Case n 6 INSERM U970, Paris centre de Recherche Cardiovasculaire - - PowerPoint PPT Presentation

Case n°6

Pr Cécile Badoual Hôpital Européen Georges Pompidou, Paris INSERM U970, Paris centre de Recherche Cardiovasculaire (PARCC) Equipe 10, Immunologie et thérapie anti-angiogénique en

• ncologie

Clinical presentation :

• Tunisian 58 years old male
• ENT department for a mass on his left naris extending to superior lip.
• History of a sarcoma of his left leg treated in 2009 and 2012 surgery and

radiotherapy.

• Lung metastasis in 2011 treated by surgery.
• In 2018 the PET scan showed hypermetabolic masses in the lung, the

liver and the left naris.

• Biopsies of the naris mass.

Histopathology:

• Both lesions (naris and lip) : same histology.
• Proliferation of large cells with pleomorphic, rhabdoid or spindle

features.

• Cell borders are not well delineated.
• Nuclei are clear, with visible nucleoli.
• No clear differentiation (glandular, squamous..).
• Frequent atypias and mitosis.
• Focal necrosis.
• Perineural infiltrations, but no lymphovascular invasion.

Anti AE1/AE3

Chromogranin NCAM/CD56 Synaptophysin

Anti NUT

Anti INI1 (SMARCB1)

Anti KI67

Im Immunophenotyping : :

• AE1/AE3 positive
• p40, p63, CK5/6, CK7, CK20 negative
• P16 positive
• NUT negative
• Chromogranin, synaptophysin, NCAM negative
• 60 % of the tumor cells lost nuclear expression of INI1 (SMARCB1).
• Proliferation index (Ki67) is around 50-70 %.

INI1-deficient p16+ carcinoma

Anti-CD34 staining has been performed, due to the sarcomas anteriority’s. Tumor cells showed a strong expression of CD34.

Epithelioid sarcoma (lip and naris metastasis)

Epit ithelioid sarcoma

• Rare
• Approximately 4% of the ESs occur in head and neck.
• Men > women
• Adolescents > adults.
• Flexor surfaces of fingers and hand > wrist and forearm > knee and lower

leg > buttocks, thigh > shoulder, arm, ankle, foot and toes.

• The origin of the cells is still not known

Epithelioid sarcoma

• Nodular growth with central necrosis and peripheral palisade
• Epithelioid and spindle cells
• Slight nuclear pleomorphism, round to oval vesicular and central nuclei,

eosinophilic cytoplasm, ill-defined cell borders

• Neurotropism and perivascular invasion
• High mitotic activity.
• Epithelial markers : EMA, AE1/AE3, CK8,CK19 +
• Vimentin +
• CD34 + in more than 50%
• ERG expression is inconstant, other endothelial markers are negative

Epit ithelioid sarcoma

• Loss of nuclear expression of INI1 (SMARCB1 protein) is invariant.
• SMARCB1 is a tumor suppressor gene located 22q11.2
• Expression is lost in distal and proximal types of Ess
• Aberrant expression of SMARCB1/INI1 : malignant rhabdoid tumor

(atypical teratoid/rhabdoid tumor), epithelioid sarcoma, renal medullary carcinoma, epithelioid malignant peripheral nerve sheath tumor, myoepithelial tumor, extraskeletal myxoid chondrosarcoma, pediatric chordoma, pancreas undifferentiated rhabdoid carcinoma, sinonasal basaloid carcinoma, rhabdoid carcinoma of the gastrointestinal tract.

Epithelioid sarcoma

• Complete surgery is necessary
• Multiple recurrence are frequent when resection are incomplete
• 5 year survival rates are : 50-85%
• 10 year survival rates are : 42-55%.
• Adverse prognostic feature include : male gender, advanced age at diagnosis,

large tumor size (>5cm), non distal extremity location, high mitotic rate, angioinvasion, hemorrhage and necrosis, inadequate initial excision, multiple recurrences, metastatic disease at presentation.

• Clinical history
• Subtype of indifferenciated carcinoma with basaloid and rhabdoid features
• Dispersed chromatin and indistinctive cytoplasmic borders.
• Mitotic rates high, and necrosis common.
• No squamous dysplasia/in situ carcinoma
• Presence of non-specific, clear, “empty” cytoplasmic vacuoles
• There is no expression of CD34

Dif ifferential dia iagnoses:

INI1-deficient sinonasal carcinoma

Agaimy, AmJ Surg Pathol 2017

Agaimy, AmJ Surg Pathol 2017

Loss of SMARCB1, SMARCB2 reduced, SMARCB4 and ARID1A intact

• New, rare but certainly under diagnosed entity
• Subset of highly aggressive poorly differentiated

carcinoma

• Very monotonous epithelial proliferation with abrupt

keratinization (or large clear cells)

• Any age but median age about 20 years old
• Rearrangement of the NUT (aka NUTM1, nuclear protein

in testis) gene, most commonly fused to BRD4.

• Anti-NUT immunochemistry
• Targeted therapy : Register patients in the database:

www.nmcregistry.org

Differential diagnoses:

Nut carcinoma

Anti AE1/AE3

Anti NUT

Dif ifferential dia iagnoses:

Monophasic epithelioid synovial sarcoma

• Rare in sinonasal tract and skull.
• Poorly differentiated tumours with frequent mitoses and necrosis.
• There is a quite constantly TLE1 nuclear immunoreactivity (95%).
• This sarcoma has variable positivity for CD99, BCL2, and CD56; and

patchy to focal reactivity with epithelial markers (EMA), cytokeratins (AE1/AE3, CK7), and BerEP4. The tumors are usually negative for S100 and CD34. There is no loss of expression of INI1.

• The chromosomal translocation t(X;18)(p11;q11) is a specific genetic

alteration in synovial sarcomas.

Take Home message

• Undifferenciated carcinoma think about NUT and INI1 immunostaining
• But pay attention to the clinical history

1- Wenig B, Atlas of Head and Neck Pathology, 3rd Edition, Elsevier Ed, p 523-524; 2016. 2-Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF. Epithelioid sarcoma: an immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol. 1999;30(8):934-42. 3- Kenichi K, Yoshinao O. Oncogenic roles of SMARCB1/INI1 and its deficient tumors. Cancer Sci. 2017 Apr; 108(4): 547–552 4- WHO Classification of Head and Neck Tumours, WHO Classification of Tumours, 4th Edition, Volume 9; Edited by El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. 2017 5- Srinivasan A, Tuluc M, Jordan AJ Jr, Curry JM, Bilyk JR. INI1/SMARCB1-Deficient Carcinoma (Rhabdoid Tumor) of the Lacrimal Gland. Ophthalmic Plast Reconstr Surg;35(2). 6 - Agaimy A, Koch M, Lell M, et al. SMARCB1(INI1)-deficient sinonasal basaloid carcinoma: a novel member of the expanding family of SMARCB1-deficient neoplasms. Am J Surg Pathol 2014;38:1274-81. 7- Agaimy A, Hartmann A, Antonescu CR, et al. SMARCB1 (INI-1)- a series of 39 cases expanding the morpho-logic and clinicopathologic spectrum of a recently described entity. Am J Surg Pathol 2017;41:458-71 8- Kakkar A, Antony VM, Pramanik R, Sakthivel P, Singh CA, Jain D. SMARCB1 (INI1) deficient sinonasal carcinoma: a series of 13 cases with assessment of histologic patterns. Hum Pathol. 2019 83:59-67. 9-Thompson L, Head and neck pathology, 2nd Edition - Diagnostic pathology series Saunders Ed; 2012

Take Home message

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