Download - NYU Medical Center Department of Medicine Clinical Pathological Conference January 18, 2008
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NYU Medical CenterDepartment of Medicine
Clinical Pathological ConferenceJanuary 18, 2008
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Chief Complaint
• 77 year-old man with acute breathlessness and productive cough for eight days
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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
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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
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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)
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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
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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
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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
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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
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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
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Laboratory Data
134
4.3
99
25
9
0.9
145
25
31
390.6
0.2
4.7
2.3
16.2 34.8
1.3
11.4 237
14.6
42.3
87N 5L 6M 0E
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
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Admission ECG
Sinus tachycardia, rate 109 bpm, normal axis, normal intervals, otherwise normal ECG
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Further Data
• Transthoracic Echocardiogram– Normal left ventricular size– Ejection fraction normal (70%)– Right atrium and ventricle normal size– Pulmonary artery pressure normal– No vegetations
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Medical Student Presenters
• Histoplasmosis: Allison Chatalbash
• Legionnaires’ disease: Alexis Rodriguez
• Renal cell carcinoma: Yelena Shusterman
• Wegener’s granulomatosis: Daniel Smith
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Radiology
Dr. Maria Shiau
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Baseline chest radiograph –2/11/05, 2 weeks PTA to outside hospital
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Admission chest radiograph (outside hospital) on 2/28/05
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Chest radiograph – hospital day 13 (NY Harbor VA day 1) on 3/8/05
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Chest computed tomography scan – 3/8/05
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Chest computed tomography scan – 3/8/05
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Chest computed tomography scan – 3/8/05
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Chest computed tomography scan – 3/8/05
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Chest computed tomography scan – 3/8/05
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Consultant
Dr. David Chong
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Pathology
Dr. Rosemary Wieczorek
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H&E stain
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Beta HCG stain
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Electron Microscopy – Rough ER
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Electron Microscopy – Glycogen
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Additional Images
Dr. Maria Shiau
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Amyloid
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Metastatic Melanoma
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Wegner’s
Granulomatosis
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Wegner’s
Granulomatosis
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Aspergillosis
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Lymphoma
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lymphoma
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Final Diagnosis:
Extragonadal Mixed Germ Cell Tumor
(choriocarcinoma plus seminoma)
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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
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Types of Germ Cell Tumors
• Seminomas (30-40%)or
• Nonseminomas (60-70%)
– Yolk sac – Embryonal carcinoma – Choriocarcinomas– Teratomas– Nonteratomatous combined GCTs
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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 pneumoniafever / 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
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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
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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
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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
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Treatment
• Mediastinal GCTs:– Seminomas: Cisplatin-based chemotherapy
• Bleomycin, etoposide, cisplatin (BEP) x 4 cycles
– Nonseminomas: chemotherapy followed by surgical excision of residual masses
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GonadalCarcinoma In Situ
Misplaced primordialgerm cell in lung
Malignant transformation
Increased lungtumor burden
Pulmonary nodulesPleural effusion
Pulmonary infiltrates
Local inflammation and/orinfection
Fever, tachycardia
Elevated WBCNeutrophilia
Elevated LDH
BreathlessnessChest tightness
Cough
Elevated ESR
Lung crackles
Hypoxia
Reverse migration
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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
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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
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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
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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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Acknowledgements
• Dr. Robert Smith
• Dr. David Chong
• Dr. Maria Shiau
• Dr. Rosemary Wieczorek