HISTORY
General Data:
 OR, 24 year-old male, single, living in Cabatuan,
Isabela
Chief complaint:
 Enlarging abdominal mass with sharp pain
HISTORY OF PRESENT ILLNESS
1 month PTA (May 2008)
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

HISTORY OF PRESENT ILNESS
2 weeks PTA
sought consult at a local hospital; UTZ of the
lower abdomen revealed an 18cm mass
 referred to PGH for further management.

HISTORY OF PRESENT ILLNESS
June 2008
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.

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.

FAMILY MEDICAL HISTORY
(+) TB, mother's side
 (-) cryptorchidism
 (-) cancer
 (-) heart disease
 (-) hypertension
 (-) stroke
 (-) diabetes
 (+) asthma

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.

REVIEW OF SYSTEMS

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(+) 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
DIFFERENTIALS
Colon Cancer
Rule In
Rule Out
Palpable abdominal mass
Abdominal pain
Change in bowel habits
Weight loss
Young age
(-) rectal bleeding
(-) signs of anemia
(-) note of change in stool color
Rule In
Rule Out
Urinary Incontinence
Abdominal Pain
Urine Color Abnormal
Dysuria
Palpable
Rule In abdominal mass
(-) hematuria
(-) anemia
(-) fatigue, weakness
(-) pale skin
Urinary Bladder Cancer
Lymphoma
Abdominal mass
Fever
sweats
Weight loss
Testicular Cancer
Rule In
History of cryptochordism
Abdominal mass (testicular lump)
Abdominal discomfort
Rule Out
(-) peripheral adenopathy
(-) fatigue
(-)hepatosplenomegaly
(-) generalized itching
Rule Out
Mass is painful
Cannot be ruled out
DIFFERENTIALS
Inflammatory Bowel Disease (Crohn’s)
Rule In
Abdominal pain
fever
Rule Out
No diarrhea
No fatigability
Cannot be ruled out
Intestinal Obstruction
Rule In
Rule Out
Abdominal pain
Fever
(-) abdominal distention
(-) nausea, vomiting
(-) diarrhea
(-) constipation
(-)
history
Rule
Out of surgery
Young age
(-) nausea, vomiting
Diverticulitis
Rule In
Abdominal pain
Fever
Weight loss
Abdominal Abscess
Rule In
Abdominal pain
Fever
Rule Out
(-) history of abdominal surgery
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
DIFFERENTIALS
Colon Cancer
Rule In
Rule Out
Palpable abdominal mass
Abdominal pain
Change in bowel habits
Weight loss
Rule In
Young age
(-) rectal bleeding
(-) signs of anemia
(-) note of change in stool color
Rule Out
Urinary Incontinence
Abdominal Pain
Urine Color Abnormal
Dysuria
Palpable abdominal mass
Rule In
Abdominal mass
Fever
sweats
Weight loss
(-) hematuria
(-) anemia
(-) fatigue, weakness
(-) pale skin
Rule In
History of cryptochordism
Abdominal mass (testicular lump)
Abdominal discomfort
Rule Out
Mass is painful
Cannot be ruled out
Urinary Bladder Cancer
Lymphoma
Testicular Cancer
Rule Out
(-) peripheral adenopathy
(-) fatigue
(-)hepatosplenomegaly
(-) generalized itching
DIFFERENTIALS
Inflammatory Bowel Disease (Crohn’s)
Rule In
Abdominal pain
fever
Rule Out
No diarrhea
No fatigability
Cannot be ruled out
Intestinal Obstruction
Rule In
Rule Out
Abdominal pain
Fever
(-) abdominal distention
(-) nausea, vomiting
(-) diarrhea
(-) constipation
(-)
history
Rule
Out of surgery
Young age
(-) nausea, vomiting
Diverticulitis
Rule In
Abdominal pain
Fever
Weight loss
Abdominal Abscess
Rule In
Abdominal pain
Fever
Rule Out
(-) history of abdominal surgery
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.
•
ABDOMINAL CT SCAN
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.
BLOOD CHEMISTRY
Result
BUN
Creatinine
Total Bilirubin
Direct Bilirubin
Indirect Bilirubin
Alkaline
Phosphatase
AST
ALT
LDH (done twice)
Sodium
Potassium
Chlorine
Interpretation
12.7 mmol/L
167.7 umol/L
12.5 umol/L
0.5 umol/L
12 umol/L
224 U/L
PGH Normal
Values
2.6-6.4 mmol/L
53-115 umol/L
0-17.1 umol/L
0-5 umol/L
3.4-13.7 umol/L
50-136 U/L
58 U/L
36 U/L
2080 U/L
142 mmol/L
4.2 mmol/L
103 mmol/L
15-37 U/L
35-65 U/L
100-190 U/L
140-148 mmol/L
3.6-5.2 mmol/L
100-108 mmol/L
High
High
High
High
High
SERUM TUMOR MARKERS
* AFP (Alpha-Feto Protein)
* Beta-hCG (Beta Subunit of Human Chorionic Gonadotropin)
* LDH (Lactate Dehydrogenase)
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 alphafetoprotein (AFP) should be treated as
nonseminomas
Patient’s Data:
Taken 10/31/2008
AFP = 1.12 IU/ml (N: 0-11.3 IU/ml)
BETA-HCG
•
In 5-10% of seminoma patients, this may be
elevated; levels may be correlated with
metastasis but not with overall survival
o
If levels do not normalize after orchiectomy, treatment
approach should be that for NSGCT
Patient’s Data:
Taken 10/30/2008
hCG = 141.4 IU/ml (N: 0-5.0 mIU/ml)
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
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.
SUMMARY
S
LDH
hCG† (mIU/mL)
AFP (ng/mL)
Sx
Not assessed
Not assessed
Not assessed
S0
£N
and
Normal
and
Normal
S1
<1.5 x N
and
<5,000
and
<1,000
S2
1.5-10 x N
or
5,000-50,000
or
1,000-10,000
S3
>10 x N
or
>50,000
or
>10,000
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)
Seminoma
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
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
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.
PATHOLOGY OF SEMINOMA
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
PRIMARY TUMOR (T)
REGIONAL LYMPH NODES (N)
DISTANT METASTASIS (M) AND SERUM TUMOR
MARKERS (S)
SERUM TUMOR MARKERS
LDH
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
141.4 IU/ml
1.12 IU/ml
(Normal: 100-190)
(Normal: 0-5)
(Normal: 0-11.3)
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.

