A Cutaneous Facial Mass Identified as the New Entity Mammary Analogue - - PowerPoint PPT Presentation

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A Cutaneous Facial Mass Identified as the New Entity Mammary Analogue Secretory Carcinoma of Probable Salivary Gland Origin Scott W. Binder, MD Professor and Senior Vice Chair Chief, Dermatopathology Geffen/UCLA Healthcare Case

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A Cutaneous Facial Mass Identified as the New Entity ‘Mammary Analogue Secretory Carcinoma’ of Probable Salivary Gland Origin

Scott W. Binder, MD

Professor and Senior Vice Chair Chief, Dermatopathology Geffen/UCLA Healthcare

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Case Presentation

A 50 year-old man presents with a 7 mm erythematous papule on the right face

  • Developed over a few months
  • Asymptomatic
  • No history of prior neoplasms including salivary gland tumors
  • Lesion located just lateral to nose
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Clinical Impression

“Rule out bug bite”

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Histopathology

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Histopathology

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Histopathology

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Histopathology

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Histopathology

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Histopathology

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Differential Diagnoses

  • Acinic cell carcinoma
  • Apocrine or eccrine sweat duct tumor
  • Mammary analogue secretory carcinoma
  • Benign oncocytic neoplasms
  • Mucoepidermoid carcinoma
  • Metastasis from a visceral primary
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Outside Special Stains

S-100 EMA CK 7 CK 20 p63 Mucicarmine

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Additional Immunohistochemistry

Mammaglobin CEA CK 5/6 Thyroglobin TTF-1 PSA Ki67

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Diagnosis

  • Mammary Analogue Secretory Carcinoma (MASC)
  • ? Primary salivary gland origin v. primary cutaneous tumor
  • Rule out metastasis
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Background

  • MASC first described in 2010 by Skalova et al.
  • Morphologic overlap between acinic cell carcinoma and

secretory carcinoma of the breast

  • Tumors affect all ages (range 14-77), slightly male-predominant
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MASC

  • Presents as slowly growing mass,
  • ften near parotid gland
  • No evidence of primary cutaneous
  • rigin, as of yet
  • Most treated with non-radical

excision +/-radiotherapy

  • Cases of lymph node metastases,

local recurrences, low mortality

Chiosea et al, Histopathology 2012

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Histology of MASC

  • Unencapsulated, lobulated
  • Intercalated duct cells in tubular, microcystic, papillary patterns
  • Lumina with ample “bubbly” secretions (mucicarmine +)
  • Absence of serous acinar granules
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Immunohistochemistry of MASC

Staining

  • Usually positive
  • S100
  • CK7
  • Vimentin
  • Often positive
  • EMA
  • GCDFP
  • Mammaglobin
  • Negative
  • CK5/6, CK20
  • P63, TTF-1, PSA, Thyroglobulin

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Immunohistochemistry of most apocrine tumors

  • Cytokeratin 5/6+, p63+
  • S100+/-, cytokeratin 7+
  • Mammaglobin +/-, EMA+ (patchy, highlights ducts)
  • CEA+, GCDFP 15+/-

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Key Differential Diagnoses of MASC

Diagnosis Key Cytomorphologic Features Ancillary Testing Features Benign oncocytic neoplasms (oncocytoma,

  • ncocytic cystadenoma,

Warthin tumor) Lack vacuolated cytoplasm, more cohesive S-100 negative, anti- mitochondrial antibody positive Acinic cell carcinoma Usually lacks mucin PAS-D+ cytoplasmic granules, DOG-1 strongly positive, mammaglobin negative Mucoepidermoid carcinoma Epidermoid differentiation p63 positive, S100 negative, MAML2 translocation Metastatic carcinoma High grade nuclei, many show necrosis Staining variable

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Fusion Gene

  • Almost all MASC had fusion gene ETV6-NTRK3

Normal Cells No ETV6 Split Signals Abnormal ETV6 split signals

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Clinical Course

  • Patient had neoplasm completely excised by the ENT service
  • Work-up for primary underlying neoplasm is on-going and

imaging studies are negative for primary salivary gland tumor

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Summary

  • MASC is likely an under-recognized diagnosis and can present a

diagnostic pitfall, easily being confused with a primary adnexal tumor given that it is a newly-described entity and too bland to be immediately interpreted as a metastasis or recurrence. The

  • rigin of this particular tumor is still uncertain, as no salivary

gland primary has been detected in this patient.

