Protocol for the Examination of Specimens From Patients With Malignant Germ Cell and Sex Cord–Stromal Tumors of the Testis, Exclusive of Paratesticular Malignancies

This protocol is intended to assist pathologists in providing clinically useful and relevant information as a result of the examination of surgical specimens. Use of this protocol is intended to be entirely voluntary. If equally valid protocols or similar documents are applicable, the pathologist is, of course, free to follow those authorities. Indeed, the ultimate judgment regarding the propriety of any specific procedure must be made by the physician in light of the individual circumstances presented by a specific patient or specimen.It should be understood that adherence to this protocol will not guarantee a successful result. Nevertheless, pathologists are urged to familiarize themselves with this document. Should a physician choose to deviate from the protocol owing to the circumstances of a particular patient or specimen, the physician is advised to make a contemporaneous written notation of the reason for the procedure followed.The College recognizes that this document may be used by hospitals, attorneys, managed care organizations, insurance carriers, and other payers. However, the document was developed solely as a tool to assist pathologists in the diagnostic process by providing information that reflects the state of relevant medical knowledge at the time the protocol was first published. It was not developed for credentialing, litigation, or reimbursement purposes. The College cautions that any uses of the protocol for these purposes involve considerations that are beyond the scope of this document.The protocol emphasizes the importance of relevant clinical information in the pathologic evaluation of specimens. Serum marker studies play a key role in the clinical management of patients with testicular germ cell tumors.1–3 The occurrence of elevated serum levels of α-fetoprotein or the β subunit of human chorionic gonadotropin may indicate the need for additional sections of certain specimens if the initial findings do not account for such elevations. As another example, gynecomastia accompanies tumors in the sex cord–stromal category more frequently than germ cell tumors,45 and an awareness of this clinical finding alerts the pathologist to consider the possibility of a sex cord–stromal tumor.The protocol applies to malignant tumors of the testis, the vast majority of which are of germ cell origin. It may also be applied to other malignant or potentially malignant tumors of the testis included in the following World Health Organization classification.4–15 For lymphomas and plasmacytomas of the testis, refer to the non-Hodgkin's lymphoma protocol.The protocol recommends staging according to the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) TNM Staging System.16 Additional criteria for staging seminomas according to a modification of the Royal Marsden system are also recommended.17 Some studies suggest that the staging of disease in patients with seminoma by the TNM system is less meaningful therapeutically than staging by a modification of the Royal Marsden method.1617 The latter staging system subdivides cases with retroperitoneal metastases into several groups according to the total tumor dimension rather than the size of the largest lymph node, as in the TNM system. Also, the data from a large Danish study of seminomas clinically limited to the testis do not support the conclusion that local staging of the primary tumor, as performed in the TNM system, provides useful prognostic information; rather, the most valuable prognostic indicator was the size of the seminoma.18 This protocol therefore encourages the use of both the TNM system and the modified Royal Marsden staging system for patients with seminoma.* By AJCC/UICC convention, the designation “T” of the TNM classification refers exclusively to the first resection of a primary tumor. The prefix symbol “p” refers to the pathologic classification of the TNM (pTNM), as opposed to the clinical classification. Pathologic classification is based on gross and microscopic examination. Therefore, pT entails a resection of the primary tumor or biopsy adequate to evaluate the highest pT category; pN entails removal of nodes adequate to validate lymph node metastasis; and pM implies microscopic examination of distant lesions. Clinical classification (cTNM) is usually carried out by the referring physician before treatment during initial evaluation of the patient or when pathologic classification is not possible.The absence or presence of residual tumor following preoperative, nonsurgical therapy (eg, chemotherapy or radiation treatment) may be described by the symbol “R” and is classified as follows:If residual tumor is present, its extent may be documented by the TNM classification preceded by the symbol “y” (eg, ypT1). Local recurrence following a previous resection should be classified with the prefix “r” (eg, rpT1).Regional Lymph Nodes (N)Distant Metastasis (M)Serum Tumor Markers (S)Stage GroupingsModified Royal Marsden Staging System17In several studies, the presence of vascular space invasion (usually lymphatic, but possibly also capillary or venous invasion) has been correlated with a significantly elevated risk for distant metastasis.19–25 This observation, therefore, is most pertinent for patients who have clinical stage I disease, that is, those who have no evidence of spread beyond the testis by clinical examination (including radiographic and serum marker studies). Some clinicians treat patients who have clinical stage I disease and whose testicular germ cell tumors lack evidence of lymphatic or vascular invasion (and possibly have other favorable prognostic features such as relatively small amounts of embryonal carcinoma) by close follow-up examinations rather than intervention. This practice is currently more accepted for patients who have tumors with 1 or more nonseminomatous components than it is for patients with pure seminoma.Important findings include Leydig cell hyperplasia, which may be correlated with β-human chorionic gonadotropin elevation; scarring, the presence of hemosiderin-laden macrophages, and intratubular calcification, which may indicate regression of a tumor; testicular atrophy; and abnormal testicular development (eg, dysgenesis or androgen-insensitivity syndrome).2627The entire testicular tumor may be blocked if it requires 10 blocks or fewer (tissue may be retained for special studies); 10 blocks of larger tumors may be taken unless the tumor is >10 cm, in which case 1 block may be submitted for every 1 cm of maximum tumor dimension. Some blocks should contain the interface with nontumorous testis because lymphatic invasion is best appreciated there. Tissues to be sampled include all of the grossly different types of tumor; testicular hilus; uninvolved testis; spermatic cord, including cord margin; epididymis; other lesion(s); all identifiable lymph nodes*; and other tissue(s) submitted with the specimen.* For large masses that have obliterated individual nodes, 1 section for every centimeter of maximum tumor dimension, especially fleshy-appearing foci, may be taken.The role of cytologic diagnosis in patients with testicular tumors is ordinarily limited to the investigation of possible metastatic lesions, usually by fine-needle aspiration. The cytologic investigation by fine-needle aspiration of the primary testicular neoplasm is unnecessary because orchiectomy must be performed for proper classification and treatment. Furthermore, the cytologic diagnosis is often incomplete owing to sampling limitations and the frequently heterogeneous nature of testicular tumors.Often the most important distinction in patients with metastatic testicular germ cell tumor, particularly following initial chemotherapy, is the differentiation of metastatic teratoma from nonteratomatous types of germ cell tumor. Pure teratomatous metastasis is generally treated by surgical excision, whereas patients who have metastatic embryonal carcinoma, yolk sac tumor, etc, are usually treated with chemotherapy. For cytologic diagnosis, specify seminoma versus nonseminomatous germ cell tumor, and teratomatous versus nonteratomatous germ cell tumor, if possible. Illustrative diagnoses are as follows: (1) positive for malignant cells from a nonseminomatous germ cell tumor, consistent with metastatic embryonal carcinoma; (2) positive for malignant cells from a nonseminomatous germ cell tumor, consistent with metastatic teratoma; (3) positive for malignant cells from a nonseminomatous germ cell tumor, further classification not possible; and (4) positive for malignant cells, consistent with metastatic germ cell tumor, further classification not possible.Contributors: the College of American Pathologists Cancer Committee; Richard S. Foster, MD; Patrick J. Loehrer, MD; Judd W. Moul, MD; Jae Y. Ro, MD; Robert E. Scully, MD; and Gillian M. Thomas, MD.