Paratesticular paraganglioma: a rare cause of an intrascrotal mass.
Abstract: We describe a case of a paratesticular paraganglioma in a 33-year-old man who presented with a scrotal mass and underwent a right testicular exploration. Metastasis is the only definite criterion for diagnosis of a malignant paraganglioma; however, lymphovascular invasion was noted in this case, which warranted a close clinical surveillance.The patient is currently well with no evidence of disease 18 months after radical orchiectomy. Paratesticular paragangliomas are extremely rare tumors with 6 cases reported in English literature. The histogenesis of these tumors is unknown. Though the histology and immunohistochemistry resemble those of paragangliomas at any other location, these tumors raise a plethora of differential diagnoses especially with the more commonly occurring tumors. Herein the relevant histopathologic differential diagnoses are discussed along with a brief review of literature.

(Arch Pathol Lab Med. 2009;133:811-813)
Article Type: Case study
Subject: Testicular cancer (Diagnosis)
Testicular cancer (Causes of)
Testicular cancer (Case studies)
Testicular cancer (Prognosis)
Authors: Gupta, Ruta
Howell, R. Spencer
Amin, Mahul B.
Pub Date: 05/01/2009
Publication: Name: Archives of Pathology & Laboratory Medicine Publisher: College of American Pathologists Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2009 College of American Pathologists ISSN: 1543-2165
Issue: Date: May, 2009 Source Volume: 133 Source Issue: 5
Accession Number: 230152006
Full Text: Extra-adrenal paragangliomas are neoplasms arising from cells of neural crest origin anywhere along the distribution of the sympathoadrenal neuroendocrine system. Nearly 85% are intra-abdominal, 12% are intrathoracic, and 3% are cervical. (1) Some of the unusual sites for paragangliomas include the kidney, urethra, urinary bladder, prostate, spermatic cord, gallbladder, uterus, and vagina. (1) Paratesticular paragangliomas are extremely rare with only 6 cases in the spermatic cord reported in English literature to date. (2-7)

Herein a case of a primary paratesticular paraganglioma in a 33-year-old man is described. The relevant differential diagnoses and probable histogenesis are discussed.

REPORT OF A CASE

The patient, a 33-year-old, otherwise healthy man presented at another institution with a long-standing dragging pain in the scrotum. On physical examination, a palpable mass was noted near the upper pole of the right testis. Ultrasonography revealed an isoechoic mass near the epididymis of the right testis. The patient did not complain of headaches or diarrhea, he did not have hypertension, and all the biochemical markers and serum tumor markers were within normal limits. A surgical exploration and right orchiectomy was performed.

On gross examination, a 5.5 X 4 cm mass was noted near the epididymis, the cut surface of which had a multilobulated, fleshy appearance with occasional hemorrhagic and cystic areas. The right testis and the spermatic cord were normal in size and unremarkable in appearance.

Multiple formalin-fixed and routinely processed sections from the neoplasm were stained with hematoxylin-eosin for light microscopy. Histopathologic examination revealed a nodular expansile mass in the epididymis with occasional cystic areas and hemorrhage (Figure 1, A). The cells were arranged in nests separated by fibrovascular septa, reminiscent of zell ballen arrangement (Figure 1, B). Individual cells were polygonal with a granular eosinophilic cytoplasm and central nucleus. The nuclei had few small nucleoli with open to stippled chromatin (Figure 1, C). A single focus of lymphovascular invasion was noted. Mitotic activity was rare and one mitotic figure was counted in 50 high-power fields. Necrosis was absent. The testicular parenchyma was unremarkable and did not show tumor extension or intratubular germ cell neoplasia.

The epithelioid-appearing neoplasm with prominent sinusoidal vasculature and nested architecture was then referred to Cedars Sinai Medical Center for a definitive diagnosis. The differential diagnoses included a paraganglioma, adenomatoid tumor, malignant mesothelioma, paratesticular leydig cell tumor, carcinoma of the rete testis, a melanotic neuroectodermal tumor, and a desmoplastic small round cell tumor. Origin or a definitive involvement of the tunica vaginalis or the rete testis could not be demonstrated after correlation of gross and microscopic findings.

Immunohistochemical studies were carried out using the streptavidin-biotin method for antibodies to synaptophysin, chromogranin, S100 protein, CD56, WT1, desmin, cytokeratin, HMB-45, calretinin, placental alkaline phosphatase, inhibin, carcinoembryonic antigen (CEA) and CD99. The tumor cells showed a patchy but distinct immunoreactivity to synaptophysin (Figure 2, A) and chromogranin and strong diffuse cytoplasmic membrane immunoreactivity to CD56 (Figure 2, B); immunoreactivity to S100 protein highlighted the sustentacular pattern. The tumor cells were nonimmunoreactive to all the other immunostains. The case was thus interpreted as a paraganglioma, and in view of the unusual location it was thought essential to rule out metastasis.

