Renal Medullary Carcinoma in an Adolescent With Unknown Sickle Cell Trait

Renal medullary carcinoma (RMC) is an aggressive and rare malignancy that usually presents in adolescents and young adults with sickle cell disease. Herein, we describe a case of a white male with an unknown sickle cell trait, who presented with left iliac fossa pain, without any other finding that suggested renal neoplasia. Imaging findings were a renal mass of central location with caliectasis, renal hilar adenopathy, and paraaortic lymphadenopathy. Biopsy confirmed an RMC diagnosis. RMC diagnosis requires clinical suspicion in sickle cell patients who present with pain and hematuria. Imaging shows a central mass, with an infiltrative appearance, frequently associated with calyx’s dilation and lymphadenopathy. Prognosis is poor in spite of the treatment.

RMC usually affects older children or young adults with sickle cell trait or heterozygous sickle cell disease (hemoglobin [Hb] SC disease), in the age of 5-39 years (mean age 14.8 years) [4,5,6]. Homozygous Hb SS disease is not associated with RMC [4]. In patients younger than 25 years, RMC has a higher prevalence in male sex (2-3:1, M:F); no sex differences have been observed in patients older than 25 years [5][6][7].
The objective of this article is to describe the imaging findings in CMR based on an unusual case with an atypical clinical presentation.

Case Presentation
A 12-year-old male patient, with no personal medical history, presented to the ED due to 20 days of left iliac fossa pain, which increased over time. A review of systems was negative for fever, weight loss, hematuria, or any other urinary symptom. Physical examination found pain elicited by palpation in the left flank and positive fist percussion on the same side.
Abdominal ultrasound and contrast abdominal MRI showed a left renal mass, retroperitoneal lymphadenopathies in renal hilum and paraaortic location, with no evidence of metastasis (Figures 1 and 2). CT of the chest ruled out pulmonary metastasis ( Figure 3). The patient underwent nephrectomy and lymph node resection; total lymph node resection was not possible. Frozen section biopsy of the renal mass and lymph nodes suggested malignant neoplasia, not suggestive of lymphoma; RMC diagnosis was subsequently confirmed, with an absence of INI1 expression, and positive for EMA, AE1/AE1, and vimentin ( Figure 4). Due to the strong relationship between RMC and sickle cell disease, Hb electrophoresis was performed, confirming a Hb SC disease. Platinum-based chemotherapy was initiated with no radiotherapy. The patient is alive four months after the diagnosis, with persistent retroperitoneal lymph nodes in the last imaging follow-up with MRI ( Figure 5).

FIGURE 1: Abdominal ultrasound.
Abdomen ultrasound with low-frequency convex transducer (A and F) and high-frequency linear transducer (C and E). Solid renal lesion of central location (arrow in A, B, and C), generating focal caliectasis in both superior and inferior pole (arrowhead in A, B, C, D, and E). It was hypovascular in color Doppler mode (B and D). Additionally, retroperitoneal lymphadenopathies were observed in paraaortic and renal hilum locations (arrow in F).
Imaging identifies a centrally located mass, with rapid growth and infiltrative, ill-defined margins, that can extend to the renal cortex and sinus. Even though there is a renal expansion of the mass, a renal configuration is conserved. Ultrasound shows a solid mass with caliectasis but no pyelectasis, with no vascularization in color flow Doppler, and minimum peritumoral vascularization in the power Doppler mode. It is worth remarking that some tumors may not be detected through ultrasound [1,2,6,8,10]. Angiography shows the hypovascular nature of the tumor [3,6]. RMC is usually heterogeneous on CT and MRI due to necrosis areas, and lower enhancement than the adjacent renal parenchyma is typical [6,10]. The tumor may extend onto perirenal fat tissue, and it is associated with distant metastasis. Lymphadenopathy and vascular invasion are common [3,6]. MRI is superior to CT to detect both hemorrhage and hepatic metastasis [8].
Differential diagnosis includes multiple diseases. Renal lymphoma usually has an infiltrative pattern, with multifocal and bilateral involvement, associated with diffuse lymphadenopathy and multiple organ involvement. Rhabdoid tumor and mesoblastic nephroma must be distinguished from RMC, as these tumors usually present in younger patients. Even though it is infrequent in adolescents, Wilms' tumor must be taken into account in the differential diagnosis. Transitional cell carcinoma and renal cell carcinoma may look like RMC, but a loss of the SMARCB1 gene, and the association with sickle cell trait, suggest RMC. Finally, RMC may simulate pyelonephritis; therefore, history and physical examination are essential for proper diagnosis [1,2,6,10]. Age and sickle cell trait history may help to perform the correct diagnosis of RMC [6,10].
When a diagnosis is performed, the advanced disease is usually found [1,10], with hepatic, pulmonary, and lymphatic metastasis. Prognosis is poor, and survival after surgical intervention is of 4-5 months in cases with metastasis [1,2,6], with an overall mortality rate of 95% [1,2].

Conclusions
RMC is an infrequent tumor of aggressive behavior, with a predilection for young patients with sickle cell trait or heterozygous sickle cell disease. Our case shows an unusual presentation in a white adolescent with unknown Hb SC disease. Imaging findings consist of a centrally located mass invading the renal sinus with peripheral caliectasis, but renal morphology is preserved. The prognosis of this disease is usually poor, despite treatment.

Additional Information Disclosures
Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.