin or from the salivary gland proper where the connection to the salivary gland was not appreciated or ablated. REFERENCES 1. Skalova A, Vanecek T, Sima R, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6–NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34:599–608. 2. Brandt SM, Swistel AJ, Rosen PP. Secretory carcinoma in the axilla probable origin from axillary skin appendage glands in a young girl. Am J Surg Pathol. 2009;33:950–953. 3. Kazakov DV, Vanecek T, Kacerovska D, et al. Mammary-type secretory carcinoma of the skin. Am J Surg Pathol. 2010;34:1226–1227. 4. Griffith C, Stelow E, Saqi A, et al. The cytological features of mammary analogue secretory carcinoma a series of 6 molecularly confirmed cases. Cancer Cytopathol. 2013;121:234–241.
www.amjdermatopathology.com |
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Albus et al
Am J Dermatopathol Volume 37, Number 4, April 2015
5. Rastatter J, Jatana K, Jennings L, et al. Mammary analogue secretory carcinoma of the parotid gland in a pediatric patient. Otolaryngol-Head Neck Surg. 2012;146:514–515. 6. Chiosea SI, Griffith C, Assaad A, et al. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61:387–394. 7. Jung MJ, Song JS, Kim SY, et al. Finding and characterizing mammary analogue secretory carcinoma of the salivary gland. Korean J Pathol. 2013;47:36–43. 8. Bishop J. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands. Head Neck Pathol. 2013;7:35–39. 9. Skalova A. Mammary analogue secretory carcinoma of salivary gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity. Head Neck Pathol. 2013;7:S30–S36. 10. Connor A, Perez-Ordonez B, Shago M, et al. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012;36:27–34. 11. Laco J, Svajdler M Jr, Andrejs J, et al. Mammary analogue secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/ myoepithelial markers (calponin, CD10 and p63 protein). Pathol Res Pract. 2013;209:167–172. 12. Mariano FV, Tavares dos Santos HT, Azanero WD, et al. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour,
and adipophilin can be valuable in its identification. Histopathology. 2013;63:1–10. Li Z, Tognon C, Godinho F, et al. ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Cancer Cell. 2007;12:542–558. Bishop J, Yonescu R, Batista D, et al. Utility of mammaglobin immunohistochemistry as a proxy marker for the ETV6-NTRK3 translocation in the diagnosis of salivary mammary analogue secretory carcinoma. Hum Pathol. 2013;44:1982–1988. Pinto A, Nose V, Fan Y, et al. Mammary Analogue Secretory Carcinoma (MASC) of the Salivary Gland: Revisiting Our Acinic Cell and Poorly Differentiated Carcinomas Using Immunohistochemistry and FISH Studies. Poster presented at: 102nd USCAP Annual Meeting Poster Session III #147; March 5, 2013; Baltimore, MD. Maitra A, Tavassoli F, Albores-Saavedra J, et al. Molecular abnormalities associated with secretory carcinoma of the breast. Hum Pathol. 1999;30: 1435–1440. Ivan D, Hafeez Diwan A, Prieto VG. Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the skin. Mod Pathol. 2005;18:137–142. Ivan D, Nash JW, Prieto VG, et al. Use of p63 expression in distinguishing primary and metastatic cutaneous adnexal neoplasms from metastatic adenocarcinoma to skin. J Cutan Pathol. 2007;34:474–480. Cangelosi JJ, Nash JW, Prieto VG, et al. Cutaneous adnexal tumor with an unusual presentation–discussion of a potential diagnostic pitfall. Am J Dermatopathol. 2009;31:278–281.
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13. 14.
15.
16. 17. 18. 19.
Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
A Unique Case of a Cutaneous Lesion Resembling Mammary Analog Secretory Carcinoma: A Case Report and Review of the Literature Jennifer Albus, BS,* Jacqueline Batanian, PhD,† Bruce M. Wenig, MD,‡ and Claudia I. Vidal, MD, PhD*
Abstract: Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor named for its morphological and genetic similarity to secretory carcinoma of the breast. These tumors are most often found in the parotid gland but have been described in several other mucosal locations of the head and neck. In this case report, a cutaneous lesion most closely resembling MASC was found in a neck mass of a 64-year-old male patient without evidence of a primary salivary gland or oral tumor. The lesion was excised, and the patient remains disease free to date. This case depicts a rare tumor in the skin most closely mimicking MASC and brings additional awareness to dermatopathologists of this tumor. Key Words: mammary analog secretory carcinoma, skin (Am J Dermatopathol 2015;37:e41–e44)
INTRODUCTION Mammary analog secretory carcinoma (MASC) is a rare type of salivary gland tumor, which was originally described by Skalova et al1 in 2010. These tumors are so-named because of their morphological similarity to secretory carcinoma of the breast. The tumors are most commonly located in the parotid gland but have also been described in the submandibular salivary gland, accessory parotid gland, and oral cavity, including the lips, soft palate, buccal mucosa, and the base of the tongue.1 Cutaneous involvement by this tumor has only been described in 2 previous case reports: (1) in the axilla of a 13-year-old female, and (2) detected in a nodule on the flank of a 40-year-old man.2,3 We now report a unique presentation of a tumor most closely resembling MASC in the skin that presented as a dermal mass with slight variation in staining pattern and genetic alterations from the cutaneous lesions previously described. The patient did not have evidence of a salivary gland or oral primary tumor From the *Department of Dermatology, Saint Louis University School of Medicine, Saint Louis, MO; †Department of Pediatrics, Genetics Division, SSM Cardinal Glennon Children’s Medical Center, Saint Louis University Medical Center, Saint Louis, MO; and ‡Department of Pathology, Beth Israel Medical Center, St. Luke’s and Roosevelt Hospitals, New York, NY. The authors declare no conflicts of interest. Reprints: Claudia I. Vidal, MD, PhD, Department of Dermatology and Pathology, Saint Louis University School of Medicine, 1755 South Grand Boulevard, St. Louis, MO 63104 (e-mail: [email protected]). Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Am J Dermatopathol Volume 37, Number 4, April 2015
on systemic work-up and was treated successfully with complete excision.
CASE REPORT The patient, an otherwise healthy 64-year-old man, presented with a small (0.5–1.0 cm) mass of the right neck within the anterior triangle and outside the submandibular triangle. A punctum or drainage was not appreciated on examination. The patient reported that the neck lesion had been present “for years,” and was not painful. A specimen was received from a general dermatology office with the clinical impression of “cyst.” Histologically, a multinodular, circumscribed, but unencapsulated epithelial neoplasm within the dermis was identified, showing microcystic, ductal, and solid growth patterns (Figs. 1A–C). Intraluminal homogenous eosinophilic-appearing material was present. The tumor cells showed an eosinophilic granular to vacuolated cytoplasm with vesicular nuclei and inconspicuous to enlarged nucleoli. Focal intranuclear inclusions were appreciated. There was mild cellular pleomorphism and a few but rare mitotic figures. Atypical mitoses and necrosis were not present. Aside from the multinodularity, there was no evidence of neurotropism, lymphvascular invasion, and/or invasion of identifiable cutaneous adnexal structures or surrounding soft tissue. The overlying epidermis was unremarkable. Histochemical stains revealed intraluminal diastase-resistant, periodic acid–Schiff–positive, and mucicarmine-positive material. Intracytoplasmic diastase-sensitive, periodic acid–Schiff–positive material indicative of glycogen was identified. Immunohistochemical (IHC) staining showed the lesional cells to be variably positive for cytokeratins (CK7 and CAM5.2), epithelial membrane antigen (EMA), carcinoembryonic antigen (mono and polyclonal), mammaglobin (Fig. 2A), MUC-1 (Fig. 2B), Ber-EP4, p63 (Fig. 2C), and vimentin and negative for S-100 protein, chromogranin, synaptophysin, BRST-2, and calponin. A proliferation rate assessed by MIB-1 (Ki-67) staining was less than 5% (Fig. 2D). No identifiable salivary gland parenchyma was seen. Based on the light microscopic, histochemical, and IHC findings, the neoplasm was felt to be most consistent with a diagnosis of MASC, despite the S-100 protein negativity. Subsequent fluorescence in situ hybridization analysis of the tumor sections using a dual-labeled break-apart ETV6 probe (Abbott Molecular, Inc, Des Plaines, IL) revealed 1 fusion signal indicating a deletion of 1 copy of ETV6 probe in 25% of cells (Fig. 3). In addition, chromosome microarray analysis of the DNA tumor using array-comparative genome hybridization was performed and revealed additional abnormalities including a deletion in of 13q14.3 involving 3 genes: RNASEH2B, GUCY1B2, and DLEU7 with the latter being considered a novel tumor suppressor gene. After the diagnosis, the patient was seen by his dermatologist and underwent complete excision of the lesion with negative www.amjdermatopathology.com |
e41
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 4, April 2015
Albus et al
FIGURE 1. Histopathologic findings of the tumor. A, Low power magnification showing a multinodular, well-circumscribed, and unencapsulated tumor within the dermis showing solid and ductal growth patterns (Hematoxylin and Eosin, ·40). B, C, High-power magnification showing the solid (B) and ductal (C) growth patterns (Hematoxylin and Eosin, ·400). C, The ductal areas contained homogenous eosinophilic material (Hematoxylin and Eosin, ·400). margins. At this time, he had no lymphadenopathy. He was then referred to an otolaryngologist and was found to have no evidence of disease within his salivary glands or elsewhere.
