Case 18. M75. Excision of mass on scalp. Clinically SCC. The best diagnosis is:

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1 Case 18 M75. Excision of mass on scalp. Clinically SCC. The best diagnosis is: A. Pilomatrical carcinoma B. Adnexal carcinoma NOS C. Metastatic squamous cell carcinoma D.Primary squamous cell carcinoma

2 Case 18 M75. Excision of mass on scalp. Clinically SCC.

3 Case 18 M75. NOTE: UNUSUAL PATTERN OF IN SITU CARCINOMA Excision of mass on scalp. Clinically SCC. The best diagnosis is:

4 PC2a. Male 85, mass on scalp. CK5, p63 positive. Answer C. metastatic squamous cell carcinoma (of lung)

5 Primary sites of origin of skin metastases: Breast carcinoma (female) > lung carcinoma > colorectal carcinoma > metastatic mucosal SCC from head and neck Less common gastric carcinoma, renal cell carcinoma, ovarian carcinoma, oesophageal carcinoma, other carcinomas and sarcomas Children neuroblastoma, rhabdomyosarcoma

6 Clues to a metastasis - Clinical: Site: scalp is the commonest site for cutaneous metastases other than breast carcinoma (anterior chest) neck (primary head and neck carcinomas especially SCC) and face. Trunk less common. often close to the internal primary malignancy (& locoregional skin in melanoma) e.g. Carcinomas of intra-abdominal origin metastasise often to the anterior abdominal wall & umbilicus (Sister Mary Joseph s nodule), ovarian carcinoma - perineum.

7 National Specialist Dermatopathology EQA Scheme 2017 case U337 Female 88 years. Skin ellipse excision, scalp. Skin tumour scalp. No other history available.

8 National Specialist Dermatopathology EQA Scheme 2017 case U337 Female 88 years. Skin ellipse excision, scalp. Skin tumour scalp. No other history available. Diagnosis: metastatic carcinoma

9 National Specialist Dermatopathology EQA Scheme 2017 case U337 Female 88 years. Skin ellipse excision, scalp. Skin tumour scalp. No other history available. NSD EQA Case U337 Case 18

10 National Specialist Dermatopathology EQA Scheme 2017 case U337 Diagnostic categories: Popularity: Score : 1 Metastatic carcinoma 2.55 REMOVED 2 Porocarcinoma 2.22 FROM 3 Neuroendocrine carcinoma / metastasis 2.20 SCORING 4 Basal cell carcinoma (+/- basosquamous) Sweat gland carcinoma/cutaneous adenoca Squamous cell carcinoma (+/- basaloid) Other diagnosis Poorly differentiated carcinoma 0.66 Other diagnoses : Sebaceous carcinoma (x4), trichilemmal carcinoma (x2), trichoblastic carcinoma, pilomatrical carcinoma (x3), No response, synovial sarcoma, melanoma. Inapproritae case (multiple). Original report : Metastatic carcinoma. (Subsequently found to have large cell neuroendocrine carcinoma of lung.)

11 Clues to a metastasis - Clinical: Age: Elderly patients (not a very helpful clue!) Sex: Female metastatic breast carcinoma accounts for 69% of cutaneous metastases in females

12 Clues to a metastasis - Clinical: Clinical history: Always check if unusual clinical findings or unusual histological features check for history of previous malignancy Clinical presentation: cluster of nodules, but often solitary nodule often rapidly growing and large Breast sclerotic areas on anterior chest wall, erythema

13 Presentation of metastasis many mimics: cyst pyogenic granuloma, hemangioma papular eruptions herpes zoster eruption, Rapidly infiltrating plaques, alopecic patches Cellulitis, erysipelas Hussein MR. Skin metastasis: a pathologist's perspective. J Cutan Pathol Sep;37(9):e1-20

14 Clues to a metastasis - Histopathology: Well-circumscribed nodule Presence of necrosis or haemorrhage dirty necrosis in colorectal carcinoma Lack of connection to the epidermis Lack of in situ component Unusual pattern of in situ component