  • Immunohistochemical stains for S100, CK7, p63, cytokeratin 5/6,

mammaglobin, and identification of the ETV6-NTRK3 fusion gene would be required to completely evaluate tumors of this type

  • ? Primary cutaneous/subcutis MASC v. unusual primary apocrine

sweat duct tumor (solid and cystic hidradenoma)

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Cutaneous Metastases v. Adnexal Primary Carcinoma: A Practical Approach

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Cutaneous Metastases

  • Clinical Considerations
  • Mean age at presentation is 62
  • Most common primary tumors
  • Lung

30%

  • Melanoma

18%

  • G.I. Tract

14%

  • Breast

5%

  • Lymphoma

5%

  • In approximately 10% of cases, the primary is unknown
  • Histologic Types
  • Adenocarcinoma

40%

  • Melanoma

15%

  • Squamous carcinoma

15%

  • Other

30%

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Histopathologic Characteristics of Metastases
  • Tumor growth often concentrated in the deep dermis - “bottom

heavy” appearance

  • Sparing of epidermis common
  • Ulceration and pagetoid spread rarely noted (colonic and melanoma)
  • Tumor necrosis sometimes present
  • Lymph/vascular invasion sometimes observed
  • High grade tumor cells with numerous mitoses

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Immunohistochemical Considerations
  • Battery may include
  • Cytokeratin 7
  • Cytokeratin 20
  • S-100
  • MART-1/Melan-A/MITF or SOX-10
  • PSA
  • TTF-1
  • ER/PR/Her-2-neu
  • CDX-2
  • Cytokeratin 5/6, p63*

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Recent studies have shown that CK5/6 and p63 may help

distinguish primary adnexal neoplasms (CK5/6+/p63+) from most metastatic carcinomas (CK5/6-/p63-)

  • P63 especially helpful
  • D2-40 not been especially helpful in my lab

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46 yo F with history of breast cancer x7 years

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Histopathology

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Histopathology

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Histopathology

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IHC Results

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CK7

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IHC Results

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ER

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IHC Results

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HER2/neu

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IHC Results

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CK5/6

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IHC Results

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P63

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68 yo M w paranasal mass present x 1 yr – rapid recent growth

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Histopathology

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Histopathology

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Histopathology

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IHC Results

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CK5/6

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IHC Results

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p63

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Impossible to reliably distinguish primary or metastatic

eccrine/apocrine tumors from cutaneous metastases

  • f breast carcinomas, especially apocrine or mucinous

types

  • Immunohistochemical Staining of Breast v. Metastases
  • ER (estrogen receptor)
  • PR (progesterone receptor)
  • GCDFP-15 (gross cystic disease fluid protein)
  • CEA
  • Her-2-neu
  • None of these may reliably separate primary sweat

duct tumors from breast metastases

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Aberrant staining of metastases
  • Technical
  • Antibody
  • Technique
  • Therapeutic effect – chemo and/or radiation/immune

modulators

  • Tumor metastases may have different immuno

phenotypes than the primary

  • Tumors don’t always read the books
  • Another tumor/primary is responsible for the aberrant

staining

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Cutaneous Metastases v. Primary Adnexal Carcinoma

  • Take Home
  • H&E considerations and clinical information most

important for diagnostic purposes

  • Immunohistochemistry stains are useful ancillary studies,

especially cytokeratin 5/6 and p63 but be careful as these may lead you astray

  • Be sure to eliminate the possibility of a basal cell

carcinoma demonstrating unusual growth patterns

  • Always think of the possibility of a primary adnexal CA in

the appropriate clinical and histologic context

  • Occasional inability to differentiate a primary adnexal CA

from a visceral metastasis

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References

  • Saliva A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH,

Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M. 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 May;34(5):599-608.
  • Griffith C, Seethala R, Chiosea SI. Mammary analogue secretory carcinoma: a new twist to the diagnostic

dilemma of zymogen granule poor acinic cell carcinoma. Virchows Arch. 2011 Jul;459(1):117-8.

