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.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/
Other Diagnostic Testing
and Clinical Variants
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE 50% of all testicular tumors AGE RANGE-MEDIAN Average age 40.5 years
Rare <10 years
DISEASE ASSOCIATIONS CHARACTERIZATION AIDS and immunosuppresion Very tall men Increased HLA DR5 and Bw41
PATHOGENESIS CHARACTERIZATION Isochromosome 12p Most common abnormality
May lead to K-ras-2 protoncogene activation
CHARACTERIZATION Laboratory Markers Serum hCG 7-25% with mild elevation
10% in stage I patients
25% or more in patients with metastatic disease
Prognostic value of BHCG and local tumor invasion in stage I seminoma of the testis.
Schwartz BF, Auman R, Peretsman SJ, Moul JW, Deshon GE, Hernandez J, Rozanski RA, Thrasher JB.
Department of Urology, Madigan Army Medical Center, Tacoma, Washington 98431-5000, USA.
J Surg Oncol 1996 Feb;61(2):131-3 Abstract quote
Approximately 10-15% of patients with stage 1 pure seminoma of the testis have an elevated preorchiectomy serum beta human chorionic gonadotropin level [1-4]. The prognostic significance of this elevation is unknown.
We performed a multi-institutional retrospective review of 332 men with stage I pure seminoma of the testis and evaluated the prognostic significance of this elevation and the prognostic value of local invasion of the primary tumor. Twenty-five of 191 evaluable patients (13%) had elevated preorchiectomy beta human chorionic gonadotropin. All normalized postoperatively and are alive without evidence of disease with a median follow-up of 50 months (range 1-124 mo). Of 191 patients, 190 (99.5%) are alive and free of disease. One patient underwent salvage chemotherapy for a chest recurrence, and he is alive and free of disease at 72 months.
We conclude that elevated preorchiectomy serum beta human chorionic gonadotropin level and local invasion of the primary tumor do not portend a poor prognosis in patients with clinical stage I pure seminoma of the testis.
Significance of simultaneous determination of serum human chorionic gonadotropin (hCG) and hCG-beta in testicular tumor patients.
Hoshi S, Suzuki K, Ishidoya S, Ohyama C, Sato M, Namima T, Saito S, Orikasa S.
Department of Urology, Tohoku University School of Medicine, Sendai, Japan.
Int J Urol 2000 Jun;7(6):218-23 Abstract quote
BACKGROUND: Simultaneous determinations of human chorionic gonadotropin hormone (hCG) and hCG-beta frequently produce discrepancies, that is when hCG or hCG-beta is normal, the other is elevated. Accordingly, we examined the significance of simultaneous determination of serum hCG and hCG-beta in testicular tumors.
METHODS: Simultaneous determination of hCG and hCG-beta was performed in 54 patients with testicular seminoma and 74 with non-seminomatous testicular tumors.
RESULTS: For detection of seminoma patients, hCG-beta was more effective than hCG because hCG-beta was positive in 83% (45/54) of the patients and hCG was positive in 50% (27/54). In non-seminomatous testicular tumor cases, hCG-beta was positive in 74% (55/74) and hCG was positive in 82% (61/74). The cases of hCG<1.0 mIU/mL and HCG-beta>0.1 ng/mL were significantly more frequently seen in patients with seminoma than in those with non-seminomatous testicular tumor (P < 0.001). Fourteen patients had recurrent tumor. At recurrence, only hCG was elevated in nine cases, only hCG-beta was elevated in two cases and both in one case. For diagnosis of falsely positive hCG, testosterone administration was effective because after testosterone administration, serum hCG levels became undetectable (< 1.0 mIU/mL) within one week in three examined cases.
CONCLUSION: Human chorionic gonadotropin-beta was a better marker of seminoma than hCG. For earlier detection of recurrence, both markers should be examined. For diagnosis of falsely positive hCG, testosterone administration was effective.
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
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 INTERTUBULAR (INTERSTITIAL)
Hum Pathol. 2005 Jun;36(6):640-5. Abstract quote
Summary Clinical stage I seminomas are effectively treated with surgery raising concerns as to when to give adjuvant radiation therapy given the risk of secondary malignancies. A recent randomized trial found tumor size and rete testis invasion to be the strongest predictors of relapse in clinical stage I seminomas. These 2 parameters may be surrogate measures of tumor volume.
