Morbidity and Mortality Conference

1. Morbidity and Mortality Conference January 9, 2002 A# 50239521-3 (K1304) Carole Bibeau, MD

2. Initial Presentation • 69 yo WM establishing care at the WRJ VA • Overall felt well • ROS: DOE x 6 months, “dizziness,” easy bruising

3. Past Medical History Diabetes insipidus HTN CVA 1997 PVOD with LE claudication Medications Desmopressin nasal spray qd Amlodipine 10 mg PO qd Benazepril 20 mg PO qd ASA 325 mg PO qd ALLS: NKDA History

4. Social History Married, lived in New London, NH Tobacco: none EtOH: 1 drink/day Retired salesperson for surgical cleaning supply company Family History Mother alive age 94, lived alone, healthy Father deceased age 74, unknown cause Sister alive, well No FHx CAD, DM, cancer Social and Family History

5. Physical Exam Gen: Looks slightly older than stated age VS: BP 110/60 HR 72 wt 160# HEENT: PERRL Card: RRR with occasional early beat; extra sound mid-systole; no S3 or S4; possible diastolic murmur Resp: Clear Abd: Soft, NT, ND, +BS Extr: No edema Neuro: No nystagmus; gait stable

6. Laboratory Data Fe 22 (50-180) TIBC 300 (205-395) Fe saturation 7.3% ESR 33 B12, Folate, Ferritin WNL 11.3 MCV 71 7.8 329 RDW 19.4 N70 L15 M12 E3 2+ anisocytosis, microcytosis, hypochromia 134 102 21 65 4.2 23 1.1 Ca, albumin, LFT’s, TSH, lipids, PSA WNL

7. Two months later... • Follow up visit • Interval history: new ecchymoses on forearms • VS: BP 96/70 HR 56 wt up 3# • Exam: • HEENT: no mucosal bleeding • Card: RRR, systolic murmur • Resp: decreased BS at bases bilaterally • Extr: ecchymoses on forearms • CXR • Echocardiogram

8. Admission to WRJ VAH • Patient admitted for further evaluation • ROS: denied chest pain, tearing sensation, back pain, abdominal pain, SOB at rest, HA, vision change, F/C/S, BRBPR, N/V • Positive for decreased appetite and intermittent constipation x 4 months, estimated 8 pound weight loss

9. Exam Gen: Very pleasant 69 yo WM, A+Ox3, NAD VS: T 96.3 HR 87 BP 108/78 RR 20 sat 98% RA no pulsus HEENT: PERRL, EOMI, op moist, no petechiae Neck: Supple, no LAD, JVP 7 cm, carotids 2+ without bruits Card: RRR, muffled S1; S2 physiologically split, II/VI SEM LLSB Resp: Diminished BS left base Abd: NABS, soft, NT, ND, no bruits Rectal: Nl tone, prostate somewhat enlarged, no masses, soft brown stool, heme positive Extr: Toes cool, femoral pulse 1+ L, 2+ R, no femoral bruits, pedal pulses obtainable via Doppler (monophasic), 1+ pitting ankle edema, multiple small ecchymoses on UE’s Neuro: Grossly non-focal

10. Pericardial effusion Aortic dissection Malignancy Inflammatory process Infectious process Coagulopathy Aortic dilatation Aortic dissection Collagen vascular disease Syphilis Atrial abnormality Thrombus Tumor Anemia, heme positive stools Malignancy Aorto-enteric fistula Assessment and Plan

11. Additional Data Reticulocyte 1.1% ANA POSITIVE 1:320 speckled 1:160 homogeneous RF <20 ANCA (c and p) negative Anti-DS DNA negative RPR negative Blood cx x 1 negative PTT 53.4 PT WNL  THROMBOSIS SCREEN Lupus anticoagulant positive Negative: Anticardiolipin Ab, Factor V Leiden ECG: —NSR 64, nl axis, RBBB (new) —low voltage, no pathologic q’s —ST depressions V2-V6 —non-specific T changes U/A: pH 6.5, s.g 1.015, WNL

12. Consultations/Findings • Colonoscopy • Mass at splenic flexure suspicious for malignancy, near complete obstruction; cannot pass scope beyond it • Path: Adenocarcinoma, moderately differentiated • Rheumatology • +ANA non-specific, likely due to malignancy • Aneurysm not due to aortitis; ?paraneoplastic syndrome • Vascular + CT Surgery • Not feasible to operate • Cardiology • Lipomatous hypertrophy; no further evaluation needed

13. Left Hemicolectomy, HD #10 • Findings • Moderately to poorly differentiated adenocarcinoma, extension to pericolic fat • 11/26 nodes positive, no obvious liver involvement • Tumor-associated thrombosis; start LMWH • Tumor board: offer adjuvant chemo when more stable • Complications (HD #10-23) • Post-op atrial fibrillation with chest pain, hypotension • Delirium • Prolonged ileus • Fluid and electrolyte abnormalities

14. Hypotensive sitting up in chair Telemetry alarm: junctional rhythm with PAC’s, rate 60 Medicine consult requested Medications Metoprolol, desmopressin, heparin SC VS Afebrile BP 92/54, HR 60 irr, RR 24 I>>O, est 8 liters positive Exam Chronically ill appearing JVP 7 Upper airway ronchi, copious frothy sputum Can’t auscultate heart sounds Abd without BS, mildly tender ECG Afib vs junctional rhythm RBBB CXR Early CHF Hospital Day 24 (POD #14)

15. Cardiac HD #28: Afib with RVRIV diltiazem bradycardic with 3-6 second pauses Temporary pacer placed; amiodarone initiated PA catheter placed RV 41/13 PA 41/17 PCWP 30 CI 2.4, SVR 1249 ID HD#24: MRSA in sputum E. faecalis 2/4 bottles in blood; start ampicillin HD#27: Line tip (+) E. faecalis HD#36: Blood cultures neg x 5 days Dispo Transfer back to medicine Hospital Days #28-36

16. Nursing Notes • Hospital Day #35 • “I really felt good before I came in. I thought that I had some minor problem and it would be fixed. I never thought I had all of this going on.” • “I would like to die peacefully and with dignity. Could you see to it that happens?”

