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Clinical Pathological Conference Dr. David Gonzales May 5, 2006

Clinical Pathological Conference Dr. David Gonzales May 5, 2006. CC:  Abdominal pain x 2 months PMH: 49 y/o AAM with h/o abdominal pain x 2 months. Pain is epigastric, constant, severe, disturbs sleep, no radiation, worse with meals and associated with early satiety.

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Clinical Pathological Conference Dr. David Gonzales May 5, 2006

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  1. Clinical Pathological ConferenceDr. David GonzalesMay 5, 2006

  2. CC: Abdominal pain x 2 months PMH: 49 y/o AAM with h/o abdominal pain x 2 months. Pain is epigastric, constant, severe, disturbs sleep, no radiation, worse with meals and associated with early satiety. Associated with nausea, had emesis x 2 two months ago. He reports black stools for 2 weeks but denies BRBPR. He has had poor PO intake and reports losing > 20 lbs over 2 months. He also c/o constipation. No abdominal distention. No jaundice or acholic stools. He denied fever or chills but did say he “felt hot” and had some sweats.

  3. He went to the ER at another facility 2 months ago and was given an unknown medication after X rays and sonogram of the abdomen were done; reportedly negative. His pain worsened and he developed back pain radiating down both lower extremities. He returned to the ER a few weeks later and was given hydrocodone/APAP and a PPI and asked to f/u with a PCP. His PCP continued the PPI but pain persisted. He then developed a new R flank pain, pain radiating down R LE worsened and he complained of R LE weakness. He went back to the ER at the other hospital and after further workup was transferred to our hospital.

  4. PMHx: No PCP H/o MVA x 2 with R elbow #. PSHx: none Allergies: NKDA Medications: Pantoprazole 40 mg po qd Hydrocodone/APAP as needed Social History: Single. Lives with his parents. Will not disclose sexual orientation but has not been sexually active for > 1 year, no h/o STDs. Occasional tobacco-cigars for 3 years, occasional ETOH, denies recreational drug use. Family History: Mother with DM, HTN; Father with HTN ROS: Positive for fatigue, weakness, “feeling hot”, sweats and weight loss as above. Also reports hiccups and R LE weakness , otherwise negative.

  5. PHYSICAL EXAM Gen: emaciated 49 y/o AA male BP 138/92.  HR 111, RR 18, Wt 68.5 kg, T-afebrile HEENT: Normocephalic, atraumatic, PERRL, EOMI, OP clear, slightly dry. Neck- Supple. No JVD, bruit, LAD, thyromegaly. Lungs: CTAB Cv: RRR. S1S2+, no murmur, gallop, rub. Tachycardia+ Abd: Periumbilical and RUQ fullness, Prominent veins above the umbilicus, NABS+. Liver edge palpable, firm, nontender-span 11 cms. Ill defined mass about 8x8 cm palpable in the periumbilical area, lower right border rounded, other borders poorly defined, firm, non tender. No splenomegaly. No shifting dullness. Rectal- Normal sphincter tone. Brown, guaiac –ve stool Neuro: CNS II-XII grossly intact, DTRs 2/4,, sensation intact, F-to-N intact. Strength 5/5 b/l UEs, RLE prox 3+/5, distal 4/5, LLE prox 4/5, distal 4+/5. Gait not evaluated Skin: No rash. Lymphatic: No significant LAD; Ext: Warm, perfused, no LEE. .

  6. Labs 8.3 \ 8.9  / 540        / 27.1 \ N82%, L8%, M6%, E1%,Bands1%, Metamyelocytes 2% Fe <20 ug/dL, ferritin 316 ng/ml, transferrin 171mg/dL, % sat< 8. MCV was 78%, his stool occult blood was initially negative but turned positive 3 days later. RDW 14.9% 129 │98 │23 / 73  Ca 8.6 mg/dL    4.6 │24 │1.7 \ Tp 8.1 g/dL Alb 3.4 g/dL Glob 3.7g/dL AST 78 U/dL  ALT 79 u/dL AlkP 686 u/dL Tbili 0.6 mg/dL • SPEP-protein 6.8-high Alpha 1 globulin 0.32, low albumin FENA< 1           UA-wnl Lipase 1391 U/L, amylase 302 U/L, Uric acid 14.6 mg/dL LDH 2952 U/L , CEA< 0.5 ng/ml, CA 19-9 – 130 U/ml

  7. More tests were ordered….. Fecal H. pylori Antigen -ve;  HIV status +ve; CD4-absolute 110, %- 29% The creatinine and sodium normalized with hydration The alkaline phosphatase dropped to the 190s later.

  8. Radiology: • CXR: Small to moderate left pleural effusion with left basilar atelectasis. • CT Spine- Disc disease L5-S1-no fracture. • Other imaging was obtained…..

  9. CT Abdomen/Pelvis  Massive retroperitoneal adenopathy, Moderate R hydronephrosis, Prominent gastric folds/thickened gastric wall.

