3/28/2017. Head and Neck/Endocrine Pathology Specialty Conference Case 4 Raja R. Seethala, M.D. University of Pittsburgh Medical Center

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1 Head and Neck/Endocrine Pathology Specialty Conference Case 4 Raja R. Seethala, M.D. University of Pittsburgh Medical Center Disclosure of Relevant Financial Relationships Disclosure of Relevant Financial Relationships USCAP requires that all planners (Education Committee) in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. USCAP requires that all faculty in a position to influence or control the content of CME disclose any relevant financial relationship WITH COMMERCIAL INTERESTS which they or their spouse/partner have, or have had, within the past 12 months, which relates to the content of this educational activity and creates a conflict of interest. Dr. Raja R. Seethala declares he has no conflict(s) of interest to disclose. Clinical History: 41 year old female with a right parotid "lump" apparently present since childhood but with a recent increase in size over the past year. By clinical and radiologic examination, the lesion surrounded the facial nerve and involved the digastric and stylopharyngeus muscles. A right parotidectomy, soft tissue resection in the region of the styloid, and a selective level IIB neck dissection were performed. 1

2 Parotid 2

3 Styloid 3

4 Summary of Findings Parotid Bland but infiltrative keratinizing squamous proliferation with minor squamoglandular component Styloid - Bland but infiltrative squamoglandular proliferation with focal keratinization and mucus extravasation One or Two Lesions? Differential Diagnoses What is wrong with MEC here? Single Lesion? Branchial cleft anomaly Squamous cell carcinoma (SCC) involving a duct Adenosquamous carcinoma Keratinizing mucoepidermoid carcinoma (MEC) Keratocystoma MEC hybrid Keratocystoma with mucinous metaplasia Metaplastic Warthin tumor or pleomorphic adenoma Skin adnexal tumor -_- Collision? (two lesions) Branchial cleft cyst and SCC or MEC SCC + MEC Keratocystoma +MEC Classic MEC phenotype: Epidermoid cell Intermediate cell Mucous cell or columnar (mucin poor) glandular cell Adapted from Luna et al, 2006 Clear cell or oncocyte Squamous cell Overt keratinization is rare and focal Too much keratinization think adenosquamous carcinoma Whats wrong with adenosquamous carcinoma (AsqCA) here? SCC variant with glandular differentiation Prototypically high grade and keratinizing Key features Surface dysplasia Pronounced keratinization Infiltrative growth Discrete glandular foci Pronounced nuclear atypia Well differentiated variants exist but Pronounced keratinization and infiltration is all we have so far here Flashback: 2011 USCAP evening conference Case 3 in San Antonio: A well differentiated AsqCA Ciliated adenosquamous carcinoma often bland, largely nonkeratinizing and HPV driven Current case no ciliated components and tumor is heavily keratinizing p16 HPV DNA ish 4

5 What about Keratocystoma? Exceptionally rare, bland keratinizing multicystic proliferation M:F 5:2, mean age: 37 years (range: 8-49 years), all parotid No recurrences (mean f/u: 33 months, range months; n=6) No malignant transformation or glandular components to date Our case shows infiltration and PNI and glandular components Let s try 1 st Branchial cleft anomalies Typically 1 st to 2 nd decade of age (patient had a lesion since childhood ) can be a sinus, fistula or cyst Two types (Work 1972) Type I ectodermal reduplication of external auditory canal Type II ectodermal and mesodermal contains adnexae and cartilage Histologically bland and architecturally unilocular and recapitulates skin Let s try again. 1 st Branchiogenic carcinoma???? ~ 6 cases reported Usually derived from type II anomalies All reported cases were conventional SCC, no glandular elements Possible here? Theoretically In practice 5

