Tumors

and Pilar González-Peramato²

(1)

Department of Anatomy, Histology and Neuroscience, Universidad Autónoma de Madrid, Madrid, Spain

(2)

Department of Pathology, University Hospital La Paz, Universidad Autónoma de Madrid, Madrid, Spain

Keywords

Testicular neoplasmsTesticular metastatic tumorsTesticular metastatic neuroblastomaTesticular metastatic prostate adenocarcinomaTesticular metastatic lung carcinomaTesticular metastatic urothelial carcinomaTesticular leukemia infiltration

Most of the secondary tumors of the testicle appear throughout the evolution of a well-known tumor with disseminated disease, so that its diagnosis does not present difficulties. In childhood, it is not uncommon to observe metastases of neuroblastoma, rhabdomyosarcoma, and leukemias. In the adult, testicular metastases most frequently come from primary tumors of the prostate, gastrointestinal tract, kidney, lung, melanoma, and urinary bladder.

In most cases, the histological pattern resembles that of the original tumor, but there are situations in which tumor growth raises several differential diagnoses. There are three tumors that can simulate primary testicular tumors. The carcinomas of the kidney, urinary bladder, and prostate can simulate a carcinoma of the rete testis, when they metastasize in it, or an intertubular germ cell tumor, since this type of growth is common as it also occurs with lymphomas. If the tumor cells of any carcinoma undergo cytoplasmic vacuolization, they can simulate a Sertoli cell tumor. But still more, it is estimated that a palpable testicular mass associated or not with hydrocele may be the first manifestation of a hidden tumor in nothing less than 10% of tumors. Metastases of the following tumors have been chosen as examples: adrenal neuroblastoma, acute lymphoblastic leukemia, prostate carcinoma (conventional and neuroendocrine), lung adenocarcinoma, adenocarcinoma of the colon, and urothelial carcinoma. The interest lies not only on some peculiarities of some cases but these highlight the value of immunohistochemistry in every case.

Case 126. Testicular and Spermatic Cord Metastasis from Adrenal Neuroblastoma

Clinical case. A 5-year-old boy diagnosed of neuroblastoma of the left adrenal gland with bone metastases. He developed a nodular enlargement of the left testicle and the spermatic cord that required radical orchiectomy.

Pathological findings. The presence of several tumor nodules along the spermatic cord is observed in the longitudinal section of the surgical specimen, affecting the epididymis and the testicle. Most of the tumor is located inside the vessels. However, areas of tumor infiltration are observed both at the level of the spermatic cord, in the epididymis and in the periphery of the testicle. The tumor cells are small; they show a tendency to form pseudorosettes and have a high mitotic index. Immunohistochemically, the tumor cells show immunoexpression for both chromogranin and synaptophysin.

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Longitudinal section of the testicle, the epididymis, and the spermatic cord. Multiple tumor nodules in the testicle, the head of the epididymis, and along the spermatic cord following the vessels

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Cross section of the spermatic cord in which vas deferens is recognized showing a well-defined tumor that reaches its vicinity and clusters of tumor cells inside a vessel

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Tumor cells are observed inside the vessels and in the connective tissue of the tunica vasculosa, focally infiltrating the parenchyma

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The cells are arranged in sheets; they have spherical or ovoid nuclei and scarce cytoplasm. They have a tendency to form pseudorosettes

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Part of the nucleus of a tumor cell and its cytoplasm, as well as prolongations of the cytoplasm of neighboring cells. All of them contain small electrodense granules surrounded by a membrane (electron microscopy)

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Immunoexpression for chromogranin in the cytoplasm of tumor cells

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Strong immunoexpression for synaptophysin in the tumor cells

Comments. Involvement of the testicle and paratesticular structures in neuroblastoma is not frequent; however, it is the childhood tumor that metastasizes in the testicle more frequently. Paratesticular is more frequent than testicular involvement. In most cases, these patients have an advanced infradiaphragmatic disease. Although testicular involvement may manifest as a primary tumor several years after a successful treatment of neuroblastoma, it is considered a recurrence. The most plausible route is retrograde lymphatic dissemination from the abdominal mass. In this case, the retrograde venous route seems to be the most probable one. The potential origin of some paratesticular neuroblastomas is speculated to be the paratesticular sympathic remnants.

References

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Köseoğlu V, Akata D, Kutluk T, Yalçin B, Arat A, Sökmensüer C, Büyükpamukçu M. Neuroblastoma with spermatic cord metastasis in a child: sonographic findings. J Clin Ultrasound. 1999;27:287–9.
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Case 127. Testicular Relapse in Acute Lymphoblastic Leukemia

Clinical case. A 13-year-old patient diagnosed with lymphoblastic leukemia with remission. After several years, the testicular recurrence is confirmed by testicular fine needle aspiration. Orchiectomy and biopsy of the contralateral testicle was performed.

Pathological findings. The testicle measures 3.5 × 3 × 3 cm. The sectioned surface is whitish-gray, homogeneous, and bright. A hemorrhagic area can be observed in the path of the puncture needle. The infiltrate by leukemic cells is preferably diffuse and separates the seminiferous tubules, and in some fields it has a perivascular or peritubular arrangement. The lymphoid cells infiltrate the tunica albuginea, dissecting the collagen bundles and arranging themselves in a single line. They also infiltrate the testicular mediastinum respecting the channels of the rete testis. The tumor cells express TDT and CD79a. The proliferation index estimated with Ki67 is very high. The seminiferous tubules had a germ cell maturation delay with Sertoli cells of spherical nuclei and small nucleolus. Spermatogonia, rare, only occasionally gives rise to isolated spermatocytes. The biopsy of the contralateral testis shows the same maturation stage of the parenchyma but did not present with leukemic infiltrates.