  • Fehr A, Löning T, Stenman G. Mammary analogue secretory carcinoma of the salivary glands with ETV6-

NTRK3 gene fusion. Am J Surg Pathol. 2011 Oct;35(10):1600-2.

  • Rastatter JC, Jatana KR, Jennings LJ, Melin-Aldana H. Mammary analogue secretory carcinoma of the

parotid gland in a pediatric patient. Otolaryngol Head Neck Surg. 2012 Mar;146(3):514-5.

  • Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I. 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 Jan;36(1):27-34.

  • Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue

secretory carcinoma of salivary glands. Histopathology. 2012 Sep;61(3):387-94.

  • Griffith CC, Stelow EB, Saqi A, Khalbuss WE, Schneider F, Chiosea SI, Seethala RR. The cytological features
  • f mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases. Cancer
  • Cytopathol. 2013 May;121(5):234-41.
  • Bishop JA. 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 Mar;7(1):35-9.
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SLIDE 47

References

  • Jung MJ, Song JS, Kim SY, Nam SY, Roh JL, Choi SH, Kim SB, Cho KJ. Finding and characterizing

mammary analogue secretory carcinoma of the salivary gland. Korean J Pathol. 2013 Feb;47(1):36- 43.

  • Hwang MJ, Wu PR, Chen CM, Chen CY, Chen CJ. A rare malignancy of the parotid gland in a 13-

year-old Taiwanese boy: case report of a mammary analogue secretory carcinoma of the salivary gland with molecular study. Med Mol Morphol. 2013 Aug 18.

  • Knezevich SR, Garnett MJ, Pysher TJ, et al. ETV6-NTRK3 gene fusions and trisomy 11 establish a

histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998;15:5046–5048.

  • Makretsov N, He M, Hayes M, et al. A fluorescence in situ hybridization study of ETV6-NTRK3

fusion gene in secretory breast carcinoma. Genes Chromosomes Cancer. 2004;40:152–157.

  • Rastatter JC, Jatana KR, Jennings LJ, Melin-Aldana H. Mammary analogue secretory carcinoma of

the parotid gland in a pediatric patient. Otolaryngol Head Neck Surg. 2012 Mar;146(3):514-5.

  • Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I. Mammary analog secretory carcinoma
  • f 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 Jan;36(1):27-34.

  • Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary

analogue secretory carcinoma of salivary glands. Histopathology. 2012 Sep;61(3):387-94.

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SLIDE 48

References

  • Griffith CC, Stelow EB, Saqi A, Khalbuss WE, Schneider F, Chiosea SI, Seethala RR. The

cytological features of mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases. Cancer Cytopathol. 2013 May;121(5):234-41.

  • Bishop JA. 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 Mar;7(1):35-9.

  • Jung MJ, Song JS, Kim SY, Nam SY, Roh JL, Choi SH, Kim SB, Cho KJ. Finding and characterizing

mammary analogue secretory carcinoma of the salivary gland. Korean J Pathol. 2013 Feb;47(1):36-43.

  • Hwang MJ, Wu PR, Chen CM, Chen CY, Chen CJ. A rare malignancy of the parotid gland in a

13-year-old Taiwanese boy: case report of a mammary analogue secretory carcinoma of the salivary gland with molecular study. Med Mol Morphol. 2013 Aug 18.

  • Knezevich SR, Garnett MJ, Pysher TJ, et al. ETV6-NTRK3 gene fusions and trisomy 11

establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 1998;15:5046–5048.

  • Makretsov N, He M, Hayes M, et al. A fluorescence in situ hybridization study of ETV6-NTRK3

fusion gene in secretory breast carcinoma. Genes Chromosomes Cancer. 2004;40:152–157.