Intertubular seminoma (ITS) of the testis describes the presence of neoplastic germ cells within the interstitium of the testis. These cells are detected away from the main macroscopic mass. Because ITS can infiltrate in a 3-dimensional fashion, it may also represent a measure of tumor volume not usually noted in standard pathology reporting.
The goal of this study was to determine the incidence of ITS in pure seminomas and its association with other prognostic parameters. One hundred twenty consecutive pure seminomas surgically removed between 1998 and 2003 were evaluated. ITS was defined as the presence of an interstitial or intertubular growth pattern of tumor cells, which was noncontiguous with the main tumor and present at least 3 high-power fields away from the tumor mass. The average tumor size was 3.4 cm. Of the entire cohort of patients, which included pathological stages T1 through T3, 11% had invasion through the tunica albuginea, 51% had rete testis invasion, 51% had lymphovascular invasion, 93% had associated intratubular germ-cell neoplasia, and 36% had ITS. ITS was significantly associated with rete testis invasion ( P = .001). Logistic regression analysis looking at ITS, tumor size, patient age, and lymphovascular invasion revealed that only ITS was associated with rete testis invasion (RR, 4.1, P < .0001). ITS is present in a significant proportion of pure seminomas and has a significant association with rete testis invasion.
The presence of ITS may therefore be an important prognostic factor, not only because it alters the calculated size of the tumor but also because it has an association with rete testis invasion.
Seminomas With Exclusive Intertubular Growth: A Report of 12 Clinically and Grossly Inconspicuous Tumors.
Henley JD, Young RH, Wade CL, Ulbright TM.
*Department of Pathology, Indiana University School of Medicine, Indianapolis, IN; and the daggerJames Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2004 Sep;28(9):1163-1168. Abstract quote
Intertubular growth in seminoma is characterized by seminoma cells, either singly or in small clusters, between preserved seminiferous tubules. It is a common, although focal, pattern in many seminomas where it is admixed with the usual sheet-like and nested arrangements and does not pose any diagnostic problems in such cases.
We describe, in contrast, the clinicopathologic features of 12 cases with exclusively intertubular growth and which were typically diagnostically problematic. The 12 patients lacked overt clinical signs of a primary testicular mass. Three presented with infertility, 2 with cryptorchidism, 2 with metastases, 1 with pain and testicular atrophy, and the presentation was unknown in 4.
On gross examination, no mass was apparent in 9 cases with available data, but ill-defined firm areas or foci of whitish-brown discoloration were occasionally noted.
Microscopically, the process was characterized by individual, dispersed tumor cells or small clusters of cells growing between the seminiferous tubules. The tumor cells were often obscured by a lymphocytic infiltrate or, less commonly, nodules of hyperplastic Leydig cells. Common associated findings were tubular atrophy with sclerosis and thickening of tubular basement membranes and intratubular germ cell neoplasia, unclassified type.
Immunostains against placental-like alkaline phosphatase and c-KIT (CD117) highlighted the seminoma cells in all cases examined.
In pure form, intertubular seminoma is both clinically and pathologically inconspicuous and may be misdiagnosed as atrophy, scar, or orchitis.
Hum Pathol. 2006 Apr;37(4):458-61. Epub 2006 Mar 6. Abstract quote
Intratubular seminoma (ITS) has been defined as the complete filling of the seminiferous tubules with seminoma cells with no Sertoli cells present. This contrasts with intratubular germ cell neoplasia, unclassified (IGCNU), where the malignant germ cells are interspersed by Sertoli cells.
We aimed to determine the relationship between these 2 entities and the association between ITS and invasive classic seminomas. We therefore examined the morphology and immunochemistry of ITS and IGCNU adjacent to germ cell tumors to differentiate the patterns, frequency, and distribution of these lesions. We found that ITS was seen in equal frequency adjacent to seminomas as it was to nonseminomas. The presence of ITS in non-seminomatous germ cell tumors suggests that it is a true in situ lesion rather than representative of intratubular spread of an existing seminoma.
However, because it is not specifically associated with seminoma, we suggest that it is not useful to discriminate this lesion from IGCNU and that it merely represents an advanced form of IGCNU on the way to invasive malignancy.
- The Frequency and Distribution of Intratubular Trophoblast in Association With Germ Cell Tumors of the Testis.
Berney DM, Lee A, Shamash J, Oliver RT.
From the Departments of *Histopathology and Morbid Anatomy and daggerMedical Oncology, St. Bartholomew's & the Royal London School of Medicine & Dentistry, Queen Mary University of London, St. Bartholomew's Hospital, West Smithfield, London, UK.