DISCUSSION MASC is a relatively recently described salivary gland neoplasm with features resembling acinic cell adenocarcinoma (ACA) and low-grade cystadenocarcinoma.1 In the salivary gland and other reported sites, these tumors typically present as a slow-growing painless mass in adults within the average age range of 43–46 years.1,4 Although these tumors tend to present in adults, 2 pediatric cases have been
described in the literature.2,5 The duration of symptoms before presentation has been described to range widely from 2 months to 30 years.1 The documented treatment of MASC is extremely variable. Simple excisions have been performed and radical resections with selective neck dissections. Some patients have also received adjuvant chemotherapy or radiotherapy in their treatment plan.1 Given the rarity of these tumors, they are often treated on a case-by-case basis but are felt to have an overall favorable prognosis, with only rare reports describing positive regional lymph node disease and even less commonly death because of metastatic disease.1 In the literature, the difference in disease-free survival between MASC and ACA has not been
FIGURE 2. A, The tumor was strongly positive for mammaglobin (·600). B, MUC1 highlighted luminal cells in the tumor (·600). C, p63 was positive in the tumor (·200). D, The proliferative index as evidenced by MIB-1 immunostain was low (·40).
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Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Am J Dermatopathol Volume 37, Number 4, April 2015
FIGURE 3. Fluorescence in situ hybridization of dual-labeled break-apart ETV6 probe showing 1 normal fusion (1F) in 25% of cells (arrows) obtained from paraffin-embedded section slides of the MASC tumor.
found to be statistically significant; therefore, it is recommended that the surgical management of these 2 tumor types should be similar.6 When examined grossly, MASCs are typically solitary, well-circumscribed, but unencapsulated tumors that range from yellow to white or gray and are roughly 1.7–2.5 cm in size.1,7 They may have a visible cystic component.1,8 Histologically, they are composed of uniform cells with eosinophilic cytoplasm and vesicular nuclei arranged in tubular, microcystic, or solid growth patterns. Perineural invasion may be present, but cellular atypia is usually mild, and mitotic figures are rare.9 Typically, MASCs stain positively for mammaglobin and S-100 protein, as well as other markers including CK7, CK8, CK18, and vimentin. Rare tumors, primarily those found intraorally, have been found to be S-100 protein negative.10 Positive staining for EGFR, CAM5.2, CK19, EMA, MUC1, MUC4, STAT5a, and gross cystic disease fluid protein 15 (GCDFP-15) have also been documented.2,9 MASCs are typically negative for basal/myoepithelial markers, including CK14, smooth muscle actin, and CK5/6, with variable expression of p63 and calponin noted in 2 recent cases.9,11 Recently, adipophilin, a marker of cells capable of lipid accumulation, has also been reported to be positive.12 At the genetic level, MASCs contain a balanced translocation: t(12;15) (p12;q25), which fuses 50 ETV6 with 30 NTRK3 in most cases.1 This fusion gene encodes a chimeric tyrosine kinase acting as an oncoprotein directly linked to tumorigenesis in secretory carcinoma of the breast.13 Although documentation of the ETV6 rearrangement is an additional confirmatory test, this test is not widely available, and studies have investigated the use of mammaglobin as a surrogate for the translocation in MASC.14 In a study by Bishop et al,14 mammaglobin staining was found to be 100% sensitive and 92% specific for the presence of the genetic translocation; although positivity of this immunostain alone is insufficient to confirm a diagnosis of MASC, it is a tool that Copyright © 2014 Wolters Kluwer Health, Inc. All rights reserved.