  10. A diagnostic procedure was performed….

  11. CPC David Gonzales Presbyterian Hospital of Dallas May 5, 2006

  12. Case presentation • 49 year old male with epigastric pain x 2 months • Constant, severe • Early satiety • 20 pound weight loss, sweats, “feeling hot”

  13. Management of dyspepsia • Unintended weight loss • Persistent vomiting • Dysphagia/Odynophagia • Anemia • Hematemesis • Palpable mass • iron deficiency anemia • Family history of upper gastrointestinal cancer • Previous gastric surgery • Jaundice

  14. Case presentation • Sonogram (-) • No improvement with PPI • Pain extends to right flank and unilateral lower extremity weakness develops • Remainder of history not incredibly helpful

  15. Differential Diagnosis • Tumor • Lymphoma • Biliary or other sites in GI tract • Infection with atypical organism • Gastritis/gastropathy

  16. Physical Exam • Mild tachycardia • Emaciated • Periumbilical/RUQ fullness with firm, 8cm mass; liver palpable • Right leg 3/5 prox, 4/5 distal; left leg 4/5; sensation and reflexes normal

  17. Labs • Microcytic anemia • Ferritin 316 (28-365) • Iron<20, transferrin 171, 8% saturation • Mild thrombocytosis also argues for iron deficiency • Mild hyponatremia and renal insufficiency which corrected with hydration

  18. Labs • Alkaline Phosphatase about 5 x normal with normal bilirubin • Mild transaminitis • Lipase and amylase elevated • Ca 19-9 moderately elevated • LDH and uric acid very elevated

  19. A screening test for plasma cell disorders A clone secretes a homogenous (M for monoclonal) protein If M protein is found, it must be characterized by immunofixation This patient had high alpha-1 globulin and low albumin SPEP

  20. And he’s got AIDS… • CD 4 = 110 • Abdominal pain is common in HIV • Opportunistic infection • Regular stuff (gastritis, cholecystitis, etc) • Medication related • Malignancy

  21. 55 yo AA male with AIDS and • Abdominal pain with fever, weight loss, and sweats • Abdominal mass • Iron-deficiency anemia • Markers of high cell turnover • Pancreaticobiliary abnormalities

  22. Imaging • CXR: small left pleural effusion with atelectasis • CT Abdomen/Pelvis • Massive retroperitoneal adenopathy • Moderate R hydronephrosis • Prominent gastric folds • No info on liver, pancreas, or kidney: assume normal

  23. Retroperitoneal Adenopathy • Retroperitoneal fibrosis • Testicular Cancer • Renal Cell Carcinoma • Opportunistic infection • Lymphoma

  24. Enlarged Gastric Folds • Menetrier’s disease • Foveolar hyperplasia in the body and fundus of the stomach • Symptoms include pain, asthenia, anorexia • Often have hypoalbuminemia secondary to protein-losing enteropathy

  25. Enlarged Gastric folds • Zollinger-Ellison (gastrinoma) • High gastrin output causes acid hypersecretion  ulcers, primarily in the duodenum and distally • Often associated with diarrhea (3/4 of pts) • Weight loss only present in 17% • MEN 1

  26. Enlarged Gastric Folds • H. Pylori-associated gastritis • Anisakiasis • Adenocarcinoma • Lymphoma • GI vs. HIV-related

  27. Gastrointestinal lymphoma • Defined as localized disease in the GI tract or presentation predominantly in the GI tract • Role of MALT • Spread from adjacent nodes • Diffuse large B-cell lymphoma also seen

  28. HIV and malignancy • Increased incidence similar to transplant recipients • Length and degree of immunosuppression likely play roles • Role of HIV and other viruses including EBV

  29. HIV and lymphoma • Risk increases directly as CD4 count drops • 3 General types • Primary CNS lymphoma • Primary effusion lymphoma • Non-Hodgkin’s lymphoma

  30. HIV and systemic lymphoma • Tend to be aggressive • High proliferation • Spontaneous cell death • 2 main histologic types • Diffuse large B cell • Burkitt’s or Burkitt’s-like

  31. Burkitt’s lymphoma • 3 types • Endemic (African) • Non-endemic (American) • Immunodeficient • Translocation of C-myc is important

  32. To summarize • 55 year old male with AIDS • Abdominal pain from a large, fast-growing retroperitoneal mass • B symptoms (probably) • Evidence of high cell turnover (uric acid and LDH • LE motor weakness and R hydronephrosis • Suspect nerve root and ureteral compression from adenopathy

  33. Summary • Diagnostic test: lymph node biopsy • EUS?

  34. Diagnosis • AIDS-associated NHL, favor Burkitt’s • Rapid presentation • High cell turnover • Rare

  35. M.C. Diffuse high grade B-cell lymphoma, Burkitt- like morphology 2/1/06 Retroperitoneal core biopsy 2/1/06 Bone marrow biopsy 2/2/06 Duodenal mass biopsy Gastric mass biopsy 2/2/06 CSF cytology

  36. M.C. Pathology • Diffuse infiltrate B-cells (CD20+) • Uniform intermediate size nuclei • Fine chromatin, nucleoli present • Basophilic cytoplasm with vacuoles • Numerous mitoses, admixed histiocytes

  37. M.C. Immunophenotype Positive: CD20, CD79, CD10, Bcl-6, CD38 Negative: CD34, CD117, CD3, Tdt, Bcl-2, CD138, CD5, CD23, CD56 Light chain restriction: Kappa Ki-67 proliferative index = high (> 90%)

  38. M.C. Diagnosis • Diffuse high grade B-cell lymphoma, Burkitt-like morphology • Definitive diagnosis pending FISH studies for c-myc translocation • c-myc FISH results • 1st lab: negative • 2nd lab: positive

  39. FISH LSI IGH/MYC, CEP 8 LSI MYC break apart

  40. Classic Burkitt’s lymphoma Morphology • Diffuse, monomorphic cells • Interspersed macrophages – “starry sky” • Neoplastic nuclei are uniform, round intermediate size • Multiple (2-5) small distinct nucleoli – uniform • Moderate amount basophophilic vacuolated cytoplasm • Frequent mitoses, apoptotic bodies

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