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••••••••••••••••••••••••••••••••••Group 1 Case Presentation
abello-bacena
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History
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HISTORY
General Data: OR, 24 year-old male, single, living in
Cabatuan, Isabela
Chief complaint: Enlarging abdominal mass with sharp
pain
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1 month PTA (May 2008)
HISTORY OF PRESENT ILLNESS
Enlarging abdomen with painful, sharp sensation described as “hinihiwa sa tiyan” with concomitant dizziness, cold sweats and fever, resolved upon resting
Intake of unprescribed amoxicillin and mefenamic acid
Pain persisted for 4 days
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2 weeks PTA
HISTORY OF PRESENT ILNESS
sought consult at a local hospital; UTZ of the lower abdomen revealed an 18cm mass
referred to PGH for further management.
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June 2008
HISTORY OF PRESENT ILLNESS
admitted to PGH ward 3, with an enlarged abdomen
decreased appetite, irregular bowel movements (normally once a day, but at that time, he defecated every 2 days), but no difficulty of defecation
weight loss of approximately 4kgs (from 52 to 48 kgs), dysuria, urinary incontinence, and a change in urine color from the usual yellow to white.
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PAST MEDICAL HISTORY
born with both testes undescended; left testes descended at age 6.
(+) mumps during elementary (+) UTI episode (1) when he was 18 or
19 years of age, with concomitant right flank pain. He took unrecalled medications for 7 days with resolution of symptoms.
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FAMILY MEDICAL HISTORY
(+) TB, mother's side (-) cryptorchidism (-) cancer (-) heart disease (-) hypertension (-) stroke (-) diabetes (+) asthma
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PERSONAL-SOCIAL HISTORY
finished 2 years of vocational school and used to work as an electrician
lives with his father, mother and 3 siblings
pays for his chemotherapy with the help of relatives abroad.
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REVIEW OF SYSTEMS (+) weight loss, 4 kgs (-) nausea, vomiting (-) anorexia (+) diarrhea for one week, after chemotherapy (-) constipation (+) dysuria, incontinence (+) numbness of R flank (+) abdominal pain (+) knee pain in the morning upon arising (-) chest pain, palpitations (-) easy fatigability (-) cough
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Differentials
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Colon Cancer
Urinary Bladder Cancer
Lymphoma
Testicular Cancer
Rule In Rule Out
Palpable abdominal massAbdominal painChange in bowel habitsWeight loss
Young age(-) rectal bleeding(-) signs of anemia(-) note of change in stool colorRule In Rule Out
Urinary IncontinenceAbdominal PainUrine Color AbnormalDysuriaPalpable abdominal mass
(-) hematuria(-) anemia(-) fatigue, weakness(-) pale skin
Rule In Rule OutAbdominal massFeversweatsWeight loss
(-) peripheral adenopathy(-) fatigue(-)hepatosplenomegaly(-) generalized itching
Rule In Rule OutHistory of cryptochordismAbdominal mass (testicular lump)Abdominal discomfort
Mass is painfulCannot be ruled out
DIFFERENTIALS
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Inflammatory Bowel Disease (Crohn’s)
Intestinal Obstruction
Diverticulitis
Abdominal Abscess
Rule In Rule OutAbdominal painfever
No diarrheaNo fatigabilityCannot be ruled out
Rule In Rule Out
Abdominal painFever
(-) abdominal distention(-) nausea, vomiting(-) diarrhea(-) constipation(-) history of surgeryRule In Rule Out
Abdominal painFeverWeight loss
Young age(-) nausea, vomiting
Rule In Rule OutAbdominal painFever
(-) history of abdominal surgery
DIFFERENTIALS
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PE
At the time of consult (prior to treatment):
Abdomen: Enlarged abdomen, size consistent with 5-month pregnant
abdomen Mass palpable, ~20cm in largest diameter, at left lower
hemiabdomen
Genitals: Empty scrotal sac on the right Normal testicle on the left, (-) masses/nodules, lesions, tenderness
Essentially normal findings for other systems
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Colon Cancer
Urinary Bladder Cancer
Lymphoma
Testicular Cancer
Rule In Rule Out
Palpable abdominal massAbdominal painChange in bowel habitsWeight loss
Young age(-) rectal bleeding(-) signs of anemia(-) note of change in stool colorRule In Rule Out
Urinary IncontinenceAbdominal PainUrine Color AbnormalDysuriaPalpable abdominal mass
(-) hematuria(-) anemia(-) fatigue, weakness(-) pale skin
Rule In Rule OutAbdominal massFeversweatsWeight loss
(-) peripheral adenopathy(-) fatigue(-)hepatosplenomegaly(-) generalized itching
Rule In Rule OutHistory of cryptochordismAbdominal mass (testicular lump)Abdominal discomfort
Mass is painfulCannot be ruled out
DIFFERENTIALS
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Inflammatory Bowel Disease (Crohn’s)
Intestinal Obstruction
Diverticulitis
Abdominal Abscess
Rule In Rule OutAbdominal painfever
No diarrheaNo fatigabilityCannot be ruled out
Rule In Rule Out
Abdominal painFever
(-) abdominal distention(-) nausea, vomiting(-) diarrhea(-) constipation(-) history of surgeryRule In Rule Out
Abdominal painFeverWeight loss
Young age(-) nausea, vomiting
Rule In Rule OutAbdominal painFever
(-) history of abdominal surgery
DIFFERENTIALS
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Diagnostic Tests
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IMAGING STUDIES
• Scrotal Ultrasound: for any male with suspicious or questionable testicular mass on palpation
• Abdominal and Pelvic CT: to ID metastasis to retroperitoneal LN; also to determine presence of cryptochordism
• Chest CT and Xray: to confirm abnormal chest findings
o In the use of bleomycin, life-threatening pulmonary toxic effects can occur so the drug should be discontinued if early signs of pulmonary toxic effects develop.
