Testicular Cancer: An Unlikely Etiology for Iron Deficiency Anemia

Case Report

A 34-year-old Hispanic man without any prior medical history presented to the emergency room complaining of dizziness with exertion for 2 weeks. He denied any shortness of breath, fever, abdominal pain, or melena, but did note a 5-pound weight loss, poor appetite, and night sweats. At the emergency room he was afebrile, tachycardic to 122, and normotensive without orthostatic changes.

His physical examination was significant for pale conjunctivae, and tachycardia, but otherwise was unremarkable. Significant laboratory values included: Hgb 5.3, MCV 67.5, RDW 20.5, iron level 11 (nl 40190), TIBC 330 (nl 250-400), transferrin 258 (nl 188341), ferritin 7 (nl 30-330), normal chest x-ray, and negative fecal occult blood. Peripheral smear showed microcytosis with cigar cells and nucleated red blood cells. Further studies revealed normal expression of CD 55 & 59, and normal coagulation studies and DIC panel (see Table 1).

CT imaging revealed a 7.4 cm segment of irregular thickening and enhancement of the third and fourth portion of the duodenum without luminal obstruction, as well as a 3.2 cm retroperitoneal lymph node (see Figure 1). Upper endoscopy revealed a multilobulated friable mass of the duodenum which was biopsied and initially interpreted as adenocarcinoma (see Figure 2). Upon subsequent physical examination, his right testicle had a vague fullness. Therefore, a testicular ultrasound was performed and revealed non-specific hypoechogenicities of the right testicle. Tumor markers were subsequently ordered and returned elevated: AFP 1210 (nl 0-2) and tumor HCG 9045 (nl <2). Given these findings and concern for a potential midline metastasis from a testicular cancer, we asked the pathology service to re-examine the duodenal biopsy. Special stains obtained on the duodenal biopsy were positive for CD30, AFP, and HCG. Upon repeat review by several pathologists, the biopsy was subsequently interpreted as metastatic embryonal carcinoma (see Figure 3). The patient then underwent a right orchiectomy, which closely resembled the histology of the duodenal biopsy (see Figure 4). He was immediately started on bleomycin, etoposide and cisplatin and his tumor markers have decreased to normal after several cycles of chemotherapy. He subsequently underwent resection of the residual retroperitoneal mass after chemotherapy and is in remission.

Figure 1. CT of the abdomen and pelvis revealed a 7.4 cm segment of irregular thickening and enhancement of the third and fourth portion of the duodenum without obstruction of the lumen, as well as a 3.2 cm retroperitoneal lymph node.

Figure 2:(Panel A) Friable mass in the 3rd and 4th portion of the duodenum on endogastroduodenoscopy with subsequent biopsy (Panel B) initial read as infiltrative moderately differentiated adenocarcinoma. Reexamination of pathology upon clinical suspicion of testicular cancer reveals stain positive for CD 30+, AFP+, scanty foci HCG+, consistent with embryonal carcinoma.

Figure 3: Testicular ultrasound showing area of bright echos in the right testis and area of hypoechoic area in the right testicular parenchyma with small hydrocele right greater than left, suspi-cious for testicular neoplasm.

Midline lesions are a common site of testicular cancer metastasis. The diagnosis of testicular cancer in midline lesions may be difficult to diagnose in the absence of clinical suspicion. In the case of a small intestinal tumor, one must consider the possibilities of carcinoid tumor, GIST (gastric intestinal stromal tumor), leiomyosarcoma, gastric lymphoma, gastric adenocarcinoma, and metastatic disease. A biopsy would best be able to differentiate between the various possibilities. However, the histological features of certain germ cell tumors may be undiffentiated, such as that of embryonal carcinoma, which shows undifferentiated totipotential cells, and thus the true diagnosis may be obscured. In our case, where testicular cancer was suspected, re-examination of the pathology of the duodenum with immunohistochemistry (CD30, HCG, and AFP) was helpful in making the diagnosis. In the setting of midline lesions having unclassifiable features, we recommend further special stains and molecular or cytogenetic studies to establish diagnosis. The presence of i(12p) chromosomal marker (increased 12p copy number, or a deletion of the long arm of chromosome 12), which is the genetic marker for testicular cancer, has been associated with response to cisplatin based chemotherapy⁹. This suggests that a number of midline lesions of unknown primary may be germ cell cancer in origin.

Management of metastatic germ cell tumors depends on the classification of the disease developed by The International Germ Cell Cancer Collaboration Group (IGCCG)¹⁰. In this stratification system, patients are separated into good, intermediate, and poor-prognostic groups according to predicted outcome to cisplatin-combination chemotherapy, based on histology, site of metastasis, serum tumor marker elevation, and primary site of tumor. With treatment, good prognostic disease has a 5-year progression-free rate of 88% with an overall survival of 91% ¹⁰. The standard therapy for patients in this group is either 4 cycles of EP (etoposide and cisplatin) or 3 cycles of BEP (bleomycin, etoposide, and cisplatin)¹¹. The 5year progression-free rate and survival rate is lower for intermediate and poor-prognostic disease with 75%/80% and 41%/48%, respectively. The standard therapy for patients with intermediate to advanced disease is 4 cycles of BEP. Attempts to improve this regimen, including intensifying BEP regimen, substituting ifosfamide for bleomycin, incorporating high-dose chemotherapy with autologous stem-cell support, have not demonstrated advantage over the standard regimen of 4 cycles of BEP^12-14. Post-chemotherapy resection of residual mass in patients whose tumor markers have normalized have been shown to be important in patients with nonseminoma as the incidence of viable germ cell tumors is as high as 5% to 20% in residual tumors^15,16.

In conclusion, it is important to recognize that metastatic testicular tumors most often metastasize to midline lesions and may present as iron-deficiency anemia and gastrointestinal bleeding in the absence of a palpable testicular mass. In a young man who presents gastrointestinal bleeding, metastatic germ cell tumor should be considered in the differential diagnosis.

Figure 4: The pathology of right testicular mass upon right orchiectomy showing embryonal carcinoma focus with intratubular germ cell neoplasia measuring 1.7 cm by 0.6 cm. Panel A is a lower magnification showing calcification surround tumor and panel B is a higher magnification view.