15 Primary squamous cell carcinoma attached to epidermis

16 No connection to epidermis: metastatic SCC

17 No connection to epidermis: metastatic SCC Primary SCC of larynx

18 Male 82 solitary nodule right post-auricular region no connection to epidermis metastatic SCC from previous primary SCC skin of neck

19 Clues to a metastasis - Histopathology: Multifocality Vascular invasion

20 Unusual pattern of in situ carcinoma think epidermotropic metastasis rather than primary in situ carcinoma

21 Unusual pattern of in situ carcinoma focal

22 Solitary circumscribed nodules can be primary or metastatic carcinoma or primary benign adnexal neoplasm

23 Solitary circumscribed nodules always have metastasis in differential diagnosis

24 Male 57 solitary circumscribed nodule on trunk

25 Pitfall! Nodular hidradenoma common but has variable morphology: Mucinous metaplasia not adenocarcinoma

26 Growth pattern and glandular/ductal morphology not typical for primary carcinoma? think metastasis!

27 Metastatic adenocarcinoma of pancreas positive for CK7, CK20, CA19-9 negative for WT1, CDX2, p53

28 Immunohistochemistry for suspected metastasis or to exclude metastasis: If any of the clinical or histological features are unusual for a primary then consider immunohistochemistry for metastasis need to choose an immunohistochemical panel based on the histopathology and the clinical features. dependent on immunophenotype of specific primary or metastatic tumour Consider panel to include most common cancers: pancytokeratin, CK7, CK20 TTF-1, GATA3 (breast, urothelial), oestrogen receptor, PAX8 (females) PSA (males)

29 Case 18: Differential diagnosis: pilomatrical carcinoma Areas reminiscent of pilomatricoma but frankly carcinomatous (rare)

30 Case 18: Differential diagnosis: adnexal carcinoma NOS Primary skin adnexal neoplasms: usually p63 and podoplanin (D2-40) positive follicular lesions are usually also CK15 positive and ductal lesions are normally also basal cytokeratin (CK5, CK14, and CK17) positive unlike most metastases. therefore p63, D2-40, CK15 and CK5 may be helpful in select cases Positivity for all 3 of p63, D2-40, CK15 = good evidence for primary skin adnexal carcinoma but not definite evidence for a primary origin correlate with morphology and clinical features.

31 p63, podoplanin and cytokeratin 15 positive in most primary skin adnexal neoplasms and negative in metastatic adenocarcinoma Liang H, Wu H, Giorgadze TA, Sariya D, Bellucci KS, Veerappan R, Liegl B, Acs G, Elenitsas R, Shukla S, Youngberg GA, Coogan PS, Pasha T, Zhang PJ, Xu X. Podoplanin is a highly sensitive and specific marker to distinguish primary skin adnexal carcinomas from adenocarcinomas metastatic to skin. Am J Surg Pathol Feb;31(2): Plaza JA, Ortega PF, Stockman DL, Suster S. Value of p63 and podoplanin (D2-40) immunoreactivity in the distinction between primary cutaneous tumors and adenocarcinomas metastatic to the skin: a clinicopathologic and immunohistochemical study of 79 cases. J Cutan Pathol Apr;37(4): Mahalingam M, Nguyen LP, Richards JE, Muzikansky A, Hoang MP. The diagnostic utility of immunohistochemistry in distinguishing primary skin adnexal carcinomas from metastatic adenocarcinoma to skin: an immunohistochemical reappraisal using cytokeratin 15, nestin, p63, D2-40, and calretinin. Mod Pathol May;23(5):713-9.

32 Primary skin carcinoma follicular/trichilemmal

33 Primary skin carcinoma follicular/trichilemmal D2-40 (podoplanin) p63

34 Male 62. Skin nodule on neck

35 P63 negative podoplanin (D2-40) negative

36 Growth pattern and glandular/ductal morphology not typical for primary carcinoma? so Check for previous history of cancer Report your concern The diagnosis is uncertain; could be a primary or secondary epithelial neoplasm in the skin suggest full examination of patient may require radiological investigation eg CT scan