Seminoma

Background

Seminomas comprise 50% of all testicular germ cell tumors and are most common at 40 years of age. Patients usually present with testicular swelling and pain. Testicular tumors often have elevated serum hCG (human chorionic gonadotropin) in 10% of patients and elevated serum PLAP (placental-like alkaline phosphatase) in 50% of cases. These tumors typically have a cream to yellow cut surface with a buldging fleshy consistency.

INCIDENCE 50% of all testicular tumors

AGE RANGE-MEDIAN Average age 40.5 years
Rare <10 years

EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION

Very tall men

Increased HLA DR5 and Bw41

DISEASE ASSOCIATIONS CHARACTERIZATION

AIDS and immunosuppresion

PATHOGENESIS CHARACTERIZATION

Isochromosome 12p Most common abnormality
May lead to K-ras-2 protoncogene activation

LABORATORY/RADIOLOGIC/
OTHER TESTS
CHARACTERIZATION

Laboratory Markers

Serum hCG
7-25% with mild elevation
10% in stage I patients
25% or more in patients with metastatic disease

Serum LDH
Elevated in 82% of patients with metastatic disease

Serum PLAP
Elevated in 33-91% of stage I patients
Elevated in 40-75% of patients with metastatic disease

Flow cytometry Mean diploid value of 1.6-1.8 times normal

GROSS APPEARANCE/
CLINICAL VARIANTS CHARACTERIZATION

General Right>Left testis
Tumors average 5 cm
Solid well circumscribed and bulge above the surrounding parenchyma
Cut surface tan to cream colored

VARIANTS

Paraneoplastic hypercalcemia Rarely

Exophthalmos Sceondary to paraendocrine abnormality

Current or surgically corrected cryptorchidism 10-30%

HISTOLOGICAL TYPES CHARACTERIZATION

General
There are two cellular elements. There are sheets of seminoma cells with central nuclei, eosinophilic to clear cytoplasm, and large nucleoli. Well defined intercellular borders are present. The second component are numerous lymphocytes occasionally associated with granulomas in 50-60%

About 20% of tumors may have large trophoblast cells, which are immunopositive for HCG. Intermixed with the tumor are broad fibrous bands and septae often infiltrated by lymphocytes.

Necrosis is common

VARIANTS

Tubular variant Closely packed solid tubules

SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHER CHARACTERIZATION

Special stains Glycogen PAS positive

Immunoperoxidase
Positive for PLAP, LDH, ferritin, and NSE
hCG positive in 7-25%
Negative for CD30 and EMA

Necrotic Seminoma of the Testis
Establishing the Diagnosis With Masson Trichrome Stain and Immunostains

Barbara D. Florentine, MD, Arno A. Roscher, MD, Jerry Garrett, MD, and Nancy E. Warner, MD

From the Keck School of Medicine, University of Southern California, Los Angeles, Calif (Drs Florentine, Roscher, and Warner); and Henry Mayo Newhall Memorial Hospital, Newhall, Calif (Drs Florentine, Roscher, and Garrett)
Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 205–206. Abstract quote

We describe an infarcted mass in the testis containing “ghost” cells suspicious for neoplasm. The entire lesion was necrotic.

A Masson trichrome stain greatly improved nuclear and cytologic detail, confirming the suspicion of neoplasm.

Placental alkaline phosphatase revealed specific membrane staining of the neoplastic cells and established a diagnosis of seminoma. Masson trichrome plus selected immunostains offer a promising approach to the diagnosis of certain necrotic neoplasms.

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

CHARACTERIZATION SPERMATOCYTIC SEMINOMA TYPICAL SEMINOMA

Proportion of germ cell tumors 1-2% 40-50%

Sites Testis only Testis, ovary, mediastinum, pineal, retroperitoneum

Bilaterality 9% 2%

Association with other forms of germ cell tumor No Yes

Association with IGCNU No Yes

Intercellular edema Common Uncommon

Composition 3 cell types, with denser cytoplasm, round nuclei 1 cell type, often clear cytoplasm, less regular nuclei

Stroma Scanty Prominent

Lymphoid reaction Rare to absent Prominent

Granulomas Extremely rare Often prominent

Sarcomatous transformation Occasional Absent

Glycogen Absent to scant Abundant

PLAP staining Absent to scant Prominent

hCG staining Absent Present in 10%

Metastases Extremely rare Common

ADDITIONAL DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES

Solid embryonal carcinoma

Solid yolk sac tumor

Choriocarcinoma

Malignant lymphoma

Sertoli cell tumors

PROGNOSIS AND TREATMENT CHARACTERIZATION

Prognostic Factors
The tumor stage is the most important prognostic factor for these tumors with tumors limited to the testis having a survival of >95%.

75% present with disease limited to the testis
20% have retroperitoneal involvement
5% have supradiaphragmatic or organ metastases

Poor prognostic factors:

Vascular invasion-possible
Size>6 cm
Lacking lymphoid stroma
Elevated serum hCG

Survival >95% survival for tumors confined to testis following orchiectomy and radiation

Recurrence Unusual, most occur outside radiated fields in mediastinum, cervical lymph nodes, or lungs

Metastasis 2.5% present with metastases

Treatment
Seminomas are very radiosensitive and respond well to chemotherapy.
Radiation to ipsilateral inguinal and iliac nodes and periaortic and pericaval lymph nodes

Tumors metastatic to retroperitoneum are treated with radiation and may receive platinum based chemotherapy

Tumors of the Testis, Adnexa, Spermatic cord, and scrotum in Atlas of Tumor Pathology. Third Series. Fascicle 25. 1999.

