ࡱ> 5@ ~bjbj22 -XX#L,mdxxxxxxxx    =E %%F%l$DoRq)lq xx )lxxm xx   xl PQٔ!Z m0mVrHjVrVr xvl$xxx)l)l  LOYOLA UNIVERSITY MEDICAL CENTER IRAP APRIL 23, 2012 Case 1: EBV Positive Large B-cell Lymphoma of the Elderly Lu Wang MD, Girish Venkataraman MD, Swati Mehrotra, MD Clinical History: An 81-year-old female noticed an enlarging nodule in the left parotid region for the past few months. She was otherwise asymptomatic. Her past medical history was significant for left breast cancer s/p lumpectomy and axillary lymph node dissection in 2004. At Loyola, physical examination showed a 6-cm tender, left parotid mass encompassing the entire parotid. After an initial fine needle aspiration, she underwent total parotidectomy. Diagnosis: EBV positive large B-cell lymphoma of the elderly (WHO 2008) Differential Diagnosis: Classical Hodgkin Lymphoma (cHL) T-cell/Histiocyte-Rich Large B-Cell Lymphoma (T/HRLBCL) Anaplastic Large Cell Lymphoma (ALCL) Angioimmunoblastic T-Cell Lymphoma (AITL) EBV Positive Large B-Cell Lymphoma of the Elderly Lymphomatoid Granulomatosis (LyG) Key Microscopic Features: Extranodal location with effaced architecture. May have large area of geographical necrosis Atypical B-cells with a spectrum in cell size, including many large transformed cells/immunoblasts and HRS-like giant cells Tumor cells expressing variably strong CD20, CD30 and EBV-LMP, and negative for CD15 Tumor cells are not angiocentric Discussion: Need to recognize this disease entity as a close mimic of cHL Remember to do EBER in cases with: Extranodal location DLBCL in older patients (>50yrs of age) Any polymorphous atypical (nodal/extranodal) lymphoid infiltrate Pattern of EBER positivity (small vs large vs both) is critical in making the distinction with cHL. References: 1. Dojcinov SD, Venkataraman G. Jaffe ES et al. Blood 2011 May 5;117(18):4726-35. 2. Shimoyama, Y. Pathology International 2009; 59: 835843 3. Shimoyama, Y. Cancer Sci. 2008; 99 (6): 1085-91 4. Swerdlow, SH, et al WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008) ISBN 978-92-832-2431 Case 2: Cellular Schwannoma Ugur Ozerdem, M.D., PGY-3, John M. Lee, M.D., Ph.D. Clinical History: 41 year-old woman presented in July 2010 with back and left shoulder pain. She had occasional numbness in her left chest, back and arm and had weakness in her left lower extremity as well. MRI showed a 3.8 cm left C7-T1 intradural extramedullary neoplasm extending from neural foramen into the spinal canal. Subsequently, she had a C7-T2 laminectomy with partial left T1/2 resection of the tumor. Fourteen months after the initial resection, her symptoms recurred; including left upper extremity numbness and decreased sensation in the left trunk, and the 4th and 5th digits of the left hand. A follow-up MRI of cervical/thoracic spine showed an increase in size of the residual tumor to 4.8 cm. Tumor has been re-resected with left thoracic T1-T2 extracavitary approach. A representative slide has been submitted for your review. Diagnosis: Cellular Schwannoma Differential Diagnosis Meningioma Smooth muscle tumors Schwannoma MPNST Melanoma Key Microscopic Features: Densely cellular, vaguely fascicular arrangement of cells with obscure cell borders consisting mainly of Antoni A pattern Low mitotic index Low Ki-67 proliferation index Focal arrangement of cells with whorls Focal areas of cells with cytoplasmic clearing Areas of pigmentation due to hemosiderin Focal areas of hyalinization of large vessels Resistance of specimen to disaggregation during smearing Discussion: Most schwannomas do not recur. However, cellular schwannomas, a subtype consisting of densely cellular Antoni A pattern may recur at rates as high as 50%. Mitosis index and Ki-67 indices do not reliably predict the recurrence. These tumors, despite high local recurrence rates, are not malignant and therefore they should not be overcalled as MPNST. About half of these cases are diagnosed as schwannomas initially and later diagnosed as cellular schwannomas after recurrence. References: 1. Cellular Schwannoma: A Clinicopathologic, DNA Flow and Proliferation Marker Study of 70 Patients. Casadei GP, Scheithauer BW, Hirose T, Manfrini M, Van Houton C, Wood MB. Cancer. 1995 Mar 1;75(5):1109-19. 