17. Transfer to DHMC (HD #41) • Tachy-brady syndrome, symptomatic • Thoracic aortic aneurysm • Pericardial effusion • Pleural effusions • Stage III colon cancer, s/p resection • Lupus anticoagulant, tumor embolus, on anticoagulation • Enterococcal bacteremia, MRSA + sputum • Diabetes insipidus • Deconditioning, prolonged hospitalization (41 days)

18. Medications on Transfer Amiodarone 400 mg PO qd ASA 81 mg PO qd Furosemide 80 mg IV bid Metoprolol 2 mg IV q4hr Spironolactone 25 mg PO qd Ampicillin 2 gm IV q4hr Desmopressin nasal spray bid Ferrous sulfate 325 mg PO tid Magnesium oxide 1 tab PO qd Heparin 5000 u SC bid Rabeprazole 20 mg PO bid PRN: Acetaminophen, albuterol nebs, AlOH/MgOH, docusate, ipratropium nebs, lubriderm, miconazole powder, NTG SL, prochlorperazine

19. Hospital Course (#HD 41-43) • HD #43: DDDR pacer placed • Patient wishes to transfer back to VA

20. Hospital Day #44 • Am VS check: 112 afib, 107/70, RR 30, 80-83% 3 liters, “very wet sounding cough” per nursing. Patient denied SOB. • Team recommended thoracentesis for symptoms • Patient refused care; did not want wife to know • Team discussion with patientCMO instituted • Wife notified of grave situation • Patient died peacefully with wife at bedside • Permission for autopsy granted

21. A-01-153

22. Aorta: Dilated from arch to iliac bifurcation Severe atherosclerosis Aneurysm with mural thrombus

24. Left kidney Right kidney and adrenal

25. Left kidney Right kidney

26. Periadrenal fat Peripancreatic fat

27. Right lung, septum Right lung, pleura

28. Dura: pachymeningitis

29. Dural nodule

30. Right atrium and ventricle, schematic Right atrium and ventricle, A-01-153

31. Right Atrial Lesion

33. Pituitary Stalk

34. Cardiovascular Periaortic Atrial myocardial Pulmonary Pleural Septal Bronchovascular bundles CNS Dural nodules Hypophyseal stalk ?pituitary Retroperitoneal Perirenal Periadrenal peripancreatic Autopsy Finding:Disseminated Xanthogranulomatous process

35. Disseminated Xanthogranulomatous Inflammation:Differential Diagnosis • Infection: Syphilis, atypical mycobacteria, fungi • Malignancy: inflammatory fibrosarcoma, lymphoproliferative disorders • Histiocytoses • Other: inflammatory pseudotumor, lipid storage disorders

36. Histiocytoses • Class I: Langerhans cell histiocytosis • Eosinophilic granuloma, Hand-Schuller-Christian disease, Letterer-Siwe disease • Class II: non-Langerhans cell histiocytosis • Hemophagocytic lymphohistiocytosis (familial erythrophagocytic lymphohistiocytosis), virus-associated hemophagocytic syndrome, sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease), Erdheim-Chester disease, xanthogranuloma, xanthoma disseminatium, reticulohistiocytoma, juvenile xanthogranulomatosis • Class III: malignant histiocytic disorders • Acute monocytic leukemia, malignant histiocytosis, histiocytic lymphoma

37. Langerhans cell Children and juveniles Bone-marrow derived antigen presenting cells not of monocyte/macrophage lineage Immunohistochemical staining: CD1a +, S-100+, CD68 - Non-Langerhans cell Adults: mean age 53 Monocyte-macrophage lineage Immunohistochemical staining: CD1a -, S-100 essentially negative, CD68 + Langerhans vs. Non-Langerhans cell histiocytoses

38. Hemophagocytic lymphohistiocytosis virus-associated hemophagocytic syndrome Rosai-Dorfman disease (sinus histiocytosis with massive lymphadenopathy Erdheim-Chester disease (Lipid granulomatosis) xanthoma disseminatium Reticulohistiocytoma juvenile xanthogranulomatosis xanthogranuloma Non-Langerhans Cell Histiocytoses

39. Histopathology: Infiltration of multiple organ sites by foamy histiocytes, lymphocytesand scattered Touton giantcells with extensive fibrosis Clinical manifestations: Symmetric, sclerotic lesions of long bones dyspnea and respiratory failure due to interstitial lung disease Hydronephrosis and renal failure secondary to retroperitoneal xanthogranulomatosis Diabetes insipidus Extra-axial masses(dural nodules) Retroorbital masses with visual disturbances Ataxia secondary to cerebellar involvement Pericardial infiltration --> pericardial effusion Erdheim-Chester Disease

40. Erdheim-Chester Disease A-01-153 A-95-23