Am J Surg Pathol. 2005 Oct;29(10):1300-1303. Abstract quote
Although the presence of intratubular trophoblast (ITT) has been reported, its frequency and distribution in association with germ cell tumors (GCT) have not been investigated. Beta human chorionic gonadotropin (hCG) is a sensitive immunohistochemical marker of syncytiotrophoblast.
We therefore wished to investigate whether intratubular trophoblastic elements could be identified adjacent to invasive tumors using immunohistochemistry against hCG. Seventy-five GCTs were examined. Immunochemistry was performed for hCG. Both invasive tumor and seminiferous tubules were examined for positive staining. The seminomas showed ITT in five of 29 cases. All these cases had trophoblastic cells as part of the invasive tumor. Only one of 36 cases of nonseminoma and one of nine of the mixed GCTs (11%) showed ITT. Again, all of the positive cases had hCG-positive trophoblastic cells within the invasive tumor. ITT can be identified adjacent to GCTs in a significant number of cases.
We suggest that this is a genuine in situ lesion, associated with seminomas with syncytiotrophoblastic cells. Differentiation toward trophoblastic elements in GCTs may occur at an earlier stage of their pathogenesis than has been previously recognized.
TUBULAR Closely packed solid tubules
Seminoma With Tubular, Microcystic, and Related Patterns: A Study of 28 Cases of Unusual Morphologic Variants That Often Cause Confusion With Yolk Sac Tumor.
Ulbright TM, Young RH.
From the *Department of Pathology, Indiana University School of Medicine, Indianapolis, IN; and the daggerJames Homer Wright Pathology Laboratories, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Am J Surg Pathol. 2005 Apr;29(4):500-505. Abstract quote
We report 28 testicular seminomas with cystic spaces of variable nature, sometimes accompanied by solid and hollow tubular patterns (12 cases). The spaces often suggested reticular or microcystic patterns of yolk sac tumor, and the solid and hollow tubular patterns often added to the diagnostic confusion. The tumors occurred in men 21 to 55 years old and on gross examination had the typical appearance of seminoma.
On microscopic examination, the spaces ranged from small, closely packed and relatively regular to dilated, more dispersed and somewhat irregular. The hollow tubules appeared to result from central discohesion within nests of tumor. The spaces, particularly when large, often contained occasional tumor cells or inflammatory cells within pale edema fluid. The cytologic appearance of the cells lining the spaces, and in the surrounding tumor, retained the typical features of seminoma cells. Thirteen tumors (46%) either lacked (8 cases) or had very scant (5 cases) lymphocytes in the cystic and tubular areas, and hyaline globules were absent. Thirteen of 13 tumors were immunopositive for OCT-3/4 in the nontypical and typical areas; 9 of 10 were placental alkaline phosphatase positive, and 7 of 10 were c-Kit (CD117) positive. The same 13 cases were negative with cytokeratin (AE1/AE3) and alpha-fetoprotein stains.
Distinction from yolk sac tumor is aided by the observation that the spaces of yolk sac tumor are often more irregular in their individual shapes and frequently form anastomosing channels. Additionally, the spaces of yolk sac tumor randomly merge with various other yolk sac tumor patterns. The cells lining spaces in yolk sac tumor are often flattened with compressed nuclei and lack the typical prominent nucleoli of seminoma cells. Paucity of lymphocytes and intracystic edema, however, are not differentially helpful, although basophilic fluid favors yolk sac tumor.
A panel of immunostains (AE1/AE3, OCT-3/4, and alpha-fetoprotein) is helpful in the differential with yolk sac tumor in especially problematic cases. The edema and paucity of lymphocytes may suggest spermatocytic seminoma, but the varied cell types of that neoplasm are absent.
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. 205206. 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.
OCT4 OCT4 Staining in Testicular Tumors: A Sensitive and Specific Marker for Seminoma and Embryonal Carcinoma.
Jones TD, Ulbright TM, Eble JN, Baldridge LA, Cheng L.
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN.
Am J Surg Pathol. 2004 Jul;28(7):935-40. Abstract quote
OCT4 (POU5F1) is a transcription factor expressed in embryonic stem and germ cells and is involved in the regulation and maintenance of pluripotency. It has been detected in primary testicular germ cell tumors with pluripotent potential, seminoma, and embryonal carcinoma.
We undertook immunohistochemical staining of OCT4 in a wide variety of primary testicular neoplasms (germ cell tumors and other tumors) to assess the specificity and usefulness of this marker as a diagnostic tool.