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ABDOMINAL CT SCAN
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IN OUR PATIENT…Plain and contrast axial scan of the whole abdomen shows: There is a large solid mass measuring 18.0 x 11.0 x 14.0
cm noted in the peritoneal cavity of with close attachment to the mesentery. There are small packets of contrast with areas of fluid.
The liver is normal in size with low attenuation of the parenchyma.
The gall bladder has no intraluminal densities. The pancreas, and spleen is unremarkable. Both kidneys are normal in size with good function
noted. The prostate is normal in size. The abdominal aorta is unremarkable.
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BLOOD CHEMISTRY
Result PGH Normal Values
Interpretation
BUN 12.7 mmol/L 2.6-6.4 mmol/L HighCreatinine 167.7 umol/L 53-115 umol/L HighTotal Bilirubin 12.5 umol/L 0-17.1 umol/LDirect Bilirubin 0.5 umol/L 0-5 umol/LIndirect Bilirubin 12 umol/L 3.4-13.7 umol/LAlkaline Phosphatase
224 U/L 50-136 U/L High
AST 58 U/L 15-37 U/L HighALT 36 U/L 35-65 U/LLDH (done twice) 2080 U/L 100-190 U/L HighSodium 142 mmol/L 140-148 mmol/LPotassium 4.2 mmol/L 3.6-5.2 mmol/LChlorine 103 mmol/L 100-108 mmol/L
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SERUM TUMOR MARKERS
* AFP (Alpha-Feto Protein)* Beta-hCG (Beta Subunit of Human Chorionic Gonadotropin) * LDH (Lactate Dehydrogenase)
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AFP
• A tumor marker which is elevated when yolk sac elements are present (i.e. nonseminomatous GCT).
• Expected finding (if seminoma): low levels• Tumors that appear to have a seminoma
histology but that have elevated serum levels of alpha-fetoprotein (AFP) should be treated as nonseminomas
Patient’s Data: AFP = 1.12 IU/ml (N: 0-11.3 IU/ml)Taken 10/31/2008
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BETA-HCG
• In 5-10% of seminoma patients, this may be elevated; levels may be correlated with metastasis but not with overall survivalo If levels do not normalize after orchiectomy,
treatment approach should be that for NSGCT
Patient’s Data: hCG = 141.4 IU/ml (N: 0-5.0 mIU/ml) Taken 10/30/2008
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LDH• Less specific for GCTs, but levels
can correlate with overall tumor burden
• Increases in the serum level are influenced primarily by tumor burden and growth rate, cell proliferation and death.
Patient’s Data: LDH = 2080 U/L (N: 100-190 U/L) Taken 10/30/2008
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PLACENTAL ALKALINE PHOSPHATASE (PLAP) PLAP has been distinguished from the common
tissue alkaline phosphatases by its heat resistance, its inhibition by L-phenylalanine, and its immunological properties.
Raised serum concentrations of PLAP are found in seminomas and NSGCT, as well as in ovarian tumors.
Serum values were more frequently elevated in seminoma patients than in nonseminoma patients unless the latter disease was far advanced.
