—  SPECIALTY CONFERENCE HANDOUT  — Hematopathology Thursday, March 3, 2011, 7:30 PM CC 103 A/B Clinical histories are printed below. Click on the case numbers for text and references of each case. Click on each slide thumbnail image for an enlarged view A Provocative Potpourri of Potentially Problematic and Perplexing Proliferations Moderator: ADAM BAGG University of Pennsylvania Philadelphia, PA Disclosure: In accordance with ACCME guidelines regarding disclosure, the USCAP policy requires that faculty members who have a significant financial or other relationship with a commercial company, entity, or service (which will be discussed in this Symposium) must disclose this to attendees. The Academy also requires that speakers disclose any products that are not labeled for the use under discussion. The speakers listed below have indicated they have nothing to disclose. Panelists: Megan Lim, University of Michigan, Ann Arbor, MI Scott Rodig, Brigham and Women’s Hospital, Boston, MA Laurence de Leval, University of Lausanne, Lausanne, Switzerland Stefano Pileri, Bologna University, Bologna Italy Clinical Histories and Still Images are displayed below. Click on slide thumbnail images for an enlarged view. If you have any difficulties viewing these slides, email or call George Clay at +1.724.449.1137. Case 1 - Click here for Text and References Submitted by: Megan S. Lim - Clinical Summary: A 29-year-old woman presented with a two month history of early satiety, abdominal discomfort, constipation, and progressive fatigue. She underwent gastrointestinal endoscopy and was found to have grade I varices on upper endoscopy with an unremarkable colonoscopy. Computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen demonstrated peri-pancreatic edema with a possible pancreatic head mass, and portal vein thrombus. An exploratory laparotomy revealed no definitive mass and the biopsy demonstrated fibroadipose tissue with inflammation and fat necrosis. She was discharged from the hospital after experiencing minimal improvement. Over the ensuing six month period she continued to experience unexplained abdominal pain and progressive jaundice. During her final presentation, she suffered from failure to thrive, worsening abdominal pain, and lower extremity claudication. She failed to respond to steroid therapy. She acutely decompensated, developing bacteremia and multi-system organ failure. The patient expired and an autopsy was performed. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Figure 1 Clusters of neoplastic cells are embedded in areas of dense fibrosis. Case 1 - Figure 2 The neoplastic cells exhibit perivascular growth pattern within the liver. The cells are pleomorphic with wreath-like nuclei and prominent nucleoli. Case 1 - Figure 3 Neoplastic cells are CD20 negative. Case 1 - Figure 4 Neoplastic cells are CD3 negative. Case 1 - Figure 5 The tumors cells express CD30. Case 1 - Figure 6 The tumor cells express ALK-1 within the nucleus and cytoplasm. Case 2 - Click here for Text and References Submitted by: Scott J. Rodig - Clinical Summary: This is a biopsy from a 64 yo female with had a history of new, intermittent abdominal pain. A CT scan showed a large (8 X 7 cm) retroperitoneal mass on the pancreas. Patient has a history of fibroids only. Pertinent Laboratory Data: White count = 7.5, normal differential Hematocrit = 41 Platelets = 331 LDH = 364 (normal range 135-214) No palpable andenopathy Case 2 - Slide 1 Large lymphoid cells growing in a diffuse pattern with irregular nuclear contours, immature chromatin, prominent nucleoli. Click to view with ImageScope Click to view with a Web-Based Viewer Case 2 - Figure 1 Additional H&E stained section of the tumor. Case 2 - Figure 2 Immunostain for CD20. Case 2 - Figure 3 Immunostain for CD10. Case 2 - Figure 4 Immunostain for Bcl2. Case 2 - Figure 5 Immunostain for MIB1. Case 2 - Figure 6 FISH for cMYC with split-apart probe set. Case 2 - Figure 7 FISH for IgH and BCL2 using fusion probe set. Case 3 - Click here