We examined histologic sections from 91 primary testicular neoplasms, including 64 cases of mixed germ cell tumors containing embryonal carcinoma (54), seminoma (51), yolk sac tumor (38), mature teratoma (31), immature teratoma (20), and choriocarcinoma (15). In addition, we examined sections from spermatocytic seminomas (5), Leydig cell tumors (8), Sertoli cell tumors (6), unclassified sex-cord stromal tumors (4), adenomatoid tumors (2), testicular tumor of adrenogenital syndrome (1), and granulosa cell tumor (1). Each tumor was examined with hematoxylin and eosin staining and with antibodies to OCT4. In all cases of mixed germ cell tumor with components of embryonal carcinoma (54) and seminoma (51), there was greater than 90% nuclear staining of the embryonal carcinoma and seminoma tumor cells with little to no background staining. In all but 1 of these cases (embryonal carcinoma), there was strong (3+) staining intensity. The other germ cell tumor components (yolk sac tumor, mature teratoma, immature teratoma, and choriocarcinoma) showed no staining.
Syncytiotrophoblast cells, which were present in 15 of the cases, were also completely negative, as were all 5 of the spermatocytic seminomas. The 22 cases of non-germ cell tumors were all immunohistochemically negative for OCT4. Fifteen of the 54 germ cell tumors containing embryonal carcinoma were also examined with antibodies to CD30. These embryonal carcinoma components were all positive for CD30 with staining of greater than 90% of the tumor cells but with variable staining intensity.
We conclude that immunostaining with antibodies to OCT4 is a useful diagnostic tool in the identification of primary testicular embryonal carcinomas and "usual," but not spermatocytic, seminomas. OCT4 immunostaining has comparable sensitivity but greater consistency compared with CD30 in the diagnosis of embryonal carcinoma.
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:
Lacking lymphoid stroma
Elevated serum hCG
The management and clinical course of testicular seminoma: 15 years' experience at a single institution.
Coleman JM, Coleman RE, Turner AR, Radstone CR, Champion AE.
Weston Park Hospital NHS Trust, Sheffield, UK.
Clin Oncol (R Coll Radiol) 1998;10(4):237-41 Abstract quote.
Testicular seminoma is one of the most curable solid neoplasms, with 5-year survival rates in excess of 90%. However, controversy persists around its optimum management, particularly for Stage I disease.
The outcome of 314 patients with testicular seminoma who were treated at a single institution is reported. A comparison of adjuvant radiotherapy and surveillance for Stage I is presented, and the possible prognostic influence of an elevated serum beta-human chorionic gonadotrophin (beta hCG) is assessed. The 5-year disease-free survival for all stages of presentation was 95.5%. There were more relapses in Stage I patients undergoing surveillance (14/94, 15%) than postorchidectomy radiotherapy (6/144, 4%; P = < 0.05). However, survival was identical irrespective of treatment policy, with no disease-related deaths in either group of Stage I patients. There were eight tumour-related deaths from advanced disease and 14 deaths from non-tumour causes. Three were due to cardiorespiratory disease, four to an unrelated second malignancy, two from infection and one from suicide; in four patients, the cause was unknown. Preoperative beta hCG was elevated in 29 (18%) of Stage I patients and in 24 (62%) of those presenting with Stage II disease. Patients were more likely to have advanced disease (> or = Stage II) if beta hCG was elevated (P < 0.001). Neither disease-free nor overall survival were influenced by the preoperative level of beta hCG.
Surveillance appears to be a safe alternative to postorchidectomy radiotherapy for Stage I disease, provided the patient is prepared for intensive long term follow-up. An increased risk of relapse, but not of tumour death, can be expected and unnecessary treatments avoided.
Prognostic factors for relapse in stage I testicular seminoma treated with surveillance.
Warde P, Gospodarowicz MK, Banerjee D, Panzarella T, Sugar L, Catton CN, Sturgeon JF, Moore M, Jewett MA.
Department of Radiation Oncology, University of Toronto and Toronto Hospital, Ontario, Canada.
J Urol 1997 May;157(5):1705-9; discussion 1709-10 Abstract quote
PURPOSE: We sought to identify prognostic factors predictive of disease progression in patients with clinical stage I seminoma on surveillance following orchiectomy.