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SUMMARY
>10,000or>50,000or>10 x NS3
1,000-10,000or5,000-50,000or1.5-10 x NS2
<1,000and<5,000and<1.5 x NS1
NormalandNormaland£ NS0
Not assessedNot assessedNot assessedSx
AFP (ng/mL)hCG† (mIU/mL)LDHS
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HISTOLOGY
Patient Results Cell findings were consistent with seminoma;
immunohistochemical staining for PLAP was suggested for confirmation.
There were three specimens submitted: “Abd Mass Core”: cream tan irregular tissue fragments
with an aggregate diameter of 0.5 cm. Block all. “Abd Mass Cell Block”: 20 cc cream white turbid fluid.
For cell block. “Abd Mass FNAB”: 8 unstained slides with smear. For
staining and interpretation
Taken July 19, 2008 (PGH)
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Diagnosis:Seminoma
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PATHOGENESIS OF SEMINOMA
Cryptorchidism - several-fold higher risk of Germ Cell Tumors (GCT) ,~10-40x Abdominal cryptorchid testes > inguinal
cryptorchid testes. Orchiopexy recommended
Testicular feminization - ↑ risk of testicular GCT
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OTHER RISK FACTORS
Trauma Mumps
prenatal exposure to maternal hormones Familial risk for testicular CA
(Hemminki et al, 2004) 4-fold increased risk in a male with a father
who had a GCT 9-fold increased risk if a brother was
affected
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MOLECULAR PATHOGENESIS
An isochromosome of the short arm of chromosome 12 [i(12p)] is pathognomonic for GCT of all histologic types.
Excess 12p copy number occurs in nearly all GCTs, but the genes are still unidentified.
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PATHOLOGY OF SEMINOMA
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COURSE OF THE TUMOR Right testicular tumor
interaortocaval lymph nodes
Left testicular tumor para-aortic lymph nodes
Lymphatic involvement extends cephalad retrocrucal, posterior mediastinal, and supraclavicular lymph nodes
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Staging ofTesticular Cancer
AJCC
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PRIMARY TUMOR (T)
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REGIONAL LYMPH NODES (N)
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DISTANT METASTASIS (M) AND SERUM TUMOR MARKERS (S)
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SERUM TUMOR MARKERSLDH hCG
(mIU/ml)AFP
(ng/ml)
S0 N N N
S1 < 1.5 x N < 5000 < 1000
S2 1.510 x N 5000 – 50,000 1000 – 10,000
S3 > 10 x N > 50,000 > 10,000
Patient’s values 2, 080(Normal: 100-190)
141.4 IU/ml(Normal: 0-5)
1.12 IU/ml(Normal: 0-11.3)
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Initial laboratory results done prior to treatment, as well as the history strongly suggest a diagnosis of testicular carcinoma, seminomatous type.
The stage of the disease, as well as the capacity of the patient will determine the course of treatment.
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Treatment and Management
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1. METASTATIC WORK-UPUsual pattern of metastasis of seminoma:
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TESTS TO ORDER
Examination of the other testicle CT of the abdomen Chest X-ray CT of the chest Liver ultrasound
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2. TREATMENT BASED ON STAGING Treatment
Stage
Extent of Disease Seminoma Nonseminoma
IA Testis only, no vascular/lymphatic invasion (T1)
Radiation therapy RPLND or observation
IB Testis only, with vascular/lymphatic invasion (T2), or extension through tunica albuginea (T2), or involvement of spermatic cord (T3) or scrotum (T4)
Radiation therapy RPLND
IIA Nodes < 2 cm Radiation therapy RPLND or chemotherapy often followed by RPLND
IIB Nodes 2–5 cm Radiation therapy RPLND +/– adjuvant chemotherapy or chemotherapy followed by RPLND
IIC Nodes > 5 cm Chemotherapy Chemotherapy, often followed by RPLND
III Distant metastases Chemotherapy Chemotherapy, often followed by surgery (biopsy or resection)
* Harrison’s Principles of Internal Medicine, 17th edition
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CHEMOTHERAPY DRUGS FOR TESTICULAR CA
Drugs Function
Bleomycin (Blenoxane)
Composed of cytotoxic glycopeptide antibiotics, which appear to inhibit DNA synthesis with some evidence of RNA and protein synthesis inhibition to a lesser degree; used in the management of several neoplasms as a palliative measure.
Etoposide (VP-16)doses of 500
mg/m2 per cycle
Arrests cells in the G2 portion of the cell cycle and induces DNA strand breaks by interacting with DNA topoisomerase II and forming free radicals
Cisplatin (Platinol, Platinol-AQ)
doses of 100 mg/m2 per cycle
Inorganic metal complex thought to act analogously to alkylating agents; inhibits DNA synthesis and thus cell proliferation by causing DNA crosslinks and denaturation of double helix.
