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

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Presentation on theme: "NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008."— Presentation transcript:

1 NYU Medical Center Department of Medicine Clinical Pathological Conference January 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 Past Medical History –BPH, PUD, diverticulosis, essential tremor Past Surgical History –Multiple hernia repairs, exploratory laparotomy No allergies Medications –Piperacillin/tazobactam, azithromycin, atenolol, ipratropium, albuterol, tylenol with codeine, primidone, finasteride, terazosin

9 Further History (cont) Family history –Mother and Brother with coronary artery disease; Sister with cancer of unknown primary Social history –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 Review of systems –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, SaO % on 100% O2 Bibasilar crackles Tachycardic Obese abdomen Otherwise exam was normal

11 Laboratory Data N 5 L 6 M 0 E MCV 93 RDW 13 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 Admission chest radiograph (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

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24 Consultant Dr. David Chong

25 Pathology Dr. Rosemary Wieczorek

26 H&E stain

27 Beta HCG stain

28 Electron Microscopy – Rough ER

29 Electron Microscopy – Glycogen

30 Additional Images Dr. 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 paindyspnea superior vena cava syndromecough postobstructive pneumoniafever / weight loss Dysphagiashoulder pain vocal cord paralysishoarseness 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 Misplaced primordial germ cell in lung Malignant transformation Increased lung tumor burden Pulmonary nodules Pleural effusion Pulmonary infiltrates Local inflammation and/or infection Fever, tachycardia Elevated WBC Neutrophilia Elevated LDH Breathlessness Chest tightness Cough Elevated ESR Lung crackles Hypoxia Reverse migration

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): Parada D et al. Extragonadal retroperitoneal germ cell tumor: primary versus mestastes? Arch Esp Urol Jul-Aug;60(6): Robertson JH. An unusual tumor presentation. Int Surg Jul- Aug;93(4): Laroira ST et al. Unusual presentations of germ cell tumors: nonseminomatous extragonadal germ cell tumor presenting with pulmonary emboli. J Clin Onc (3): Makhoul I et al. Extragonadal germ cell tumors. June

51 Acknowledgements Dr. Robert Smith Dr. David Chong Dr. Maria Shiau Dr. Rosemary Wieczorek


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