MATERIALS AND METHODS: Between January 1981 and December 1993, 201 patients 20 to 86 years old (median age 34) with clinical stage I seminoma were placed on surveillance following orchiectomy. The potential prognostic factors studied included age, tumor size, mitotic count, S phase fraction, ploidy, presence of small vessel invasion, syncytiotrophoblasts and tumor infiltrating lymphocytes, expression of beta-human chorionic gonadotropin and low molecular weight keratin on immunohistochemistry.
RESULTS: With a median followup of 6.1 years (range 1.3 to 12.3) 31 patients had relapse for an actuarial 5-year relapse-free rate of 84.9%. The 5-year actuarial survival rate was 97.1% and the cause specific survival rate was 99.5%. On univariate analysis factors predictive of relapse were tumor size (5-year relapse-free rate 88 and 67% for tumors 6 cm. or less and greater than 6 cm., respectively, p = 0.004), age (5-year relapse-free rate 79 and 91% for age 34 years or younger versus older than 34 years, respectively, p = 0.009) and presence of small vessel invasion (5-year relapse-free rate 86 versus 69%, p = 0.01). On multivariate analysis age and tumor size were predictive of relapse, while small vessel invasion approached statistical significance. The risk of relapse in 57 patients with none of the 3 adverse prognostic factors (age greater than 34 years, tumor 6 cm. or smaller and no small vessel invasion) was 6%.
CONCLUSIONS: We identified age, size of the primary tumor and small vessel invasion as important prognostic factors for relapse in patients with stage I seminoma treated with surveillance. Further followup and assessment of biological factors are needed to optimize selection of patients at a high risk for relapse who should receive immediate postoperative therapy.
Testicular seminoma: a clinicopathologic and immunohistochemical study of 105 cases with special reference to seminomas with atypical features.
Tickoo SK, Hutchinson B, Bacik J, Mazumdar M, Motzer RJ, Bajorin DF, Bosl GJ, Reuter VE.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York.
Int J Surg Pathol 2002 Jan;10(1):23-32 Abstract quote
In spite of the high curability rates, rare cases of testicular seminoma behave in an unexpectedly aggressive manner. No effective markers are currently available that can predict such uncommon behavior.
We studied 105 cases of testicular seminoma on whom the primary resection was performed at the Memorial Sloan-Kettering Cancer Center, New York, to investigate any relationship between morphology, immunohistochemical features, and clinical/pathological stages. Fifty-nine percent of the cases presented with pT stage 1 and 74 percent with American Joint Committee on Cancer (AJCC) stage I.
In univariate analysis, tumor size, mitotic count, and presence of necrosis showed significant associations with pT stage (p = 0.0001, 0.0001, and 0.04, respectively), and the presence of vascular invasion (p = 0.0001, 0.0001, and 0.02, respectively). In multivariate analysis, both the tumor size and mitotic counts were independent predictors of pT stage (p = 0.0004 and 0.0001) and vascular invasion (p = 0.0004 and 0.0001). When tumors were separated on the basis of architectural and/or cytological atypia into 'usual seminomas' and 'seminomas with atypia,' these were significantly associated with AJCC stage (p = 0.02), and c-kit protein (p = 0.0005) and CD30 expression (p = 0.02). In addition, 'seminomas with atypia' also tended to show a higher proliferation activity as judged by Ki67 reactivity (p = 0.06), as well as express the marker of epithelial differentiation, Cam 5.2 (p = 0.09). In summary, we find that the morphologic features in testicular seminomas are associated with factors of clinical relevance. Also, 'seminomas with atypia' differ from 'usual seminomas' morphologically, present at a higher AJCC stage, and possibly represent an early step in transformation of seminomas toward a more aggressive phenotype.
While not proposing a new entity, we suggest that when these atypical features are encountered in an otherwise classical seminoma, investigations must be performed to exclude an early carcinomatous differentiation or even earlier changes toward such a differentiation, such as lack of c-kit protein expression.
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
Long-term outcome of postorchiectomy radiation therapy for stage I and II testicular seminoma.
Akimoto T, Takahashi I, Takahashi M, Yamakawa M, Hayakawa K, Mitsuhashi N, Niibe H.
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Japan
Anticancer Res 1997 Sep-Oct;17(5B):3781-5 Abstract quote
To evaluate the treatment-related late sequelae including gonadal function and second malignancy 94 patients with stage I and II testicular seminoma treated with postorchiectomy radiation therapy were analyzed retrospectively.
