- 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
Napa Valley in May
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
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
Focally cystic pattern Well circumscribed
Keratin pearls Cystic areas
Central necrosis
Rippled morphology More common on the head and neck
Follicular differentiation
Papillary mesenchymal body Trichoepithelioma / trichoblastoma
Dermal proliferation, desmoplastic stroma
Some lesions with larger cysts
Calcified cysts, rare perineural invasion Desmoplastic trichoepithelioma
Older individuals Sun exposure Clefting Myxoid stroma Perineural invasion BCC
Hamartomatous BCC (Infundibulocystic) BCC with follicular differentiation, resembling trichoepithelioma Clefting, myxoid stroma Association with basal cell nevus syndrome
Large dermal proliferation
Papillary mesenchymal body
Clefting, myxoid background
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
PHLDA Trichoblastoma PHLDA BCC Courtesy of Dr. Luis Requena
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
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
Lesion on the face
Deep invasion Perineural invasion
p63 CK5/6
Key Points Female, face Dual differentiation Deep and perineural invasion Locally aggressive
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
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
Eccrine / Apocrine 40-year-old Caucasian male Benign tumor in his right third digit 4 years ago (unavailable)
3 rd recurrence
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)
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): 381-384.
Elderly male, face lesion
Synaptophysin Chromogranin
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;29:1330 1339
65 F Left eyelid Poorly circumscribed, dermis (subcutis and skeletal muscle)
Ducts Hyperchromatic and pleomorphic Extracellular mucin
Mucinous Carcinoma Slow growth Face, scalp, axilla Dermal tumor with basophilic mucin and small islands of epithelial cells No dirty necrosis Primary vs. metastatic?
Normal pattern CK20 P63 tumor Metastatic GI CDX2
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;131:1655 1664
Carcinoma with Comedonecrosis Multilobular pattern Squamous and central clear cells Comedonecrosis, NO ducts IHC: EMA, CK17, CEA focal
CEA
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;30:288 293 van der Horst MP1, Garcia-Herrera A, Markiewicz D, Martin B, Calonje E, Brenn T. Am J Surg Pathol. 2016 Jun;40:755-60
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
Cutaneous Metastases 0.7 to 10% of patients with visceral tumors Important topic?: Poor prognosis First sign of disease
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
Cutaneous Met. Clinical Features Location: Anatomic proximity Chest, abdomen, Neck Scalp Nodules Bullae (Zoster-like) Cellulitis Sclerosis Vasculitis-like
Metastasis vs. Primary Clinical Features (Met) Sudden appearance Multiple lesions Previous history Selected anatomic locations (umbilicus) (Primary) Previous, long-standing lesion
Primary Cutaneous Eccrine Carcinoma Metastatic Breast Adenocarcinoma
Primary Cutaneous Eccrine Carcinoma Metastatic Breast Adenocarcinoma p63
Primary Adnexal eccrine carcinoma CK5/6 CK7 Ducts Necrosis Calretinin
Marked atypia CK7 TTF1
p63 CK20
Practical Use of IPOX 1) Confirm diagnosis: - Keratin - CEA (EMA) 2) Primary vs metastatic: - P63 (>25% cells) - D2-40 - Calretinin - CK5/6 - CK7 3) Origin: - Mammaglobin - CK20 - CDX2, villin - CD19.9 - TTF1 - CD10 (EMA) - PSA / PSAP 4) Common sense and CPC!
Primary vs. Metastatic Summary Important differential diagnosis Clinical and histologic features IHC as an adjunct Most important tool: Telephone
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