Mammary Analogue Secretary Carcinoma in the Skin
can be used to help differentiate MASC from ACA, which are negative for mammaglobin and represent the main tumor that most closely resembles MASC. Other investigations have also failed to identify an IHC marker that can confirm the diagnosis of MASC.7 Our case, in keeping with the diagnosis of MASC, was positive for cytokeratins, vimentin, EMA, MUC1, and importantly mammaglobin. The positivity for p63 in the lesion also fits with recent descriptions of p63 staining in MASC.9 Additionally, the negativity for calponin corresponds with the most commonly described IHC patterns of MASC.11 Although some may argue that the S-100 protein negativity and lack of evidence of the ETV6-NTRK3 translocation is somewhat disconcerting relative to the diagnosis, reports exist of S-100 protein negative tumors10 and tumors that lack the translocation, specifically in the skin.2,3 Interestingly, ETV6 gene was found to be lost in some of the lesional cells in our tumor by fluorescence in situ hybridization. The deletion or amplification of ETV6 gene was previously identified in 2 MASC cases of a large cohort study.15 Chromosome microarray analysis of the tumor also showed a loss in 13q, which signifies further evidence supporting the diagnosis of a MASC-like lesion because losses in 13q have also been reported in secretory breast carcinoma.16 In comparison with the other reported cases with cutaneous involvement, our case has both similarities and differences. Histopathologically, our case is comparable with the exception of the S-100 protein expression.2,3 Likewise, the presence of the ETV6-NTRK3 translocation was not identified in the cutaneous cases previously reported2,3 nor in our case. Unique to our case was the loss of ETV6 in some of the lesional cells and the loss of 13q, both of which have been described in MASC.15,16 The exact progenitor gland of the neoplasm in our case is debatable. The lack of identifiable normal salivary gland parenchyma surrounding the lesion and the existence of nearby normal skin appendage glands favors a cutaneous primary. Additionally, some may argue that the p63 positivity also provides further evidence of a cutaneous primary since this marker has been used by some to differentiate primary from metastatic skin adenocarcinoma.17–19 Still, given the anatomical location of the patient’s tumor and the described origin of MASCs from salivary gland parenchyma, it is conceivable that this patient’s tumor originated from ectopic salivary gland parenchyma located in the skin or from the salivary gland proper where the connection to the salivary gland was not appreciated or ablated. REFERENCES 1. Skalova A, Vanecek T, Sima R, et al. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6–NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010;34:599–608. 2. Brandt SM, Swistel AJ, Rosen PP. Secretory carcinoma in the axilla probable origin from axillary skin appendage glands in a young girl. Am J Surg Pathol. 2009;33:950–953. 3. Kazakov DV, Vanecek T, Kacerovska D, et al. Mammary-type secretory carcinoma of the skin. Am J Surg Pathol. 2010;34:1226–1227. 4. Griffith C, Stelow E, Saqi A, et al. The cytological features of mammary analogue secretory carcinoma a series of 6 molecularly confirmed cases. Cancer Cytopathol. 2013;121:234–241.
www.amjdermatopathology.com |
e43
Copyright © 2015 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
Albus et al
Am J Dermatopathol Volume 37, Number 4, April 2015
5. Rastatter J, Jatana K, Jennings L, et al. Mammary analogue secretory carcinoma of the parotid gland in a pediatric patient. Otolaryngol-Head Neck Surg. 2012;146:514–515. 6. Chiosea SI, Griffith C, Assaad A, et al. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012;61:387–394. 7. Jung MJ, Song JS, Kim SY, et al. Finding and characterizing mammary analogue secretory carcinoma of the salivary gland. Korean J Pathol. 2013;47:36–43. 8. Bishop J. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands. Head Neck Pathol. 2013;7:35–39. 9. Skalova A. Mammary analogue secretory carcinoma of salivary gland origin: an update and expanded morphologic and immunohistochemical spectrum of recently described entity. Head Neck Pathol. 2013;7:S30–S36. 10. Connor A, Perez-Ordonez B, Shago M, et al. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012;36:27–34. 11. Laco J, Svajdler M Jr, Andrejs J, et al. Mammary analogue secretory carcinoma of salivary glands: a report of 2 cases with expression of basal/ myoepithelial markers (calponin, CD10 and p63 protein). Pathol Res Pract. 2013;209:167–172. 12. Mariano FV, Tavares dos Santos HT, Azanero WD, et al. Mammary analogue secretory carcinoma of salivary glands is a lipid-rich tumour,
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