USCAP 2016 Evening Specialty Conference:
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1 USCAP 2016 Evening Specialty Conference: USCAP 2016, Seattle, Washington Moderator: Ilan Weinreb, MD
2 Head/Neck/Endo Pathology Specialty Conference Tuesday March 15th, 2016 from 7:30-9:30 PM Alena Skalova, MD, PhD Professor of Pathology Charles University, Faculty of Medicine in Plzen, Czech Republic
3 ACCME/Disclosures Dr. Alena Skálová declares she has no conflicts of interest to disclose.
4 Head/Neck/Endo Pathology Specialty Conference: presented by Alena Skalova Case 1
5 Short clinical history and gross appearance 60-year-old man presented with tumor of the palate, that has been slowly growing for about 5 years The tumor, measuring 5x4x4 cm, showed accelerated growth in recent few months with invasion of bone and infiltration of paranasal sinuses After a partial right maxillectomy, the patient was reoperated due to recurrent tumor 11 months after first surgery and recieved irradiation therapy.
6 Short clinical history and gross appearance Second recurrance appeared after 5 years with signs of infiltration of the right orbite within the next one year, the patient revealed multinodular third recurrent tumor infiltrating the orbite, nasal cavity, ethmoid sinus, pterygopalatinal fossa and right cheek patient declined the suggested radical maxillectomy despite radiation therapy he died with recurrent disease 8 years after primary surgery
7 Tumor of the palate, multilobulated growth pattern
8 tumor nodules reveal areas of pseudocystic degeneration
9 Central comedo-like necrosis
10 Lobulated growth, deposits of hyalinized extracellular matrix
11 Tumor lobules devided by thin fibrous septa
12 Abundant hyalinized extracellular deposits
13 Foci of myxoid stroma
14 Extensive hyalinized stroma, squamous metaplasia
15 Lobulated growth
16 Clear cytoplasm
17 Hyalinized and cellular fibrous septa
18 Solid growth pattern, prominent clear cell change
19 Immunophenotype Case 1
20 S100 protein
21 CK14
22 P63 protein
23 SOX10
24 MIB1
25 Molecular testing FISH analysis using EWSR1 dual-color, break apart Probe (Abbott Molecular) 29/100 nuclei positive for EWSR1 break Cut-off 10%
26 FISH EWSR1 positive (29/100)
27 Diagnosis Case 1: Clear Cell Myoepithelial Carcinoma with EWSR1 Rerrangement
28 Discussion Case 1
29 Myoepithelial carcinoma Myoepithelial carcinoma (MC) is a rare malignant tumor, comprising <2% of all salivary gland carcinomas Most cases arise in parotid gland MCs also occur in submandibular and minor glands, usually the palate, less common base of tongue, maxillary sinus and larynx may arise de novo, but at least half of them develop in pre-existing pleomorphic adenoma (PA) or benign myoepithelioma particularly in recurrences
30 Myoepithelial carcinoma: lobulated growth pattern, myxoid stroma, pseudocystic trnansformation, epithelioid cells
31 myxoid
32 Spindle-shaped myoepithelial cells
33 Epithelioid, clear cells
34
35 Clear Cell Myoepithelial Carcinoma Clear cell MC is composed of solid nodules separated by thin fibrous septa polyhedral cells with abundant clear cytoplasm and round, sometimes vesicular nuclei with well defined boundaries Comedo-like necrotic foci are often seen Patchy squamous metaplasia is often present presence of PAS positive hyaline deposits of basement membrane-like extracellular matrix material
36 CCMC with comedo-like necrosis
37 Pseudocystic change
38 Squamous metaplasia
39 Tumor necrosis
40
41 5 salivary gland myoepithelial carcinomas (ex-pa) 5 salivary gland mucoepidermoid carcinomas
42 Am J Surg Pathol 2015;39: EWSR1 rearrangement was detected 20 / 51 of CCMC de novo (39%) 5 / 21 cases of CCMC ex PA (24%) 1 /11 cases of epithelial-myoepithelial carcinoma (9%) 3 /4 cases of HCCC (75%)
43 Clinical follow-up of CCMC available in 21 patients (84%) 3 patients - alive with recurrent/metastatic disease 8 died of disseminated cancer 9 months to 16 years after diagnosis (mean 6 years) LN mets - 5 patients within 5 months to 4 years after diagnosis (mean 22 months) distant mets - 7 patients o orbit (2 cases), one case each neck soft tissues, liver, lungs, mediastinum, and thoracic vertebra
44 Differential diagnosis Case 1: Clear Cell Myoepithelial Carcinoma with EWSR1 Rerrangement
45 Differential diagnosis Hyalinizing clear cell carcinoma of minor salivary glands/clear cell odontogenic carcinoma clear cell variant of squamous cell carcinoma mucoepidermoid carcinoma clear cell calcifying epithelial odontogenic tumor epithelial-myoepithelial carcinoma Clear cell acinic cell carcinoma metastatic renal cell carcinoma oncocytoma, myoepithelioma etc.
46 Hyalinizing clear cell carcinoma of minor salivary glands p63 protein EWSR1-ATF1 fusion, immunoprofile: CK+/p63+/myoepi markers-
47 Clear cell odontogenic tumor p63 protein p63 positive, but other myoepithelial markers absent
48 Clear Cell Squamous Cell Carcinoma p63 protein p63 positive, but other myoepithelial markers absent EWSR1 intact
49 Mucoepidermoid carcinoma t(11;19) translocation -CRTC1-MAML2 fusion Mucin+/p63+/CK+/ S100 /myoepi markers- p63 protein
50 Epithelial-Myoepithelial Carcinoma
51 Prognostic Factors in Myoepithelial Carcinoma Myoepithelial carcinoma (MC) has a diverse clinical behavior Grading controversial one third of patients die of disease, another third have multiple recurrences, and the remaining third are disease free o Simpson RHW. Current Diagn Pathol 2002; 8, Marked cellular pleomorphism, high mitotic rate and high proliferative activity (MIB1 index) correlate with poor prognosis o Savera et al, Am J Surg Pathol 2000; 24: o Nagao et al, Cancer 1998; 83:
52 Prognostic Factors in Myoepithelial Carcinoma MC is a relatively aggressive tumor that is associated with a high rate of distant metastasis grading system based on the presence of tumor necrosis should be used to identify high-grade MC and predict its clinical behavior o Kong, et al. Am J Surg Pathol 2015;39: acquisition of EWSR1 rearrangement in CCMC may be the driver of the high-grade malignant phenotype and hence aggressive clinical behavior o Skalova, et al Am J Surg Pathol 2015;39:
53 Head/Neck/Endo Pathology Specialty Conference: Case 1 Thank you for your attention
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