- Selected Tumors of the Skin Appendages - Primary vs. Metastasis

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1 - Selected Tumors of the Skin Appendages - Primary vs. Metastasis Napa Valley 2018 Victor G. Prieto, MD, PhD Chair of Pathology UT MD Anderson Cancer Center vprieto@mdanderson.org

2 Napa Valley in May

3 Introduction Threatening field in Pathology Relatively easy distinction between benign and malignant lesions: Circumscription Cytologic features Not so important subclassification, except for same cases Selected lesions Primary vs. metastasis

4 Trichoepithelioma/ Trichoblastoma Solitary: sporadic in childhood or adolescence, flesh-colored, 2-8 mm papule or nodule, face Uncommonly, autosomal dominant Mutations of the region of the Drosophila patched gene (9p21) Differential Dx: BCC

5 Focally cystic pattern Well circumscribed

6 Keratin pearls Cystic areas

7 Central necrosis

8 Rippled morphology More common on the head and neck

9 Follicular differentiation

10 Papillary mesenchymal body Trichoepithelioma / trichoblastoma

11 Dermal proliferation, desmoplastic stroma

12 Some lesions with larger cysts

13 Calcified cysts, rare perineural invasion Desmoplastic trichoepithelioma

14 Older individuals Sun exposure Clefting Myxoid stroma Perineural invasion BCC

15 Hamartomatous BCC (Infundibulocystic) BCC with follicular differentiation, resembling trichoepithelioma Clefting, myxoid stroma Association with basal cell nevus syndrome

16 Large dermal proliferation

17 Papillary mesenchymal body

18 Clefting, myxoid background

19 TE BCC CD34 Diffuse Focal CD10 Stroma Tumor CK20 Scat. Neg Bcl-2 Periph Diff CK20 TE CD10 TE CD34 TE Bcl-2 BCC CK20 BCC CD10 BCC CD34 BCC

20 PHLDA Trichoblastoma PHLDA BCC Courtesy of Dr. Luis Requena

21

22 Key Points TE vs BCC Age and sun damage Cleft and myxoid stroma Mitotic figures / apoptosis Rare papillary mesenchymal bodies CD34, bcl2, CK20, CD10, PHLDA Hamartomatous BCC (mixed features) Re-excision in case of doubt

23 Microcystic Adnexal Ca Solitary lesion, middle-age, upper lip, deeply infiltrative plaque Recurrence Similar lesion in mucosae Mills AM et al. Head and Neck Pathology, 2016; 1-8

24 Lesion on the face

25

26

27 Deep invasion Perineural invasion

28 p63 CK5/6

29 Key Points Female, face Dual differentiation Deep and perineural invasion Locally aggressive

30 Sebaceous Lesions Still controversy (all carcinoma?) Solid or cystic lesions Well circumscribed, lobular Basaloid cells and sebocytes ( scalloping ) Epithelioma (sebaceoma) / adenoma Infiltrative, necrosis, mitotic figures

31 Histologic clues for sebaceous lesions in Muir-Torre syndrome Usually the lesions are hard to classify Sebaceous adenomas or sebaceomas Extraocular location (outside H&N) Multiple lesions Cystic appearance Keratoacanthoma-like architecture

32 Eccrine / Apocrine 40-year-old Caucasian male Benign tumor in his right third digit 4 years ago (unavailable)

33

34

35

36 3 rd recurrence

37 Digital Papillary Adenocarcinoma Originally described in 1987 Variant of sweat gland carcinoma occurring typically on fingers and toes, hands, feet Usually solitary, asymptomatic or accompanied by pain Male predominance (7:1)

38 Digital Papillary Adenocarcinoma Overall recurrence rate 30-40% but is significantly lower (5%) after re-excision or amputation No longer adenoma 14%distal metastases (lung, lymph nodes) Sentinel lymph node biopsy? BRAF-V600E mutation Bell, D., et al. Next-generation sequencing reveals rare genomic alterations in aggressive digital papillary adenocarcinoma. Ann Diagn Pathol 2015; 19(6):

39 Elderly male, face lesion

40 Synaptophysin Chromogranin

41 Eccrine Mucinous Carcinoma (Neuro)Endocrine Type 70 years, W>>M Slow growth Eyelid (inferior) Circumscribed, multinodular Good prognosis Zembowicz et al. Am J Surg Pathol 2005;29:

42 65 F Left eyelid Poorly circumscribed, dermis (subcutis and skeletal muscle)

43 Ducts Hyperchromatic and pleomorphic Extracellular mucin

44 Mucinous Carcinoma Slow growth Face, scalp, axilla Dermal tumor with basophilic mucin and small islands of epithelial cells No dirty necrosis Primary vs. metastatic?

45 Normal pattern CK20 P63 tumor Metastatic GI CDX2

46

47 Adnexal Clear Cell Carcinoma with Comedonecrosis Elderly, M=W Head and neck, scalp Quick growth Erythematous, tan color Solitary papules/nodules (cm) Possibility of recurrence Chaudry and Zembowicz. Arch Pathol Lab Med. 2007;131:

48 Carcinoma with Comedonecrosis Multilobular pattern Squamous and central clear cells Comedonecrosis, NO ducts IHC: EMA, CK17, CEA focal

49

50 CEA

51 Squamoid Ductal Eccrine SCC Solitary dermal nodule Sometimes ulcerated Head, neck, extremities or trunk Middle-aged or elderly Wong TY, Suster S, Mihm MC. Squamoid eccrine ductal carcinoma. Histopathology. 1997;30: van der Horst MP1, Garcia-Herrera A, Markiewicz D, Martin B, Calonje E, Brenn T. Am J Surg Pathol Jun;40:755-60

52 Summary Relatively easy distinction benign vs malignant Not so important subclassification (eccrine, sebaceous) Sebaceous (Muir Torre) Acral lesions Mucinous-neuroendocrine Adnexal clear cell ca. with comedo

53 Cutaneous Metastases 0.7 to 10% of patients with visceral tumors Important topic?: Poor prognosis First sign of disease

54 Cutaneous Metastases Women Breast (60-70%) GI Lung Ovary Men Lung GI Head and neck GU Thyroid, adrenal, endometrium, prostate, mesothelioma Sariya et al. Arch Dermatol 2007; 143: 613

55 Cutaneous Met. Clinical Features Location: Anatomic proximity Chest, abdomen, Neck Scalp Nodules Bullae (Zoster-like) Cellulitis Sclerosis Vasculitis-like

56 Metastasis vs. Primary Clinical Features (Met) Sudden appearance Multiple lesions Previous history Selected anatomic locations (umbilicus) (Primary) Previous, long-standing lesion

57 Primary Cutaneous Eccrine Carcinoma Metastatic Breast Adenocarcinoma

58 Primary Cutaneous Eccrine Carcinoma Metastatic Breast Adenocarcinoma p63

59 Primary Adnexal eccrine carcinoma CK5/6 CK7 Ducts Necrosis Calretinin

60 Marked atypia CK7 TTF1

61 p63 CK20

62 Practical Use of IPOX 1) Confirm diagnosis: - Keratin - CEA (EMA) 2) Primary vs metastatic: - P63 (>25% cells) - D Calretinin - CK5/6 - CK7 3) Origin: - Mammaglobin - CK20 - CDX2, villin - CD TTF1 - CD10 (EMA) - PSA / PSAP 4) Common sense and CPC!

63 Primary vs. Metastatic Summary Important differential diagnosis Clinical and histologic features IHC as an adjunct Most important tool: Telephone

64 Old train Napa Valley Thank you for your attention

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