2. Pathology of peripheral nerve sheath tumors: diagnostic overview and update on selected diagnostic problems. Rodriguez FJ, Folpe AL, Giannini C, Perry A. Acta Neuropathol. 2012 Mar;123 (3):295-319. 3. Cellular schwannoma. A clinicopathologic study of 57 patients and 58 tumors. White W, Shiu MH, Rosenblum MK, Erlandson RA, Woodruff JM. Cancer. 1990 Sep 15;66(6):1266 Case 3: Small Cell Carcinoma of the Hypercalcemic Type of the Ovary. Zulfiya Ibragimova MD., Jodi Speiser. M.D., aatay Erahin, M.D., PhD Clinical history: 27 year-old female presented with abdominal pain and increasing abdominal girth. Paracentesis at that time showed 350 cc of blood tinged fluid. CA-125: 307 U/ml (normal = <35 U/ml), preoperative blood Ca level was within normal limits. Diagnosis: Small cell carcinoma of the ovary, hypercalcemic type Differential diagnosis: Dysgerminoma Granulosa cell tumor, juvenile type Small cell carcinoma of the ovary, hypercalcemic type (O-SCCHT) Primary small cell carcinoma of the ovary, pulmonary type Metastatic small cell carcinoma of the lung Lymphoma Other  small round blue cell tumors (rhabdomyosarcoma, DSRBCT, etc.) Melanoma Key Clinical and Morphologic Features: Majority of neoplasms are composed of small cells 50% have large cell component (large cell varient) More than half of the large cell cases contain hyaline globules, giving a rhabdoid appearance Most display follicle-like spaces that are few in number, have variable shapes and contain eosinophilic secretions Nests, cords, clusters of cells and spindled cells, or mixture of patterns may be seen Rarely mucinous differentiation and well-developed mucinous cells resembling endocervical cells lining small cysts or signet ring cells may be seen Can have scant myxoid stroma, usually associated with large cell variant Immunohistochemistry -Positive: WT-1, CD10, calretinin and p53 -Negative: Inhibin, CD99, Chromogranin, Desmin and TTF-1 Discussion: Rare but highly malignant neoplasm Affects adolescents and young adults (9-43 years of age, ave 24 years) Non-specific symptoms: abdominal pain and/or swelling Highly aggressive tumors with dismal prognosis (<10% survival despite aggressive treatment) Prognosis most closely related to tumor stage 2/3 of the patients have associated paraneoplastic hypercalcemia Good prognostic factors: o -Age >30 years o -Size <10 cm o -No preoperative hypercalcemia o -Absence of large cells Refernces: 1. Powell JL et al. Uterine and ovarian conservation in advanced small cell carcinoma. Obstetrics and Gynecology 1998; 91 (5, Pt. 2): 846-848. 2. Rana S et al. Stage IIIC small cell carcinoma of the ovary: survival with conservative surgery and chemotherapy. Obstetrics and Gynecology 2004; 103 (5, Pt. 2): 1120-1123. 3. Tewari K et al. Advanced-stage small cell carcinoma of the ovary in pregnancy: long-term survival after surgical debulking and multi-agent chemotherapy. Gynecol Oncol 1995; 66: 531-534. 4. Reed WC et al. Small cell carcinoma of the ovary with hypercalcemia: report of a case of survival without recurrence 5 years after surgery and chemotherapy. Gynecol Oncol 1995; 56: 452-455. 5. Young RH et al. Small cell carcinoma of the ovary, hypercalcemic type: a clinicopathological analysis of 150 cases. Am J Surg Pathol 1994; 18: 1102-1116. Case 4: Diffuse Malignant Mesothelioma, Epithelioid Type Pranav Gandhi, MD; Umesh Kapur, MD Clinical History: The patient is an 81 year old male with a past medical history of dementia and recent long hospitalizations for small bowel obstruction who presents with severe, diffuse abdominal pain and non-bloody, non-bilious emesis. The radiological differential diagnosis on CT scan was an infectious or inflammatory process. Exploratory laparotomy revealed purulent fluid within the pelvis. The sigmoid colon was covered with fibrinous exudates and adherent to the lateral side wall. The clinical assessment was perforated diverticulitis with intra-abdominal abscess formation. A sigmoid colectomy with colostomy was performed Diagnosis: Diffuse, malignant mesothelioma, epithelioid type Differential Diagnosis: Mesothelial Hyperplasia Metastatic adenocarcinoma Epithelioid angiosarcoma Well-differentiated papillary mesothelioma Diffuse malignant mesothelioma, epithelioid type Keys to diagnosis: Dense, cellular proliferation appearing to