Postoperative computed tomographic imaging of the patient's abdomen, retroperitoneum, chest, and neck did not reveal any abnormality. The patient was asymptomatic and the results of his blood chemistries were within normal limits. Also, after nearly 18 months of follow-up, the patient does not have any other lesion or mass.

Thus a diagnosis of a primary paratesticular paraganglioma was made. The presence of lymphovascular emboli prompted regular clinical surveillance.

Currently, 18 months after the initial surgery the patient is healthy with no residual disease or metastasis.

[FIGURE 1 OMITTED]

COMMENT

Paragangliomas may occasionally occur at unusual sites such as the thyroid, lung, gallbladder, duodenum, urinary bladder, and the uterus. (1) The paratestis is a rare site with only 6 cases of paraganglioma of the spermatic cord documented in the literature. While paraganglia can occasionally line various areas of urogenital tract such as the bladder and the prostate, to our knowledge none have been described in the paratesticular region. (1) The histogenesis of paraganglioma of the spermatic cord is an enigma, though it has been speculated that paraganglionic nests in the spermatic cord may be secondary to dysgenesis during embryogenesis. (2,6)

[FIGURE 2 OMITTED]

Histologically paraganglia in the paratestis are indistinguishable from paraganglia found at other sites. However, in this unusual location several other common benign and malignant entities need to be ruled out. Absence of gland-like spaces and tubule and cord formation with nonreactivity to keratin, WT1, and calretinin precluded the diagnosis of a benign adenomatoid tumor. Normal tunica vaginalis, an expansile lesion without infiltrative growth, and nonreactivity to WT1, CEA, and calretinin ruled out a mesothelioma. Melanotic neuroectodermal tumors are rare in the paratestis and occur in infants; these also show 2 cell populations and express HMB-45. Thus, based on the zell ballen architectural pattern with strong immunoreactivity to CD56 and synaptophysin with sustentacular cell pattern of immunoreactivity to S100 protein confirmed the diagnosis of a paratesticular paraganglioma.

Paragangliomas at any location in the body generally have a favorable prognosis. Mitotic activity, necrosis, and lymphovascular emboli have been cited as some of the unfavorable prognostic factors. Though these features have been studied in bladder paragangliomas, none of them were found to be reliable. (8) The only consistent criterion for malignancy in paraganglioma at any site is metastasis. (1) In this particular case lymphovascular emboli were evident, necessitating a close clinical surveillance. A similar finding has not been documented in the 6 previously reported cases of paragangliomas nor have lymphovascular emboli been discussed as independent prognostic factors. (2-8)

In summary, it is essential to be aware that paragangliomas may arise from the embryonic chromaffin cells that may have accompanied the testis; nevertheless, it is important to rule out a metastasis from other sites. (1,2) Presence of lymhovascular emboli raise several questions regarding the malignant potential of the tumor and warrant a close follow-up of the patient.

Accepted for publication August 19, 2008.

References

(1.) Extra adrenal paragangliomas of the sympathoadrenal neuroendocrine system. In: Lack EE, ed. Atlas of Tumor Pathology, Tumors of the Adrenal Gland and Extra Adrenal Paraganglia. 3rd ed. Bethesda, Md: Armed Forces Institute of Pathology; 1997:269-284.

(2.) Eusebi V, Massarelli G. Phaeochromocytoma of the spermatic cord: report of a case. J Pathol. 1971;105:283-284.

(3.) Soejima H, Ogawa O, Nomura Y, Ogata J. Pheochromocytoma of the spermatic cord: a case report. J Urol. 1977;1 18:495-496.

(4.) Bacchi CE, Schmidt RA, BrandAlo M, Scapulatempo R, Costa JC, Schmitt FC. Paraganglioma of the spermatic cord. Report of a case with immunohistochemical and ultrastructural studies. Arch Pathol Lab Med. 1990;1 14:899-901.

(5.) Dharkar D, Kraft JR. Paraganglioma of the spermatic cord. An incidental finding. J Urol Pathol. 1994;2:89-93.

(6.) Attaran SY, Shakeri S, Sobhani AR. Paraganglioma of the spermatic cord: report of a case. J Urol. 1996;1 55:651.

(7.) Young IE, Nawroz IM, Aitken RJ. Phaeochromocytoma of the spermatic cord. J Clin Pathol. 1999;52:305-306.

(8.) Cheng L, Leibovich BC, Cheville JC, et al. Paraganglioma of the urinary bladder: can biologic potential be predicted? Cancer. 2000;88:844-852.

Ruta Gupta, MD; R. Spencer Howell, MD; Mahul B. Amin, MD

From the Department of Pathology Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif (Drs Gupta and Amin); and Mercy Hospital, Miami, Fla (Dr Howell).

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Mahul B. Amin, MD, Department of Pathology and Laboratory Medicine, Cedars Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048 (e-mail: aminm@cshs.org).
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