Commonly Used Terms

Testis

Internet Links

Last Updated 3/4/2002

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Copyright � 2002 The Doctor's Doctor

INCIDENCE	50% of all testicular tumors
AGE RANGE-MEDIAN	Average age 40.5 years Rare <10 years

EPIDEMIOLOGIC ASSOCIATIONS	CHARACTERIZATION
Very tall men
Increased HLA DR5 and Bw41

DISEASE ASSOCIATIONS	CHARACTERIZATION
AIDS and immunosuppresion

PATHOGENESIS	CHARACTERIZATION
Isochromosome 12p	Most common abnormality May lead to K-ras-2 protoncogene activation

LABORATORY/RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Laboratory Markers
Serum hCG	7-25% with mild elevation 10% in stage I patients 25% or more in patients with metastatic disease
Serum LDH	Elevated in 82% of patients with metastatic disease
Serum PLAP	Elevated in 33-91% of stage I patients Elevated in 40-75% of patients with metastatic disease
Flow cytometry	Mean diploid value of 1.6-1.8 times normal

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General	Right>Left testis Tumors average 5 cm Solid well circumscribed and bulge above the surrounding parenchyma Cut surface tan to cream colored
VARIANTS
Paraneoplastic hypercalcemia	Rarely
Exophthalmos	Sceondary to paraendocrine abnormality
Current or surgically corrected cryptorchidism	10-30%

HISTOLOGICAL TYPES	CHARACTERIZATION
General	There are two cellular elements. There are sheets of seminoma cells with central nuclei, eosinophilic to clear cytoplasm, and large nucleoli. Well defined intercellular borders are present. The second component are numerous lymphocytes occasionally associated with granulomas in 50-60% About 20% of tumors may have large trophoblast cells, which are immunopositive for HCG. Intermixed with the tumor are broad fibrous bands and septae often infiltrated by lymphocytes. Necrosis is common
VARIANTS
Tubular variant	Closely packed solid tubules

SPECIAL STAINS/IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
Special stains	Glycogen PAS positive
Immunoperoxidase	Positive for PLAP, LDH, ferritin, and NSE hCG positive in 7-25% Negative for CD30 and EMA
Necrotic Seminoma of the Testis Establishing the Diagnosis With Masson Trichrome Stain and Immunostains Barbara D. Florentine, MD, Arno A. Roscher, MD, Jerry Garrett, MD, and Nancy E. Warner, MD From the Keck School of Medicine, University of Southern California, Los Angeles, Calif (Drs Florentine, Roscher, and Warner); and Henry Mayo Newhall Memorial Hospital, Newhall, Calif (Drs Florentine, Roscher, and Garrett)	Arch Pathol Lab Med 2002;Vol. 126, No. 2, pp. 205–206. Abstract quote We describe an infarcted mass in the testis containing “ghost” cells suspicious for neoplasm. The entire lesion was necrotic. A Masson trichrome stain greatly improved nuclear and cytologic detail, confirming the suspicion of neoplasm. Placental alkaline phosphatase revealed specific membrane staining of the neoplastic cells and established a diagnosis of seminoma. Masson trichrome plus selected immunostains offer a promising approach to the diagnosis of certain necrotic neoplasms.

CHARACTERIZATION	SPERMATOCYTIC SEMINOMA	TYPICAL SEMINOMA
Proportion of germ cell tumors	1-2%	40-50%
Sites	Testis only	Testis, ovary, mediastinum, pineal, retroperitoneum
Bilaterality	9%	2%
Association with other forms of germ cell tumor	No	Yes
Association with IGCNU	No	Yes
Intercellular edema	Common	Uncommon
Composition	3 cell types, with denser cytoplasm, round nuclei	1 cell type, often clear cytoplasm, less regular nuclei
Stroma	Scanty	Prominent
Lymphoid reaction	Rare to absent	Prominent
Granulomas	Extremely rare	Often prominent
Sarcomatous transformation	Occasional	Absent
Glycogen	Absent to scant	Abundant
PLAP staining	Absent to scant	Prominent
hCG staining	Absent	Present in 10%
Metastases	Extremely rare	Common

ADDITIONAL DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Solid embryonal carcinoma
Solid yolk sac tumor
Choriocarcinoma
Malignant lymphoma
Sertoli cell tumors

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	The tumor stage is the most important prognostic factor for these tumors with tumors limited to the testis having a survival of >95%. 75% present with disease limited to the testis 20% have retroperitoneal involvement 5% have supradiaphragmatic or organ metastases Poor prognostic factors: Vascular invasion-possible Size>6 cm Lacking lymphoid stroma Elevated serum hCG
Survival	>95% survival for tumors confined to testis following orchiectomy and radiation
Recurrence	Unusual, most occur outside radiated fields in mediastinum, cervical lymph nodes, or lungs
Metastasis	2.5% present with metastases
Treatment	Seminomas are very radiosensitive and respond well to chemotherapy. Radiation to ipsilateral inguinal and iliac nodes and periaortic and pericaval lymph nodes Tumors metastatic to retroperitoneum are treated with radiation and may receive platinum based chemotherapy