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FDA approves another trastuzumab biosimilar for HER2-positive breast cancer, gastric cancer
The Food and Drug Administration has approved Trazimera (trastuzumab-qyyp), a biosimilar of ...
Laura Alder is a Resident in Internal Medicine, Taha Al-Juhaishi is a Fellow in Hematology and Oncology, both at Virginia Commonwealth University and Hunter Holmes McGuire VA Medical Center in Richmond, Virginia. Steven Smith is an Associate Professor, Department of Pathology; and Asit Paul is an Associate Professor, Division of Hematology, Oncology and Palliative Care, Department of Internal Medicine; both at Virginia Commonwealth University in Richmond.
Correspondence: Asit Paul (asit.paul@ vcuhealth.org)
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
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Our report shows a rare occurrence of a testicular swelling as an initial presentation of an aggressive metastatic gastric adenocarcinoma. When a patient presents with a testicular swelling, a testicular neoplasm is suspected based on the clinical examination, serum tumor markers, and ultrasonographic examination of the testes. Inguinal orchiectomy is the initial standard of care, and pathologic examination of a resected testis renders the confirmatory diagnosis. The overwhelming majority of these patients have primary testicular neoplasms, predominantly testicular germ-cell tumors. A small group may have atypical and rare tumors requiring additional workup to establish a diagnosis.
Metastatic spread of a solid tumor to a testicular site is rare. A testis is somewhat protected by the distinct anatomy that is offered by the blood-testis barrier. The tunica vaginalis, an external fibrous covering sheath of the testis, separates the testis from the peritoneal cavity and provides additional protection. Nevertheless, possible routes of secondary metastatic spread may include hematogenous and lymphovascular spread, cavitary dissemination and peritoneal seeding. Among gastric cancers, diffuse gastric cancer subtype is commonly associated with signet-ring cells. These cells lack adhesion and invade as single cells or small groups, leading to scattered tumor cells and a higher probability of seeding.
Our patient exhibited extensive peritoneal carcinomatosis, so peritoneal seeding likely played a dominant role in disseminating the cancer to the testis. It should be noted that possible primary sites of signet-ring cell metastatic adenocarcinomas are broad and may include the stomach and other GI and pancreaticobiliary sites, as well as the lung, bladder, breast, and gynecologic tract. Immunohistochemistry is often of limited value in establishing the primary site. Diagnosis is best established on clinical grounds, as was done in our patient.
When signet-ring cells are encountered in an orchiectomy specimen and a primary extratesticular site of origin cannot be identified, it is important to consider rare variants of primary testicular tumors in the differential diagnosis. A number of primary testicular tumors have signetring morphology. These include primary signetring cell stromal tumor of the testis (PSRST), 12 seminoma with signet-ring cell predominance, 13 and a primary signet-ring cell germ-cell carcinoma of the testes (PSRGCT). 14
Seminoma and PSRST variants generally are differentiated from adenocarcinoma by a lack of mucin production and the absence of keratin expression. PSRGCT is considered a
malignant somatic-type transformation of a testicular germ-cell tumor and germ-cell clonality is established by abnormal 12p chromosome through fluorescent in situ hybridization testing. 13 PSRST is a benign tumor with excellent prognosis. Seminoma variants with signet-ring cell predominance and PSRGCT are managed as germ-cell tumors and are also considered to have good outcome. In contrast, testicular involvements from metastatic adenocarcinomas, including gastric cancers, are managed with multidisciplinary approach, including systemic chemotherapy. Despite this, patients have a poor outcome with a median survival of about 1 year. 2
Advanced gastric adenocarcinoma can metastasize to the testes, and patients may present with a testicular swelling as an initial presentation. It is important to differentiate secondary testicular cancers from rare variants of primary testicular tumors because the prognosis and management vary substantially.
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