6 Mythos of Branchiogenic Carcinoma Revisited Problems with Other Options Metaplastic Warthin tumor (WT) Metaplastic Pleomorphic adenoma (PA) Current case: infiltrative and no evidence for residual PA or WT Best to be skeptical given our stellar track record with 2 nd branchiogenic carcinomas (AKA misclassified cystic HPV related SCC metastases) Metaplastic PA Metaplastic WT Summary of Diagnostic Considerations. Bland but infiltrative squamoglandular lesion of parotid Does not fit cleanly into MEC or AsqCA Some problems with other considerations like keratocystoma, 1 st branchial cleft cyst (or carcinoma), and metaplastic WT and PA Still not clear whether this is one lesion (variant/hybrid tumor) or a collision of two of these previously mentioned entities Further Classification Concepts Collision Tumor/ tumor to tumor metastasis Hybrid Tumor Variant Morphology Two lesions coalescing at one site Single lesion Single lesion Presumed separate site or compartment for each Single site or compartment Single site or compartment Two distinct morphologies Two distinct morphologies Two morphologies, not always distinct, one usually dominates No true transition Transition can be noted Transition common Incorporation of Molecular Phenotype Collision Tumor/ tumor to tumor metastasis Hybrid Tumor Variant Morphology Two lesions coalescing at one site Single lesion Single lesion Presumed separate site or compartment for each Single site or compartment Single site or compartment Two distinct morphologies Two distinct morphologies Two morphologies, not always distinct, one usually dominates No true transition Transition can be noted Transition common Each component - distinct molecular alterations Shared & distinct molecular alterations Shared molecular alterations Immunohistochemistry 6

7 Other Immunostains CK 5/6 positive Cam positive P16 negative (as a surrogate marker of high risk HPV) HPV ISH - negative ER negative PR negative AR negative p63 P53 rare cells ( wild type ) Ki-67 low (~2-3%) CD34 focal stromal staining STYLOID MAML2-FISH MEC 1 Dual Color Break-apart Probe (ZytoVision, Bremerhaven, Germany) PAROTID Differential Diagnoses Differential Diagnoses Single Lesion? Collision? (two lesions) Single Lesion? Collision? (two lesions) Branchial cleft anomaly Squamous cell carcinoma (SCC) involving a duct Adenosquamous carcinoma Keratinizing mucoepidermoid carcinoma (MEC) Keratocystoma MEC hybrid Keratocystoma with mucinous metaplasia Metaplastic Warthin tumor or pleomorphic adenoma Skin adnexal tumor -_- Branchial cleft cyst and SCC or MEC SCC + MEC Keratocystoma +MEC Keratinizing mucoepidermoid carcinoma (MEC) Keratocystoma MEC hybrid SCC + MEC Branchial cleft cyst and SCC or MEC Keratocystoma +MEC 7

8 Differential Diagnoses Single Lesion? Keratinizing mucoepidermoid carcinoma (MEC) Keratocystoma MEC hybrid SCC + MEC The Name Game Keratocystoma MEC hybrid Somewhat reasonable, but keratinizing component is also malignant SCC-MEC hybrid Also reasonable (what I called it in 2011) but misleading since 1 SCC of salivary gland is virtually non-existent, and usually higher grade Final Diagnostic Interpretation (ver 2011) MEC with SCC component (i.e. hybrid), Intermediate Grade +PNI, Ø ALI 0/12 neck LN Keratinizing MEC Respects the common clonal origin and somewhat reconciles the bland morphology of both components Final Diagnostic Interpretation (ver 2017) Keratinizing MEC, Intermediate Grade +PNI, Ø ALI 0/12 neck LN Keratinizing MEC Is this a thing??? No similar molecularly confirmed cases to date. Most similar example MEC associated with sialadenoma papilliferum (i.e. papilliferum like change) F/U XRT 2011 Recurrence chemo NED as of 2/2017 8

9 Expanding the spectrum of MEC Unresolved Issues Common variants Clear cell Oncocytic Sclerosing Unusual/putative variants Sialadenoma Papilliferum like?mucoacinar Carcinoma?Keratinizing Mucoacinar carcinoma, Bundele et al, Poster #1294 SOX10 DOG1 MAML2 How to grade -?Cystic and bland, but infiltrative with PNI (mostly keratinizing component) Given discordant features intermediate grade assigned Etiology if accepted as a variant -?Infarcted/metaplastic MEC Does the childhood history of a mass mean anything or is it a red herring? Summary Rare case of translocation proven MEC with keratinizing (SCC like) component Both components are bland but infiltrative and locally aggressive Both components share common molecular phenotype arguing against a collision. Forces a reassessment of morphologic possibilities for MEC Reasons for keratinizination speculative Important Information Regarding CME/SAMs The Online CME/Evaluations/SAMs claim process will only be available on the USCAP website until September 30, No claims can be processed after that date! After September 30, 2017 you will NOT be able to obtain any CME or SAMs credits for attending this meeting. THANK YOU Special Thanks to Dr. Donald Rankin, Loma Linda University original case contributor who provided additional follow-up as well 9