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NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008. Chief Complaint. 77 year-old man with acute breathlessness and productive cough for eight days. History of Present Illness.

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NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008

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  1. NYU Medical CenterDepartment of MedicineClinical Pathological ConferenceJanuary 18, 2008

  2. Chief Complaint • 77 year-old man with acute breathlessness and productive cough for eight days

  3. History of Present Illness • 50 years PTA – patient started smoking 2 packs of cigarettes daily and consumed 1 quart of alcohol daily x 40 years • diagnosed with hypertension • 6 years PTA – intermittent hematuria • Cystoscopy with bladder biopsies showed bladder diverticulum, no malignancy • 1 year PTA – developed breathlessness which worsened with exertion but did not seek medical attention

  4. History of Present Illness (cont) • ~4 weeks PTA: • Developed cough, CXR was reported as normal • 12 days PTA: • Admitted to an outside hospital with 3 days of gross hematuria and flank tenderness • CXR showed bilateral lower lung field infiltrates and bilateral pulmonary nodules • At outside hospital: • Treated for Enterococcus UTI • Abdominal CT scan negative for LAN, hydronephrosis, urothlithiasis or other pelvic abnormalities

  5. History of Present Illness (cont) • 8 days PTA: • Developed acute breathlessness, chest tightness, productive cough • Empirically treated for pneumonia • Chest CT – multiple pulmonary nodules and small bilateral pleural effusions • Sputa negative for AFB smear (3 samples)

  6. History of Present Illness (cont) • 4 days PTA: • Bronchoscopy was performed, BAL negative for AFB, positive for Candida albicans • Transbronchial biopsy of lower lung parenchyma – focal hemorrhage and small lymphocytic infiltration; rare single large atypical cells and macrophages • Gomori methenamine silver and gram stain – small intracellular material in macrophages

  7. History of Present Illness (cont) • The patient’s respiratory status slowly declined over the following 4 days • He was transferred to the NY Harbor VA hospital for further workup • A procedure was perfomed

  8. Further History • PastMedicalHistory • BPH, PUD, diverticulosis, essential tremor • PastSurgicalHistory • Multiple hernia repairs, exploratory laparotomy • No allergies • Medications • Piperacillin/tazobactam, azithromycin, atenolol, ipratropium, albuterol, tylenol with codeine, primidone, finasteride, terazosin

  9. Further History (cont) • Familyhistory • Mother and Brother with coronary artery disease; Sister with cancer of unknown primary • Socialhistory • Born in the US, lived with his wife, retired maintenance worker • Korean War veteran • 80 pack years tobacco use; 40 years alcohol abuse • No illicit drug use • Reviewofsystems • Otherwise negative

  10. Physical Exam • Elderly man lying in bed in respiratory distress but able to answer questions • T 100.5ºF, HR 103 bpm, BP 103/56mmHg • RR 22-26/min, SaO2 85-95% on 100% O2 • Bibasilar crackles • Tachycardic • Obese abdomen • Otherwise exam was normal

  11. MCV 93 14.6 134 99 9 11.4 237 145 4.3 25 0.9 42.3 RDW 13 87N 5L 6M 0E 25 0.6 4.7 16.2 34.8 39 31 0.2 2.3 1.3 Laboratory Data Troponin 0.38ng/mL (0.03 to 0.09) CPK 69 IU/L (38-174) ESR 27mm/60min (0 to 15) LDH 233 U/L (91-180) Legionella urine antigen negative

  12. Admission ECG Sinus tachycardia, rate 109 bpm, normal axis, normal intervals, otherwise normal ECG

  13. Further Data • Transthoracic Echocardiogram • Normal left ventricular size • Ejection fraction normal (70%) • Right atrium and ventricle normal size • Pulmonary artery pressure normal • No vegetations

  14. Medical Student Presenters • Histoplasmosis: Allison Chatalbash • Legionnaires’ disease: Alexis Rodriguez • Renal cell carcinoma: Yelena Shusterman • Wegener’s granulomatosis: Daniel Smith

  15. Radiology Dr. Maria Shiau

  16. Baseline chest radiograph –2/11/05, 2 weeks PTA to outside hospital

  17. Admissionchestradiograph (outside hospital) on 2/28/05

  18. Chest radiograph – hospital day 13 (NY Harbor VA day 1) on 3/8/05

  19. Chest computed tomography scan – 3/8/05

  20. Chest computed tomography scan – 3/8/05

  21. Chest computed tomography scan – 3/8/05

  22. Chest computed tomography scan – 3/8/05

  23. Chest computed tomography scan – 3/8/05

  24. ConsultantDr. David Chong

  25. Pathology Dr. Rosemary Wieczorek

  26. H&E stain

  27. Beta HCG stain

  28. ElectronMicroscopy – Rough ER

  29. Electron Microscopy – Glycogen

  30. Additional ImagesDr. Maria Shiau

  31. Amyloid

  32. Metastatic Melanoma

  33. Wegner’s Granulomatosis

  34. Wegner’s Granulomatosis

  35. Aspergillosis

  36. Lymphoma

  37. lymphoma

  38. Final Diagnosis: Extragonadal Mixed Germ Cell Tumor (choriocarcinoma plus seminoma)

  39. Extragonadal Germ Cell Tumors(EGGCT) • Represent only 1 to 5% of all GCTs • Usually arise from a midline point of origin: • Anterior mediastinum (50-70%) • Retroperitoneum (30-40%) • Pineal gland (5%) • Sacrococcyx (<5%) • May also represent metastasis of occult carcinoma in situ (CIS) in the gonad with reverse migration • Genetically similar to primary gonadal tumors