for Text and References Submitted by: Laurence L. de Leval - Clinical History: A man aged 57 with no previous medical history presented with generalized lymphadenopathy. The biopsy is from an inguinal lymph node, 1.5 cm. Case 3 - Slide 1 Click to view with a Web-Based Viewer Case 4 - Click here for Text and References Submitted by: Stefano A. Pileri - Clinical Summary: A 5 year-old Caucasian child referred to the Department of Paediatrics of Catholic University in Rome because of migrant joint pain and swelling of the right sub- mandibular gland and latero-cervical lymph nodes. Total body CT-scan resulted negative whereas bone scintigraphy showed an increased uptake in the right shoulder, right foot and ribs. A bone marrow (BM) aspirate and a biopsy of the right sub-mandibular gland turned out negative. The patient was discharged with a diagnosis of Parvovirus B19 infection based on a PCR positive test performed on BM, peripheral blood and saliva. Accordingly, a therapy with FANS and intravenous immunoglobulins was administered. For the onset of a deficit of the right detrusor muscle of the sub-mandibular angle, interpreted as iatrogenic, steroid therapy was then started. One month later, a nodule measuring 3 cm across and extending from the left nasal fossa to the homolateral hard palate was detected. Staging procedures were negative. An incisional biopsy was performed: the material was sent in consultation to the Unit of Haemolymphopathology of Bologna University. Following the diagnosis, the patient underwent chemotherapy according to the AIEOP LAM 2002/1 protocol achieving complete remission. Pertinent Laboratory Data: Immunomorphologic findings The biopsy consisted of fragments of palatine mucosa whose chorion was infiltrated by large blasts, with round or kidney-shaped nuclei, rather dispersed chromatin, prominent central nucleoli, an a wide rim of cytoplasm, grayish at Giemsa. The growth either dissociated the dermis producing a Indian file appearance or gave rise to cuffs around vessels. Mitotic figures were numerous. At immunohistochemistry, the above described population resulted: CD45+, CD68PGM1+, CD43+, BCL2+, Vimentin+, CD99+, CD56-/+, TdT-, CD34-, MPO-, PAX5-, CD3-, CD1a-, HECA-, CD123-, S100-, MyogeninD1-, Desmin-, Actin-, Synaptophysin-, Ki-67+ (proliferation rate 60-70%). In addition, the monoclonal antibody NPM1c displayed a strong nuclear and cytoplasmic positivity in most if not all neoplastic cells. FISH analysis The probes (from Vysis) for AML1/ETO, CBF-Beta, MLL, EGR1/D5S23, D5S721, D7S486/CEP7, CEP4, CEP8, CEP11, CEP16 provided negative results. Case 4 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 4 - Figure 1 CD56. Blasts CD56+ Case 4 - Figure 2 CD68. Blasts showing granular positivity for CD68PGM1 Case 4 - Figure 3 CD99. Blasts CD99+ Case 4 - Figure 4 H&E. Large blasts, with round or kidney-shaped nuclei, rather dispersed chromatin, prominent central nucleoli, an a wide rim of cytoplasm Case 4 - Figure 5 GM1. Giemsa stain: fragments of palatine mucosa whose chorion was infiltrated by large blasts Case 4 - Figure 6 GM2. Giemsa stain: large blasts, with round or kidney-shaped nuclei, rather dispersed chromatin, prominent central nucleoli, an a wide rim of cytoplasm Case 4 - Figure 7 LCA. Blasts LCA+ Case 4 - Figure 8 MPO. Blasts were negative for Myeloperoxydase MPO Case 4 - Figure 9 NPM1 LP. Low power field: the monoclonal antibody NPM1c displayed a strong nuclear and cytoplasmic positivity in most if not all neoplastic cells NPM1 HP Case 4 - Figure 10 NPM1 HP. High power field: the monoclonal antibody NPM1c displayed a strong nuclear and cytoplasmic positivity in most if not all neoplastic cells NPM1 LP Case 4 - Figure 11 TdT. Blasts were TdT negative Case 4 - Figure 12 CD123. Blasts were TdT negative Handouts for all Specialty Conferences will be accessible via the "Educational Materials" section on the homepage the morning after each respective conference. Printed copies of the handout will not be available at the meeting.