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OTHER DRUGS FOR PRIMARY, HIGH-RISK, OR SALVAGE PROTOCOLS
Drugs Function
Ifosfamide (Ifex) Related to nitrogen mustards and is a synthetic analog of cyclophosphamide; inhibits DNA and protein synthesis and thus cell proliferation by causing DNA cross-linking and denaturation of double helix.
Vinblastine (Alkaban-AQ, Velban)
Inhibits microtubule formation, which in turn, disrupts the formation of mitotic spindle, causing cell proliferation to arrest at metaphase.
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3. RISK DIRECTED CHEMOTHERAPY
Risk Nonseminoma Seminoma
Good
Gonadal or retroperitoneal primary siteAbsent nonpulmonary visceral metastasesAFP < 1000 ng/mLBeta-hCG < 5000 mIU/mLLDH < 1.5 x upper limit or normal (ULN)
Any primary siteAbsent nonpulmonary visceral metastasesAny LDH, Hcg
Intermediate
Gonadal or retroperitoneal primary siteAbsent nonpulmonary visceral metastasesAFP 1000–10,000 ng/mLBeta-hCG 5000–50,000 mIU/mLLDH 1.5–10 x ULN
Any primary sitePresence of nonpulmonary visceral metastasesAny LDH, hCG
Poor Mediastinal primary sitePresence of nonpulmonary visceral metastasesAFP >10,000 ng/MLBeta-hCG > 50,000 mIU/mLLDH > 10 x ULN
No patients classified as poor prognosis
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Actual Management
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November 2008
ACTUAL MANAGEMENT
transferred to the Cancer Institute; set to receive chemotherapy, but was delayed due to financial constraints.
difficulty defecating, difficulty urinating and anorexia.
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January 18, 2009
HISTORY OF PRESENT ILNESS
started first of six cycles of chemotherapy (Carboplatin, Bleomycin, and Etoposide) every 21 days, each cycle lasting 5 days.
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Recently
HISTORY OF PRESENT ILLNESS
currently on the second day of the last cycle reported an increase in appetite since
beginning his chemotherapy, return of regular bowel movements and urination
abdominal mass has also visibly reduced in size
In addition to chemotherapy, the patient is on continuous intravenous hydration while undergoing chemotherapy to ensure proper excretion of the drugs
For referral to nephrology for assessment of kidneys after the chemotherapy cycles
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Present P.E. FindingsPost Treatment
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ABDOMEN:
Flat abdomen (-) visible masses, lesions Normoactive bowel sounds (-) tenderness, organomegaly Generally tympanitic, aside from left lower
hemiabdomen Abdominal mass at left lower hemiabdomen: 10cm x 6cm on percussion; 7cm x 6cm on deep
palpation Liver span: 8cm Intact Traube’s space (-) fluid wave, shifting dullness
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GENITALS:
Circumcised (-) penile discharge and lesions along the shaft and
scrotal sac Pubic hair is absent probably due to chemotherapy (-) scrotal swelling or discoloration Empty scrotal sac on the right Left testicle is smooth, non tender and firm;
nontender epididymis (-) inguinal or femoral hernia Nonpalpable inguinal lymph nodes
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Prognosis
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INTERNATIONAL GERM CELL CONSENSUS PROGNOSTIC CLASSIFICATION SYSTEM FOR SEMINOMA
Good Prognosis Any primary site No pulmonary visceral metastases Normal AFP; any hCG or LDH Intermediate Prognosis Testis or retroperitoneal primary site Normal AFP; any hCG or LDH Nonpulmonary visceral metastases
Campbell’s Urology, 8th Ed.
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All stages have at least a 90% cure rate Stage I is 98%-100% Stage II (B1/B2 nonbulky) is 98%-100% Stage II (B3 bulky) and stage III have a 90% complete response
to chemotherapy and an 86% durable response rate to chemotherapy
Second cancers and cardiac disease among long-
term survivors Patients with testicular cancer are at an increased risk of
secondary cancers (malignant mesothelioma and those of the lung, colon, bladder, pancreas, and stomach
Patients with seminoma need counseling and long-term follow-up
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PLANS FOR THE PATIENT
• Check bHCG, LDH: if levels became lower, tx might be working. If not…
• Repeat biopsy (if consistent with NSGCT, use tx approach for NSGCT)
• Repeat CT (to check extent of mass left post-chemotherapy; also, to check for possible metastasis?)
• If with testicular mass, scrotal UTZ• Chest X-ray (if with abn findings, confirm
with chest CT to check for mets)