10/24/2019
What’s a gland like you doing in a place like this? A practical approach to cutaneous adnexal neoplasms Hafeez Diwan, MD, PhD Departments of Pathology & Immunology and Dermatology Baylor College of Medicine
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Conflict of interest
• None
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Disclosures
• I have nothing to disclose
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Is the adnexal neoplasm glandular? And if so, where is it located? • Hands and Feet: Digital papillary adenocarcinoma
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Digital Papillary Adenocarcinoma
• Solitary • Fingers/toes/palms/soles • Recurrence/metastases
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3 Points about digital papillary adenocarcinoma • 1. Atypia doesn’t matter – if there is no atypia, it doesn’t mean that it isn’t digital papillary adenocarcinoma
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3 Points about digital papillary adenocarcinoma • 1. Atypia doesn’t matter – if there is no atypia, it doesn’t mean that it isn’t digital papillary adenocarcinoma • 2. How high can the glandular lesion go up the extremity? • Example of one case that occurred on the thigh? (Alomari A, Douglas S, Galan A, Narayan D, Ko C. Atypical Presentation of digital papillary adenocarcinoma (abstract) J Cutan Pathol. 2014;41:221)
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3 Points about digital papillary adenocarcinoma (cont’d) • 3. What if you don’t see glands • Hidradenoma on hands and feet • Hunt for a gland? If you see a gland, then what? • Probably best to err on the side of caution and say that a digital papillary adenocarcinoma is not ruled out
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3 Points about digital papillary adenocarcinoma (cont’d) • 3. What if you don’t see glands • Hidradenoma on hands and feet • Hunt for a gland? If you see a gland, then what? • Probably best to err on the side of caution and say that a digital papillary adenocarcinoma is not ruled out • P63? • Positive in basal layer of digital papillary adenocarcinoma vs. throughout in hidradenoma?
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Digital papillary adenocarcinoma – quasi- controversial aspects • Previously used to be called aggressive, till the “aggressive” was dropped • Now, some authors have suggested they may not be that aggressive (because a myoepithelial layer is present, so is it really adenocarcinoma in situ?) • However, as there is high potential for metastasis, with a local recurrence rate of 50% and a 14% rate of metastasis, most commonly to the lungs (70%), and since atypia is no guide to how these lesions will behave, it is probably best to call glandular adnexal neoplasms on hands and feet adenocarcinoma
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Is it on or near the eyelid and does it have a cribriform appearance
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Endocrine mucin-producing sweat gland carcinoma
• EMPSGC is histologically and immunohistochemically similar to solid papillary carcinoma of breast/ endocrine ductal carcinoma in situ, which is considered a precursor lesion to mucinous carcinoma
• EMPSGC is believed to be a precursor of cutaneous mucinous carcinoma (MC)
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Histology
• Cystic, partially cystic and/or solid tumor nests
• Low-grade cytology
• Neuroendocrine differentiation
• Mucin production
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Immunohistochemical studies
• Expression of a specific neuroendocrine marker is required for the diagnosis of EMPSGC.
Positive Staining Negative Staining ER CK20 PR CK7 LMWCK (CAM 5.2) CD56/synaptophysin/chromogranin Myoepithelial cells: SMA, p63, calponin (Discordant staining between authors)
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EMPSGC Mucin production is typically non- copious No infiltrative growth pattern
Invasive mucinous carcinomas Nests and strands of cells infiltrating the dermis Advanced cases: clusters of tumor cells floating in large stromal pools of mucin
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Mucinous Eccrine Carcinoma
• Face/scalp/axilla/trunk • Recurrence • Metastasis
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Does it have a cribriform appearance and is well-circumscribed? Cutaneous Cribriform Carcinoma
J-D Wu et al. Indian J Dermatol Venerol Leprol. 2018; 84(5):569-572: Neck of 26 year-old female
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Cutaneous cribriform carcinoma
• S100, C-kit positive; calponin, p63, SMA negative (helps distinguish from a tubular adenoma) – DP Arps et al. J Cutan Pathol. 2015; 42:379-387: • 6 cases (3 leg, 2 arm, 1 elbow) • 5/6 had lymphoid aggregates • All had desmoplastic stroma • Circumscribed (unlike adenoid cystic carcinoma ACC, which is also C-kit & S100 positive; but ACC is not circumscribed and is neurotropic)
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YG Xu et al. J Oncol. 2010 Apr 7. doi: 10.1155/2010/469049 Pathology Outlines (GA Tranesh); Photo: Dr. Mark Wick
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Beware of adenoid cystic carcinoma on the lower portion of the face! • It could be salivary gland adenoid cystic carcinoma extending into the skin.
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Does it have prominent eosinophilic secretions? Cutaneous secretory carcinoma
L Requena & O Sangueza. Cutaneous adnexal neoplasms. Springer, 2018 No particular anatomic site Positive for S100, EGFR, p63, calponin, SMA Negative for CEA, p53, Her-2 neu Positive for ETV6-NTRK3 (like breast secretory carcinoma) 40
L Requena & O Sangueza. Cutaneous adnexal neoplasms. Springer, 2018
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Does it have squamous or squamoid appearing areas with ducts?
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van der Horst MPJ, Brenn T. Surgical Pathology 10: 383– 397, 2017
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van der Horst MPJ, Brenn T. Surgical Pathology 10: 383– 397, 2017
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van der Horst MPJ, Brenn T. Surgical Pathology 10: 383– 397, 2017
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Squamoid eccrine carcinoma
• Head and neck of elderly males • Most common: face • High recurrence • Can metastasize (most often to lymph nodes, but elsewhere as well) • Complete excision and clinical follow-up
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Does it remind you of a rabbit burrow?