originate from the serosal surface consisting of polygonal epithelioid cells with abundant eosinophilic cytoplasm and prominent nucleoli forming tubulo-papillary structures. Minor areas of the proliferation consisted of sheets of epithelioid cells with a greater degree of cytological atypia and pleomorphism. Positive immunohistochemical (IHC) staining for calretinin, CK7, and pankeratin, and negative IHC staining for MOC-31, Ber-Ep4, WT-1, CK 5/6 confirming mesothelial origin of the proliferation and eliminating metastatic adenocarcinoma and epithelioid angiosarcoma from the differential Deep stromal invasion of peri-colonic adipose tissue and muscularis propria eliminating reactive mesothelial hyperplasia and well-differentiated papillary mesothelioma from the differential Discussion: Our case represents one of the few cases reported in the literature of an unsuspected mesothelioma presenting as an acute inflammatory lesion without gross evidence of tumor Kerrigan et. al (2003) report a series of four cases of unsuspected mesothelioma presenting as acute appendicitis, acute cholecystitis and incarcerated umbilical hernia As the diagnosis is microscopic, the separation of reactive mesothelial hyperplasia and malignant mesothelioma is critical Reactive, cytologically atypical mesothelial cells may become entrapped in areas of active inflammation, mimicking invasion. The combination of proliferating mesothelial cells and fibrin is a sign of entrapment, regardless of how deep the proliferation is found. Inflammatory mesothelial proliferations may produce linear arrays of mesothelial cells formed from the apposition of two serosal surfaces in the midst of an inflammatory focus. The arrays may form complicated papillary excrescences and pinched off glands with individually atypical cells; however, this growth pattern is NOT a feature of malignant mesothelioma. Recent studies show that immunohistochemical staining for GLUT-1 was negative in all cases of reactive mesothelium, and positive in 89% of mesothelioma; thus, a positive result may be useful. References: 1. Kerrigan SA, Cagle P, Churg A. Malignant mesothelioma of the peritoneum presenting as an inflammatory lesion: a report of four cases.Am J Surg Pathol.2003;27(2):248253 2. AFIP Atlas of Tumor Pathology, Series IV: Tumors of the Serosal Membranes: District of Colombia, American Registry of Pathology, MD, MD, MD, 147 pp, Edited by Andrew Churg, MD, Philip T. Cagle, MD, Victor L. Roggli, MD. 2006, Washington. 3. Churg A, Colby TV, Cagle P, et. Al. The separation of benign and malignant mesothelial proliferations. Am J Surg Pathol 2000; 24: 1183-1200 4. Husain AN, et. al. Guidelines for Pathologic Diagnosis of Malignant Mesothelioma: A Consensus Statement from the International Mesothelioma Interest Group. Archives of Pathology & Laboratory Medicine: August 2009, Vol. 133, No. 8, pp. 1317-1331. 5. Baker PM, et. al. Malignant peritoneal mesothelioma in women: a study of 75 cases with emphasis on their morphologic spectrum and differential diagnosis. Am J Clin Pathol. 2005; 123: 724-737 6. Sugarbaker PH, et. al. A review of peritoneal mesothelioma at the Washington cancer Institute. Surg Oncol Clin North Am. 2003; 12: 605-621, xi. 7. Ordonez NG. What are the current best immunohistochemical markers for the diagnosis of epithelioid mesothelioma? A review and update. Hum Pathol. 2007;38:116. Case 5: Gastric Carcinosarcoma Zhihong Hu, MD, PhD; Sherri Yong, MD; Umesh Kapur, MD Clinical history: A 73-year-old male presented with a 3 month history of loss of appetite, fatigue, and loss weight of 30 pounds. Colonoscopy revealed diverticulosis, and EGD revealed gastric mass that was biopsied. The patient underwent subtotal gastrectomy which contained a white/tan fungating, polypoid, necrotic lesion with areas of hemorrhage and a variegated cut surface. Grossly, the mass appeared to invade into the muscularis propria. Diagnosis: Gastric Carcinosarcoma (Sarcomatoid Carcinoma) Differential diagnosis: Gastrointestinal stromal tumor (GIST) with adenocarcinoma (collision tumor) or GIST with entrapped glands Synovial sarcoma Gastroblastoma Sarcomatoid carcinoma Key microscopic features: The tumor composed of biphasic components. 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