../images/471462_1_En_10_Chapter/471462_1_En_10_Figh_HTML.jpg — Fig. 1

Longitudinal section of the testicle. The testicle shows a whitish-gray and shiny homogeneous surface due to complete infiltration of the parenchyma

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The interstitium is enlarged by a diffuse infiltration that separates the seminiferous tubules

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The albuginea shows a great thickening. The tumor cells are arranged in planes parallel to the surface between the layers of fibroblasts

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Infiltration of the testicular mediastinum. In the central part, several cavities of the rete testis with cubic epithelium are observed

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Small cell infiltrates, hyperchromatic nucleus with several mitoses between sections of two seminiferous tubules, showing the absence of lumen, immature Sertoli cells and isolated spermatogonia

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Clusters of leukemic cells surrounding small vessels of the testicular interstitium

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Intense immunoexpression for TDT in all tumor cells

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Strong immunostaining for CD79a of lymphoid cells

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The cell proliferation index of the tumor cells is very high (Ki67)

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The seminiferous tubules immersed in the lymphoid infiltrates preserve the immunoexpression for inhibin in Sertoli cells

Comments. Relapse in patients with acute lymphoblastic leukemia affects usually the bone marrow. Testicular involvement, along with the brain, are signs of poor prognosis. The testicle is affected in less than 1% of cases. Testicular relapses have been suggested to be due to the presence of a cell clone different from the one that produces relapse in the bone marrow and that would be immune to chemotherapy treatment.

References

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Arima K, Hasegawa D, Ogawa C, Kato I, Imamura T, Takusagawa A, Takahashi H, Kitagawa Y, Hori T, Tsurusawa M, Manabe A, Hosoya R. Detection of submicroscopic disease in the bone marrow and unaffected testis of a child with T-cell acute lymphoblastic leukemia who experienced “isolated” testicular relapse. Int J Hematol. 2009;90:370–3.
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Ding LW, Sun QY, Mayakonda A, Tan KT, Chien W, Lin DC, Jiang YY, Xu L, Garg M, Lao ZT, Lill M, Yang H, Yeoh AE, Koeffler HP. Mutational profiling of acute lymphoblastic leukemia with testicular relapse. J Hematol Oncol. 2017;10:65.
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Barredo JC, Hastings C, Lu X, Devidas M, Chen Y, Armstrong D, Winick N, Wood BL, Yanofsky R, Loh M, Gastier-Foster JM, Jorstad DT, Marcus R, Ritchey K, Carrol WL, Hunger SP. Isolated late testicular relapse of B-cell acute lymphoblastic leukemia treated with intensive systemic chemotherapy and response-based testicular radiation: a Children’s Oncology Group study. Pediatr Blood Cancer. 2018;65(5):e26928.
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Gabelli M, Zecca M, Messina C, Carraro E, Buldini B, Rovelli AM, Fagioli F, Bertaina A, Lanino E, Favre C, Rabusin M, Prete A, Ripaldi M, Barberi W, Porta F, Caniglia M, Santarone S, D’Angelo P, Basso G, Locatelli F. Hematopoietic stem cell transplantation for isolated extramedullary relapse of acute lymphoblastic leukemia in children. Bone Marrow Transplant. 2019;54:275–83.
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Gaudichon J, Jakobczyk H, Debaize L, Cousin E, Galibert MD, Troadec MB, Gandemer V. Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues. Blood Rev. 2019;36:40–56.

Case 128. Infiltration by Chronic Lymphatic Leukemia (CLL): Fungus Testis

Clinical case. A patient with CLL with no current treatment by his own decision. Four weeks earlier, he had a feverish peak associated with edema and scrotal swelling. He was diagnosed a right orchidoepididymitis and administered antibiotics. His evolution is poor, so a testicular abscess was suspected and scrotal spontaneous suppuration was observed. The ultrasound showed an increase of his right testicle volume, of heterogeneous echogenicity, a moderate decrease in vascularization that associated important inflammatory changes in the epididymis and the ipsilateral covers. As a first possibility, these findings were suggestive of right orchiepididymitis in evolution but without being able to rule out an underlying tumor pathology. Testicular microcalcifications were also observed. No collections suggestive of abscesses or hydrocele were identified.

Pathological findings. An orchiectomy specimen that includes soft parts and a scrotal sinus, measuring 7 × 5 × 3.5 cm and weighing 79 g. The sectioned surface shows a slight thickening of the epididymis and the spermatic cord. The testicle is replaced by an extensive necrosis in continuity with the external side of the specimen. Histologically,there are large clusters of lymphoid cells at the level of the epididymis and the spermatic cord, most of them similar to adult lymphocytes. The most affected part of the epididymis is the head. The lymphoid infiltrates surround all the efferent ducts. In both the epididymis and the spermatic cord, the infiltrates are also located around the vessels, inside them, and between the fat cells. In the testicle, there is extensive necrosis. At this level, the nature of the infiltrates varies from one area to another. There are collections of polynuclear, macrophage clusters with extensive eosinophilic and granular cytoplasms and plasma cell clusters. The few non-necrotic seminiferous tubules are atrophic and appear surrounded by leukemic cells. The immunohistochemical study of the lymphocytic infiltrates shows a profile compatible with the untreated CLL: most of the cells are positive for CD79a, CD20, CD5, and CD23.