PATHOLOGY

Renal medullary carcinoma: report of seven cases from Brazil
Watanabe IC, Billis A, Guimarães MS, Alvarenga M, de Matos AC, Cardinalli IA, Filippi RZ, de Castro MG, Suzigan S
State University of Campinas, São Paulo, Brazil
Mod Pathol. 2007; 20: 914-20

• We report seven cases of renal medullary carcinoma collected from several institutions in Brazil. In spite of a relatively high incidence of sickle cell trait in Brazil, this is a rare tumor. All patients were males between the ages of 8 and 69 years (mean 22 years). From the collected information, the most frequent presenting symptoms were gross hematuria and flank or abdominal pain. The duration of symptoms ranged from 1 week to 5 months. Most of the tumors were poorly circumscribed arising centrally in the renal medulla. Size ranged from 4 to 12 cm (mean 7 cm) and hemorrhage and necrosis were common findings. All seven cases described showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. All cases disclosed the characteristic reticular pattern consisting of tumor cell aggregates forming spaces of varied size, reminiscent of yolk sac testicular tumors of reticular type. Other findings included microcystic, tubular, trabecular, solid and adenoid-cystic patterns, rhabdoid-like cells and stromal desmoplasia. A peculiar feature was suppurative necrosis typically resembling microabscesses within epithelial aggregates. The medullary carcinoma of the 69-year-old patient was associated with a conventional clear cell carcinoma. To our knowledge, this association has not been previously reported and the patient is the oldest in the literature. The survival after diagnosis or admission ranged from 4 days to 9 months. The 8-year-old African-Brazilian patient with a circumscribed mass is alive and free of recurrence 8 years after diagnosis. This case raises the question whether a periodic search for renal medullary carcinoma in young patients who have known abnormalities of the hemoglobin gene and hematuria could result in an early diagnosis and a better survival.
  
  
• Editorial Comment
  Renal medullary carcinoma is a rare, rapidly growing tumor that affects young individuals with sickle cell trait. This tumor was described in 1995 by Davis et al. (1), which considered it the seventh sickle cell nephropathy. The six sickle cell nephropathies previously described by Berman (2), in 1974, are gross hematuria, papillary necrosis, nephrotic syndrome, renal infarction, inability to concentrate the urine and pyelonephritis. All of them are to a certain extent related to the obstruction of blood vessels and tissue hypoxia resulting from red blood cell sickling. The renal medulla is particularly susceptible to damage in sickle cell disease due to its unique environment characterized by anoxia, hyperosmolarity and low pH that tend to promote hemoglobin S polymerization and red blood cell sickling. Over a period of 22 years, the Armed Forces Institute of Pathology had collected only 34 cases (1) and over the next 5 years, only 15 more had been described (3).
  The incidence of sickle cell trait in Brazil is 6.7% in African-Brazilians, 5.4% in Mulattos (persons with mixed White and African-Brazilian ancestry) and 0.21% in Whites (4). Considering the large population at risk, the tumor is, in fact, very rare suggesting that additional factors are likely necessary. This is the first report from Brazil as a result of the collaboration of several pathologists that searched for cases of renal medullary carcinoma in their institution’s files.
  Renal medullary carcinoma is typically seen in young patients with the sickle cell trait and exceptionally with sickle cell disease. All seven cases described in the study showed sickled red blood cells in the tissue and six patients were confirmed to have sickle cell trait. Renal medullary carcinoma shows a male predominance (2:1) and the mean age at presentation is approximately 22 years, with ages ranging from 5 to 40 years.
  The most frequent presenting symptoms are gross hematuria and flank or abdominal pain. A palpable abdominal mass is often observed. Some patients may present with symptoms of metastatic disease. Spontaneous gross hematuria, the first sickle cell nephropathy, is usually unilateral and occurs at the same age range that renal medullary carcinoma. It is worth noting, however, that most of these spontaneous benign bleedings occur from the left kidney and most of the renal medullary carcinomas arise on the right kidney. The origin and pathogenesis of renal medullary carcinoma are not completely understood.
  The prognosis of renal medullary carcinoma is very poor due to the highly aggressive behavior of this neoplasm and to its resistance to conventional chemotherapy. Metastases are both lymphatic and hematogenous with liver and lungs most often involved. The mean duration of life after surgery is about 15 weeks (5) and the longest documented survival for renal medullary carcinoma was 15 months (6). Exceptionally, the 8-year-old African-Brazilian patient with a circumscribed mass described in the study is alive and free of recurrence 8 years after diagnosis. Chemotherapy has been known to prolong survival by few months but generally, neither chemotherapy nor radiotherapy has altered the course of the disease (7).

References
1. Davis CJ Jr, Mostofi FK, Sesterhenn IA: Renal medullary carcinoma. The seventh sickle cell nephropathy. Am J Surg Pathol. 1995; 19: 1-11.
2. Berman LB: Sickle cell nephropathy. JAMA. 1974; 228: 1279.
3. Khan A, Thomas N, Costello B, Jobling L, deKretser D, Broadfield E, et al.: Renal medullary carcinoma: sonographic, computed tomography, magnetic resonance and angiographic findings. Eur J Radiol. 2000; 35: 1-7.
4. Chapadeiro E, Maciel R, Jamra M, et al.: Linfonodos, Baço, Medula Óssea e Sangue. Tumores do Sistema Hemolinfático. Timo. In: Lopes ER, Chapadeiro E, Raso P, Tafuri WL (eds), Bogliolo Patologia. 4th ed. Rio de Janeiro, Guanabara Koogan. 1987; pp. 651-2.
5. Davis Jr CJ: Renal medullary carcinoma. In: Eble JN, Sauter G, Epstein JI, et al. (eds), World Health Organization Classification of Tumours. Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs. Lyon, IARC Press. 2004; pp.162-92.
6. Swartz MA, Karth J, Schneider DT, Rodriguez R, Beckwith JB, Perlman EJ: Renal medullary carcinoma: clinical, pathologic, immunohistochemical, and genetic analysis with pathogenetic implications. Urology. 2002; 60: 1083-9.
7. Pisani P, Bray F, Parkin DM: Estimates of the world-wide prevalence of cancer for 25 sites in the adult population. Int J Cancer. 2002; 97: 72-81.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil