Pathologic Quiz Case: A 33-Year-Old Man With an Abdominal Mass

A 33-year-old African-American man presented with a 3-week history of back pain, shortness of breath, cough, fevers, and vomiting. He had experienced a 20-lb weight loss and complained of constipation for 4 days prior to admission. His past medical history was significant for an upper gastrointestinal bleed secondary to a duodenal ulcer 4 weeks prior to admission. He was hypertensive and carried the sickle cell trait. He had a 16-pack-year smoking history and drank a 6-pack of beer a day. On admission, his vital signs were stable. He was in mild distress and had a distended abdomen with no palpable organomegaly. Coarse breath sounds were heard over the right lower chest, and that area was also dull to percussion.A computed tomographic scan showed bilateral pleural effusions (greater on the right side), a 2.5-cm left lower lobe lung nodule, multiple low-density liver lesions, multiple retroperitoneal nodules with involvement of the right kidney with hydronephrosis, a large inferior vena cava thrombus, and evidence of small bowel obstruction. Laboratory values were significant for a white blood cell count of 26.4 × 109/L with 0.93 neutrophils, 0.03 lymphocytes, and 0.03 monocytes; a platelet count of 939 × 109/L; serum urea nitrogen, 6.8 mmol/L; and creatinine, 115 μmol/L. Urinalysis showed trace protein and rare white cells but no blood. The patient was started on heparin, and a percutaneous, ultrasound-guided needle core biopsy of the retroperitoneal mass was performed.Touch imprints from the needle core biopsy showed clusters of large malignant cells with well-defined cytoplasmic borders, hyperchromatic nuclei, slightly irregular nuclear contours, and prominent nucleoli (Figure 1). A subsequent pleural fluid specimen showed malignant cells with similar cytologic features. The biopsy showed sheets and cords of large epithelioid cells with abundant eosinophilic cytoplasm and enlarged hyperchromatic nuclei with conspicuous nucleoli (Figure 2, A, low power, original magnification ×25; B, high power, original magnification ×100). There was a small amount of intervening stroma with neutrophils. Areas of necrosis were present. The tumor cells were positive for keratins (CAM 5.2, AE1/AE3) and vimentin, but negative for S100 protein and lymphoid markers (leukocyte common antigen, CD20) by immunohistochemical staining. Transmission electron microscopy demonstrated large tumor cells with irregular nuclei, streaming bundles of cytokeratin, and varying amounts of rough endoplasmic reticulum, mitochondria, and lysosomes (Figure 3). No intercellular junctions were seen. No glandular or endocrine features were identified.What is your diagnosis?Renal medullary carcinoma (RMC) was first described as an entity by Davis et al at the Armed Forces Institute of Pathology, Washington, DC, who called it the “seventh sickle cell nephropathy.” 1 It is a highly aggressive neoplasm that is strongly associated with the sickle cell trait. Following the original description of 34 cases1, with radiologic2 and clinical findings,3 a small number of case reports have been reported in the English language literature.In the original report of Davis et al,1 the patients ranged in age from 11 to 39 years. Nine patients had documented sickle cell trait, and 1 had hemoglobin S/C disease (although sickled erythrocytes were seen in histologic sections in all cases except one). Twice as many men as women were affected in their series. Presenting features included gross or microscopic hematuria, flank pain, weight loss, and fever. The duration of clinical signs and symptoms was typically short (<5 months), and patients usually presented with advanced disease.The right kidney was involved more frequently, and tumors averaged 7 cm in largest dimension. Gross morphology included hemorrhage, necrosis, and satellite nodules. The most frequent microscopic pattern was reticular (yolk sac tumor–like); other patterns included microcystic, adenoid cystic, micropapillary, and solid sheets. Occasional cases showed tubules and spindle cells. Tumor cells had clear nuclei with prominent nucleoli and abundant cytoplasm, imparting a rhabdoid or vaguely plasmacytoid appearance. Hemorrhage and necrosis were frequent and showed neutrophilic infiltrate and microabscesses. Special stains showed variable cytoplasmic mucin (positive for mucicarmine and periodic acid–Schiff with diastase). Immunohistochemical stains for keratin and epithelial membrane antigen were strongly positive, and some tumors stained for carcinoembryonic antigen.All patients included in the original report who had available follow-up information died within 3 to 52 weeks from the time of diagnosis. Chemotherapy and radiation therapy, used in a few cases, did not appear to prolong survival.Following the original publication in 1995, several case reports have appeared in the English language literature (summarized in the Table). The clinical and radiologic findings of these cases are similar to those described by Davis et al. All patients had sickle cell trait and were of African-American descent. The longest surviving patient lived for 15 months from diagnosis.4 Most cases confirm the histochemical and immunohistochemical findings of the original article; additional studies are listed in the Table. Ultrastructural observations were first reported by Rodriguez-Jurado and Gonzalez-Crussi5 and subsequently by Larson et al6 and Wesche et al.7 Tumor cells had intracytoplasmic lumens with short microvilli. Intercellular junctions were seen, but well-formed desmosomes were not present. The cells contained bundles of tonofilaments. Intracellular mucin, glycogen, and fat were not seen. The case reported by Larson et al6 had positive urinary and gynecologic cytology. Single cells with dense granular cytoplasm, sharp cytoplasmic borders, and increased nuclear-cytoplasmic ratios were seen. The nuclei showed marked pleomorphism, irregular nuclear borders, irregularly clumped chromatin, and multiple prominent nucleoli. Papillary clusters were not seen.The differential diagnosis of RMC includes collecting duct carcinoma, transitional cell carcinoma, renal cell carcinoma, and rhabdoid tumor.1,5,6,7 The age of the patient, location, and gross morphology of the tumor are helpful in distinguishing among the differential diagnoses. Rhabdoid tumor is seen in very young children and has a monomorphic morphologic appearance, unlike RMC. Collecting duct carcinoma involves the renal medulla and pelvis and shows a predominantly tubular and papillary growth pattern. Unlike the variable patterns seen in RMC, renal cell carcinoma has clear cells or sarcomatous areas with prominent vasculature, and transitional cell carcinoma has papillary and invasive urothelial cells.The association of RMC with sickle cell trait is intriguing, but its etiopathogenetic significance is obscure at present.3 To our knowledge, the case illustrated in this article is the first reported example of diagnosis of RMC by a needle core biopsy. Hemoglobin studies in this case showed hemoglobin A/S. In view of the advanced disease and poor prognosis, aggressive therapy was not undertaken, and the patient died 4 days after being discharged to a nursing care facility. An autopsy was not performed.In the appropriate clinical setting of a young patient with sickle cell trait and a renal neoplasm, the diagnosis of RMC must be considered. In view of its extremely aggressive behavior, it is not surprising that many cases of RMC present with advanced disease, and the renal origin of the tumor may not be readily apparent before surgery.