The 10-year cause specific, disease free and actuarial survival rates were 100, 98.5 and 96.1% for stage II and 91.7, 83.3 and 91.7% for stage II, respectively. The most common late sequelae of gastrointestinal tract was peptic ulcer, developing in 16% of all patients with a median interval of 12 months, but severity was mild except one who needed subtotal gastrectomy. Second malignancies developed in 9 patients (9.5%) with a median interval of 13 years, but calculated O/E ratio excluding 2 patients with secondary germ cell tumor of contralateral testis was 2.3 and did not reach a significant level statistically.
Concerning gonadal function assessed from the number of the children, 79% of the patients who wanted to have children after the treatment were successful in fathering children. No fatal complications were observed.
Management of stage II seminoma.
Warde P, Gospodarowicz M, Panzarella T, Catton C, Sturgeon J, Moore M, Jewett M.
Department of Radiation Oncology, Princess Margaret Hospital and the University of Toronto, Canada.
J Clin Oncol 1998 Jan;16(1):290-4 Abstract quote
PURPOSE: To assess the results of treatment, patterns of failure, and prognostic factors for relapse in a contemporary cohort of patients with stage II seminoma.
MATERIALS AND METHODS: From January 1981 and December 1993, 99 patients (median age, 35 years) with stage II seminoma (IIA, 41; IIB, 28; IIC, 24; IID, six) were managed at our institution. Eighty were treated with radiation therapy (RT) and 19 with chemotherapy (ChT).
RESULTS: With a median follow-up of 6.7 years, the five-year overall actuarial survival was 94%, the 5-year cause-specific survival was 94%, and the 5-year relapse-free rate was 83%. Sixteen (20%) of the 80 patients treated with RT relapsed (median time to relapse, 9 months). Relapse occurred outside the irradiated area in all but two patients. Distant relapse sites included the supraclavicular fossa, bone (four patients, three with spinal cord compression), and lung/mediastinum. All 19 patients treated primarily with ChT achieved disease control and none has relapsed. The relapse rate at 5 years for patients with stage IIA to IIB was 11% (seven of 64), and 56% (nine of 16) for those with stage IIC to IID disease (P < .0001). No patient with IIC or IID disease treated with ChT relapsed as compared with 56% of patients treated with RT (0 of 14 v nine of 16, P = .002).
CONCLUSION: Radiation therapy is highly effective in patients with stage IIA or IIB seminoma (89% were relapse free). In stage IIC or IID disease, although local control with RT is excellent, a 50% risk of distant relapse is unacceptable, and not all patients who relapse can be salvaged. Chemotherapy should clearly be the primary treatment in patients with stage IIC or IID seminoma.
Results of radiotherapy for 230 patients with stage I-II seminomas.
Hultenschmidt B, Budach V, Genters K, Sack H.
Department of Radiooncology, University of Essen.
Strahlenther Onkol 1996 Apr;172(4):186-92 Abstract quote
PURPOSE: The outcome of treatment of testicular seminoma in 230 patients with stage I and II disease was retrospectively evaluated in regard of survival, pattern of failure, radiation dose, treatment volume, acute and chronic side effects.
PATIENTS AND METHODS: From 1978 to 1992, 230 male patients with the diagnosis of pure seminoma of the testis were treated by postoperative radiotherapy at the University of Essen. According to the Royal Marsden Staging System, 188 patients were presenting with stage I disease, 24 with stage IIA, 13 with stage IIB and 5 with stage IIC disease. All patients received irradiation to the paraaortic lymph nodes (median dose: 36 Gy). In 154 patients the ipsilateral iliac lymph nodes were additionally irradiated with or without inguinal lymph nodes and in 66 patients the contralateral pelvic nodes were included. Since 1987, the total dose was reduced to 26 Gy for microscopic disease. A mediastinal irradiation (median dose: 30 Gy) was performed in 22 patients. Eight patients with stage IIB and IIC disease were additionally treated with chemotherapy.
RESULTS: Overall actuarial survival (Kaplan-Meier method) for all patients was 97.8% at 5 years and 96.5% at 10 years. Ten-year survival corrected for intercurrent mortality (n = 8) was 100%. In 5 patients recurrent disease (n = 5) was observed, in 6 patients seminoma occurred in the contralateral testis. For stage I seminoma the disease-free survival was 96.8%. For the whole group of stage II seminoma the DFS was 88.1%, for stage IIA 91.7% and for stage IIB 76.9%. In stage IIC no recurrences occurred. In general, the radiation therapy was well tolerated with minor side effects only.
CONCLUSIONS: Postoperative radiotherapy for seminoma stage I, IIA and IIB alone offers excellent control and survival rates with tolerable side effects.
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