1. METASTATIC WORK-UP
Usual pattern of metastasis of seminoma:
TESTS TO ORDER
Examination of the other testicle
 CT of the abdomen
 Chest X-ray
 CT of the chest
 Liver ultrasound

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
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)
Arrests cells in the G2 portion of the cell cycle and induces DNA
2
doses of 500 mg/m
strand breaks by interacting with DNA topoisomerase II and
per cycle
forming free radicals
Cisplatin
(Platinol, Inorganic metal complex thought to act analogously to alkylating
Platinol-AQ)
agents; inhibits DNA synthesis and thus cell proliferation by
doses of 100 mg/m2
causing DNA crosslinks and denaturation of double helix.
per cycle
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 (AlkabanAQ, Velban)
Inhibits microtubule formation, which in turn, disrupts the formation
of mitotic spindle, causing cell proliferation to arrest at
metaphase.
3. RISK DIRECTED CHEMOTHERAPY
Risk
Nonseminoma
Seminoma
Good
Gonadal or retroperitoneal primary site
Absent nonpulmonary visceral metastases
AFP < 1000 ng/mL
Beta-hCG < 5000 mIU/mL
LDH < 1.5 x upper limit or normal (ULN)
Any primary site
Absent
nonpulmonary
visceral metastases
Any LDH, Hcg
Intermediate
Gonadal or retroperitoneal primary site
Absent nonpulmonary visceral metastases
AFP 1000–10,000 ng/mL
Beta-hCG 5000–50,000 mIU/mL
LDH 1.5–10 x ULN
Any primary site
Presence
nonpulmonary
metastases
Any LDH, hCG
Mediastinal primary site
Presence of nonpulmonary visceral
metastases
AFP >10,000 ng/ML
Beta-hCG > 50,000 mIU/mL
LDH > 10 x ULN
No patients classified as
poor prognosis
Poor
of
visceral
ACTUAL MANAGEMENT
November 2008
transferred to the Cancer Institute; set to
receive chemotherapy, but was delayed due to
financial constraints.
 difficulty defecating, difficulty urinating and
anorexia.

HISTORY OF PRESENT ILNESS
January 18, 2009

started first of six cycles of chemotherapy
(Carboplatin, Bleomycin, and Etoposide) every
21 days, each cycle lasting 5 days.
HISTORY OF PRESENT ILLNESS
Recently


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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
ABDOMEN:

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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
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

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.

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
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 postchemotherapy; 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)