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THE RABBIT BURROW
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Syringocystadenoma Papilliferum
• Scalp and forehead • Other sites possible • Associated with NS • Coexistent BCC also possible
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Does it remind you of a maze
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THE MAZE
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Hidradenoma papilliferum with lactational changes
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Primary vs metastatic
• Primary – p63, p40, CK15, calretinin, D2-40, CK5/6 • Primary – look for a benign component; if there is one, it might be primary • Caveats • Triple negative BCC and lung CA can be p63 positive • Calretinin will be positive in metastatic mesothelioma • Apocrine carcinoma is p63 negative
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Primary vs metastatic
• What about clear cells as in hidradenocarcinoma? • Ducts will be EMA/CEA, tumor itself will be LMWK and S100 • Renal cell carcinoma can have clear cells – but PAX8, CD10, RCC can help • Thyroid carcinoma can have clear cells – but TG and TTF-1 can help
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Sebaceous neoplasms – to mismatch or not to mismatch • High false positives • Do it if the lesions look cystic or “complicated” or if there is a keratoacanthoma with sebaceous differentiation, or • If there are multiple lesions • If there is a family history
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Is it sebaceous or not?
• EMA (also SCC, but not BCC) • Adipophilin • Factor 13a • AR (but BCC can be positive) • NOT USEFUL ONES: • BerEP4 (BCC and sebaceous) • Cam5.2 (BCC, SCC, and sebaceous) • CK7 (BCC, SCC, and sebaceous)
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Danialan R, Mutyambizi K, Aung PP, Prieto VG, Ivan D. J Clin Pathol 2015;68: 992–1002.
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Tjarks et al., JCP 45: 1-7, 2018
Factor 13a clone AC-1A1
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Tjarks et al., JCP 45: 1-7, 2018
Factor 13a clone AC- 1A1)
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What about focal sebaceous differentiation?
• If it looks like SCCIS, or BCC, or invasive SCC with focal sebaceous differentiation, then it is probably just focal sebaceous differentiation rather than a sebaceous neoplasm.
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It might be benign, if it weren’t malignant
• Can you see the bottom of the lesion? • Can you see the entire lesion? • Is the border infiltrative?
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• 80 year-old male with left arm lesion – 11/30/12
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• 2 months later, 1/28/13, the lesion was re-excised
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P16
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• 87 year-old, center forehead lesion, 8/17/2012
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• Nearly a year and a half later, re-biopsy
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What might help in distinguishing benign from malignant sebaceous neoplasms • P53, Ki-67 – both increased in sebaceous carcinoma
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Related concept – what’s the architecture of the lesion? • Circumscribed or infiltrative? • Even if it doesn’t look too atypical, infiltrativeness trumps atypia
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Is there cytologic atypia?
• If the border is infiltrative, then lack of atypia doesn’t matter much • But cytologic atypia can be helpful
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Porocarcinoma
• Local recurrence • Metastasis – both regional and distant
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Eccrine Carcinoma
• Rare • Scalp/extremities/trunk • Local recurrence
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Malignant pilomatricoma
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Trichoepithelioma vs. BCC vs. MAC vs syringoma
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BCC vs. TE
• Bcl2 – BCC (also desmoplastic TE); peripheral cells in TE • BerEP4 – BCC (also desmoplastic TE) • CK 20 – TE • CD34 – TE stroma • CD10 – TE stroma; CD10 – BCC tumor • AR – BCC – But some studies show AR in TE • ?p75 in BCC and desmoplastic TE
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CD34
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CK20
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Desmoplastic Trichoepithelioma
• Face • Solitary • Very important differential diagnosis
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Syringoma
• Multiple, lower eyelids and cheeks • Adolescent females • Clear cell variant in DM • More common in Down
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Keratocysts and eccrine components = think of MAC
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Microcystic Adnexal Carcinoma
• Face – particularly upper lip; other sites also possible • Locally aggressive • Always think of it in incomplete biopsies • Beware of frozen sections!
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MAC vs DTE vs BCC infiltrative
• MAC vs DTE – CEA, CD23, PHLDA-1, CK20 • MAC vs infiltrative BCC – CEA, CD23, CK15
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What’s in a name?
• Which adnexal structure does it seem to be arising from?
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FI
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Alsaad KO, Obaidat NA, Ghazarian D Skin adnexal neoplasms—part 1: An approach to tumours of the pilosebaceous unit Journal of Clinical Pathology 2007;60:129-144.
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Whole lot of adnexal going on
• Tumors with mixed lineages • Hair tumors with all parts of hairs
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Whole lot of adnexal going on
• Tumors with mixed lineages • Hair tumors with all parts of hairs • Don’t get all tangled up in it – give it the best name you can
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Alkhalidi HMS, Alhumaidy AA. Cystic panfolliculoma of the scalp: Report of a very rare case and brief review. Indian Journal of Pathology and Immunology, 2013; 56: 437-9
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@JMGardnerMD Follow Follow @JMGardnerMD More Folliculosebaceous cystic hamartoma. Sebaceous glands & follicles empty into dilated cyst. Dense surrounding stroma. #Pathology #dermpath
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DS Cassarino et al. JCP 2006; 33: 261-279
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FOLLICLE
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FOLLICLE
= Follicular SCC
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Follicular (or infundibular) SCC
• Low risk or indeterminate or aggressive • Arise from the follicle – upper portion (infundibulum) • Sun-damaged skin, especially face • Elderly
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In summary…
• Glandular lesions are important, especially on certain locations • The lower border of a lesion is critical to evaluate • If a tumor is infiltrative, it’s best to call malignant (or atypical) even if there is no cytologic atypia • But cytologic atypia is important too • Judicious use of immunos may be helpful • Adnexal granularity is useful within limits – does it matter if you call it folliculosebaceous hamartoma or sebaceous trichofolliculoma?
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