Download CPC - Clinical Correlations

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
• 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
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
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)
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
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
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
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
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
Laboratory Data
MCV 93
134
99
14.6
9
145
4.3
25
11.4
237
0.9
42.3
RDW 13
87N 5L 6M 0E
25
31
39
0.6
4.7
0.2
2.3
Troponin 0.38ng/mL (0.03 to 0.09)
ESR 27mm/60min (0 to 15)
Legionella urine antigen negative
16.2
34.8
1.3
CPK 69 IU/L (38-174)
LDH 233 U/L (91-180)
Admission ECG
Sinus tachycardia, rate 109 bpm, normal axis, normal intervals, otherwise normal ECG
Further Data
• Transthoracic Echocardiogram
– Normal left ventricular size
– Ejection fraction normal (70%)
– Right atrium and ventricle normal size
– Pulmonary artery pressure normal
– No vegetations
Medical Student Presenters
• Histoplasmosis: Allison Chatalbash
• Legionnaires’ disease: Alexis Rodriguez
• Renal cell carcinoma: Yelena Shusterman
• Wegener’s granulomatosis: Daniel Smith
Radiology
Dr. Maria Shiau
Baseline chest radiograph –2/11/05, 2 weeks PTA to outside hospital
Admission chest radiograph (outside hospital) on 2/28/05
Chest radiograph – hospital day 13 (NY Harbor VA day 1) on 3/8/05
Chest computed tomography scan – 3/8/05
Chest computed tomography scan – 3/8/05
Chest computed tomography scan – 3/8/05
Chest computed tomography scan – 3/8/05
Chest computed tomography scan – 3/8/05
Consultant
Dr. David Chong
Pathology
Dr. Rosemary Wieczorek
H&E stain
Beta HCG stain
Electron Microscopy – Rough ER
Electron Microscopy – Glycogen
Additional Images
Dr. Maria Shiau
Amyloid
Metastatic
Melanoma
Wegner’s
Granulomatosis
Wegner’s
Granulomatosis
Aspergillosis
Lymphoma
lymphoma
Final Diagnosis:
Extragonadal Mixed Germ Cell Tumor
(choriocarcinoma plus seminoma)
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
Types of Germ Cell Tumors
• Seminomas (30-40%)
or
• Nonseminomas (60-70%)
–
–
–
–
–
Yolk sac
Embryonal carcinoma
Choriocarcinomas
Teratomas
Nonteratomatous combined GCTs
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
superior vena cava syndrome
postobstructive pneumonia
Dysphagia
vocal cord paralysis
dyspnea
cough
fever / weight loss
shoulder pain
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
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
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
Imaging
• Testicular Ultrasound
– Helps to exclude gonadal primary tumor
• Computed tomography (CT)
– Mature teratomas: heterogeneous, cystic, welldefined 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
Treatment
• Mediastinal GCTs:
– Seminomas: Cisplatin-based chemotherapy
• Bleomycin, etoposide, cisplatin (BEP) x 4 cycles
– Nonseminomas: chemotherapy followed by
surgical excision of residual masses
Gonadal
Carcinoma In Situ
Malignant transformation
Misplaced primordial
germ cell in lung
Increased lung
tumor burden
Elevated LDH
Reverse migration
Hypoxia
Pulmonary nodules
Pleural effusion
Pulmonary infiltrates
Breathlessness
Chest tightness
Cough
Lung crackles
Local inflammation and/or
infection
Elevated ESR
Elevated WBC
Neutrophilia
Fever, tachycardia
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
Patient Follow-up
• Hospital Day #3
– Pathology c/w metastatic carcinoma, poorlydifferentiated (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
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
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. JulAug;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.
Acknowledgements
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•
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•
Dr. Robert Smith
Dr. David Chong
Dr. Maria Shiau
Dr. Rosemary Wieczorek