SL-26 Pulmonary Pathology Slide Seminar Case 3 Lucian R. Chirieac, - PowerPoint PPT Presentation

SL-26 Pulmonary Pathology Slide Seminar Case 3 Lucian R. Chirieac, M.D. Department of Pathology Brigham and Women’s Hospital Harvard Medical School Boston, MA HARVARD BRIGHAM AND MEDICAL SCHOOL WOMEN’S HOSPITAL

Case 3 42-year-old male who presented with flu-like symptoms and shortness of breath. Imaging reveals pericardial effusion. Evacuation and pericardial cytology was benign (abundant neutrophils and occasional reactive mesothelial cells). Pleural fluid, cytopathology report was negative for malignant cells.

Case 3 Cardiac MRI - circumferential 8 mm thickening of pericardium, with reduced left ventricular ejection fraction. Surgery - anterior pericardium, pericardiectomy. A full dissection of the pericardium from the left ventricle was attempted but not feasible. Chest and abdomen CT scan • Pericardial thickening and pericardial effusion, right pleural effusion with subcentimeter noncalcified nodules. • Passive hepatic congestion, likely reflecting constrictive pericarditis.

Case 3 Medical History • Hodgkin's disease, nodular sclerosing - Diagnosed in 1987 - Treated with external beam radiation and splenectomy • Hepatitis • Hypothyroidism

H&E 400x

H&E 400x

H&E 200x

H&E 400x

H&E 400x

H&E 1000x

Differential Diagnosis • Metastatic Carcinoma: should be further investigated by immunohistochemistry, CT exam and/or biopsies if clinically indicated. • Angiosarcoma: epithelioid histology • Malignant Solitary Fibrous Tumor • Malignant Mesothelioma • Germ Cell Tumor

AE1/AE3 200x

Calretinin 200x

Calretinin 600x

WT-1 100x

D2-40 200x

Immunoperoxidase Studies ANTIBODY RESULT COMMENT Cytokeratin + Positive CK 7 + Positive + Membranous, positive D2‐40 Calretinin + Positive + Positive, nuclear WT‐1 ‐ Absence of cytoplasmic staining CK 20 TTF‐1 ‐ Absence of nuclear staining ‐ Absence of staining CEA S100 ‐ Absence of staining ‐ Absence of staining Melan–A ‐ Absence of staining HMB‐45 p63 ‐ Absence of staining ‐ Absence of staining CDX2

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Pathologic Classification of Diffuse Malignant Mesothelioma Epithelioid mesothelioma Sarcomatoid mesothelioma (spindle cell) Desmoplastic mesothelioma (variant of sarcomatoid mesothelioma) Biphasic mesothelioma

Epithelioid MM Sarcomatoid MM Biphasic MM Biphasic MM

Overall Survival (%)

Histologic Subtypes and Patterns of Malignant Mesothelioma Epithelioid Mesothelioma Sarcomatoid Mesothelioma Tubulopapillary Conventional, spindle cell Micropapillary Desmoplastic Trabecular Heterologous differentiation (osteosarcomatous, Acinar chondrosarcomatous, etc.) Adenomatoid Lymphohistiocytoid (may also be Solid classified as epithelioid) Clear cell Deciduoid Biphasic/Mixed Adenoid cystic Signet ring cell Small cell Rhabdoid Pleomorphic 2018 U pdate o n the Guide line s by the I MiG Re c o mme ndatio ns

Histologic Subtypes and Patterns of Malignant Mesothelioma Epithelioid Mesothelioma Sarcomatoid Mesothelioma Tubulopapillary Conventional, spindle cell Micropapillary Desmoplastic Trabecular Heterologous differentiation (osteosarcomatous, Acinar chondrosarcomatous, etc.) Adenomatoid Lymphohistiocytoid (may also be Solid classified as epithelioid) Clear cell Deciduoid Biphasic/Mixed Adenoid cystic Signet ring cell Small cell Rhabdoid Pleomorphic 2018 U pdate o n the Guide line s by the I MiG Re c o mme ndatio ns

Malignant Mesothelioma Pleomorphic Histology

Overall survival by histologic type in 2582 patients with diffuse malignant pleural mesothelioma Adapted from MESOPATH reference center 1998 et 2010 . Courtesy Dr. Francoise Gallateau‐Salle

Unusual Subtype of Mesothelioma Diffuse Malignant Mesothelioma, Epithelioid type - Pleomorphic subtype - Involving the pericardium - Secondary to therapeutic radiation

Malignant Mesotheliomas Arising in Patients with a History of Radiation Chirieac et al. J Clin Oncol. 2013 Dec 20;31(36):4544‐9 Unpublished Data

Malignant Mesotheliomas Arising in Patients with a History of Radiation Cumulative frequency (Kaplan Meier estimate) of Malignant Mesothelioma in patients who received therapeutic radiation. The median latency interval is 19.25 years in 90 patients with pleural, peritoneal and pericardial mesotheliomas secondary to therapeutic radiation reported in the literature.

Malignant Mesotheliomas Arising in Patients with a History of Radiation Chirieac et al. J Clin Oncol. 2013 Dec 20;31(36):4544‐9

Table 1. Clinical and Pathologic Characteristics of Patients with Lymphoma-associated PDMM and Asbestos-associated PDMM. Lymphoma- Asbestos- associated PDMM associated PDMM Characteristic (N=22) (N=1596) P Value * Sex – no. (%) 0.82 Female 5(22.7) 331 (20.7) Male 17 (77.93) 1265 (79.3) Age – (years) <0.0001 Mean 46.7 63.3 Median (range) 45 (27-79) 64 (17-93) Asbestos bodies* (count/g) 0.0007 Mean 21 5850 Median (range) 15 (0-56) 325 (0-1.4x10 6 ) Histology – no. (%) 0.21 Epithelioid 17 (77.3) 973 (60.9) Biphasic 5(22.7) 502 (31.5) Sarcomatoid 0(0) 121 (7.6) Primary location† – no. (%) 0.44 Left Pleura 12 (54.5) 646 (41.0) Right Pleura 10 (45.5) 927 (58.9) Surgery‡ – no. (%) 0.71 Complete macroscopic cytoreduction 13 (76.5) 884 (80.1) Incomplete resection 4(23.5) 219 (19.9) Chirieac et al. J Clin Oncol. 2013 Dec 20;31(36):4544‐9

Overall Survival of Patients with Malignant Mesotheliomas Arising in Patients with a History of Radiation 100 80 Overall Survival (%) 60 Lymphoma- associated 40 PDMM Asbestos- 20 associated PDMM P =0.02 0 0 36 72 108 144 180 Time (months) Chirieac et al. J Clin Oncol. 2013 Dec 20;31(36):4544‐9

Summary • Diffuse malignant mesothelioma, epithelioid type, pleomorphic subtype is a distinct entity of special interest which has a poor prognosis similar to sarcomatoid mesothelioma. • Patients with malignant mesothelioma secondary to therapeutic radiation have unique features: • Unique, rare histologic subtypes, including pleomorphic. • Young age ( aprox 40 years) • Arise in patients with a history of therapeutic radiation 20 years later. • Pericardial mesotheliomas are exceedingly rare.

Follow Up • 1 month - Started the first cycle of chemotherapy with pemetrexed and cisplatin • His course has been complicated by acute renal failure. • 12 months - CT abdomen and pelvis • Intraperitoneal fluid • Multiple soft tissue mesenteric nodules suggestive of progression of patient's known malignant mesothelioma. • Enlarging bilateral pleural effusions.