  40. Types of Germ Cell Tumors • Seminomas(30-40%)or • Nonseminomas(60-70%) • Yolk sac • Embryonal carcinoma • Choriocarcinomas • Teratomas • Nonteratomatous combined GCTs

  41. Mediastinal Germ Cell Tumors • Most common site of EGGCTs, either mature teratomas (60-70%) or malignant (30-40%) • Malignant MGCTs = seminomas (40%) or nonseminomas (60%) • Symptoms include: • chest pain dyspnea • superior vena cava syndrome cough • postobstructive pneumonia fever / weight loss • Dysphagia shoulder pain • vocal cord paralysis hoarseness • Metastases to local lymph nodes or to distant sites, such as the lungs, liver, or bone, may be present in 20-50% of cases on presentation

  42. Extragonadal Germ Cell Tumors • Pulmonary parenchyma is a rare primary site • Prognosis depends on histology and location of primary site • Overall 5-year survival: 40-65% • Best survival rates with extragonadal seminomas

  43. Laboratory Studies • Human chorionic gonadotropin (bhCG) • Elevated in choriocarcinoma and embryonal carcinoma • Prostate, bladder, ureteral, and renal carcinomas • Alpha fetoprotein (AFP) • Elevated in yolk sac and embyronal carcinoma • NOT produced by pure seminomas or pure choriocarcinomas • Pregnancy, hepatocellular carcinoma, cirrhosis, hepatitis • LDH – nonspecific, correlates with tumor burden

  44. Imaging • Testicular Ultrasound • Helps to exclude gonadal primary tumor • Computed tomography (CT) • Mature teratomas: heterogeneous, cystic, well-defined anterior mediastinal masses +/- calcifications • Seminoma MGCT: bulky, lobulated, homogeneous anterior mediastinal masses, calcification rare • Nonseminoma MGCT: irregular anterior mediastinal masses with low attenuation and adjacent organ involvement

  45. Treatment • Mediastinal GCTs: • Seminomas: Cisplatin-based chemotherapy • Bleomycin, etoposide, cisplatin (BEP) x 4 cycles • Nonseminomas: chemotherapy followed by surgical excision of residual masses

  46. Gonadal Carcinoma In Situ Malignant transformation Misplaced primordial germ cell in lung Reverse migration Increased lung tumor burden Elevated LDH Hypoxia Pulmonary nodules Pleural effusion Pulmonary infiltrates Elevated ESR Breathlessness Chest tightness Cough Elevated WBC Neutrophilia Local inflammation and/or infection Lung crackles Fever, tachycardia

  47. Patient Follow-up • Hospital Day #1 (total hospital day 13) • Amphotericin was started for fungal coverage and antibacterials were stopped • Repeat chest CT showed multiple pulmonary nodules and bilateral pleural effusions • Hospital Day #2 • Open lung biopsy was performed • Pleural fluid: 9 WBC (59% segs, 29% lymphs, 12% macrophages), 70,000 RBC, no malignant cells • HIV test negative • NSTEMI post-procedure

  48. Patient Follow-up • Hospital Day #3 • Pathology c/w metastatic carcinoma, poorly-differentiated (favored adenocarcinoma) • Amphotericin was discontinued • Hospital Days #4-6 • Oncology work-up was initiated with repeat physical exam • Left testicle noted to be larger in size than right side but without nodule • Urine beta-hCG positive • Quantitative HCG 2318 mIU/ml (0 to 5) • Alpha-fetoprotein negative • Scrotal U/S showed hydrocele but no testicular mass

  49. Patient Follow-up • Hospital Days #6-9 • Clinical status deteriorated • Immunopathology positive for HCG, but AFP negative • Consistent with mixed germ cell tumor composed of choriocarcinoma and seminoma • Hospital Days #10-20 • Started chemotherapy with cisplatin-based regimen for five days • No improvement in hypoxemia or radiographic findings • Progressive multiorgan failure • The patient expired one week after completing chemotherapy

  50. References Malagon HD et al. Germ cell tumors with sarcomatous components: a clinicopathologic and immunohistochemical study of 46 cases. Am J Surg Pathol 2007.Sep;31(9):1356-62. Parada D et al. Extragonadal retroperitoneal germ cell tumor: primary versus mestastes? Arch Esp Urol 2007. Jul-Aug;60(6):713-19. Robertson JH. An unusual tumor presentation. Int Surg 2007. Jul-Aug;93(4):218-20. Laroira ST et al. Unusual presentations of germ cell tumors: nonseminomatous extragonadal germ cell tumor presenting with pulmonary emboli. J Clin Onc 2001. 19(3):915-6. Makhoul I et al. Extragonadal germ cell tumors. http://www.emedicine.com/MED/topic759.htm. June 2004.

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