Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma

  • Anna Caliò
  • Diego Segala
  • Guido MartignoniEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4825-1
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Definition

A high-grade carcinoma with variable architectural pattern in the same tumor, often with prominent nucleoli and perinucleolar clearing and demonstrating germline mutations in the gene encoding fumarate hydratase (FH).

Clinical Features

Patients may present with cutaneous and/or uterine leiomyomas (Reed’s syndrome) (Patel et al. 2017). Cases with somatic and not germline mutation in FH gene has been reported.
  • Incidence

    It is a rare tumor, comprising <1% of all resected tumors.

  • Age

    The mean age is around 40 years.

  • Sex

    No sex predilection has been noted.

  • Site

    There is no site predilection.

  • Treatment

    Radical nephrectomy.

  • Outcome

    The prognosis of patients with hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma is poor with tendency to early widespread dissemination.

Macroscopy

Unlike most hereditary renal cell carcinomas involving the kidneys, hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma may present as a single unilateral mass. They may show solid and cystic appearance in variable proportion.

Microscopy

A variety of morphologic patterns including papillary, tubular, tubulocystic, solid, and mixed have been described (Fig. 1). The characteristic nuclear features (large nuclei with prominent eosinophilic nucleoli) may only be present focally in the large eosinophilic cells of the tumor (Smith et al. 2016; Muller et al. 2018).

Immunophenotype

Loss of FH and overexpression of modified cysteine (2SC) are diagnostic.

Molecular Features

Germline mutations in FH have been found in 99% of the families.

Differential Diagnosis

High-grade papillary renal cell carcinoma, tubulocystic renal cell carcinoma, collecting duct renal cell carcinoma, and medullary renal cell carcinoma should be ruled out. For the differential diagnosis between hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinoma and collecting duct renal cell carcinoma and medullary renal cell carcinoma, an immunohistochemical panel including PAX8, S100A1, INI1, Oct3/4, and FH antibodies can be extremely useful (Ohe et al. 2018). A distinctive, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma, has been reported (Smith et al. 2017).
Fig. 1

A papillary architecture of the tumor (a) and loss of FH by immunohistochemistry with internal control (b)

References and Further Reading

  1. Muller, M., Guillaud-Bataille, M., Salleron, J., et al. (2018). Pattern multiplicity and fumarate hydratase (FH)/S-(2-succino)-cysteine (2SC) staining but not eosinophilic nucleoli with perinucleolar halos differentiate hereditary leiomyomatosis and renal cell carcinoma-associated renal cell carcinomas from kidney tumors without FH gene alteration. Modern Pathology, 31, 974–983.CrossRefGoogle Scholar
  2. Ohe, C., Smith, S. C., Sirohi, D., et al. (2018). Reappraisal of morphologic differences between renal medullary carcinoma, collecting duct carcinoma, and fumarate hydratase-deficient renal cell carcinoma. The American Journal of Surgical Pathology, 42, 279–292.CrossRefGoogle Scholar
  3. Patel, V. M., Handler, M. Z., Schwartz, R. A., & Lambert, W. C. (2017). Hereditary leiomyomatosis and renal cell cancer syndrome: An update and review. Journal of the American Academy of Dermatology, 77, 149–158.CrossRefGoogle Scholar
  4. Smith, S. C., Trpkov, K., Chen, Y. B., et al. (2016). Tubulocystic carcinoma of the kidney with poorly differentiated foci: A frequent morphologic pattern of fumarate hydratase-deficient renal cell carcinoma. The American Journal of Surgical Pathology, 40, 1457–1472.CrossRefGoogle Scholar
  5. Smith, S. C., Sirohi, D., Ohe, C., et al. (2017). A distinctive, low-grade oncocytic fumarate hydratase-deficient renal cell carcinoma, morphologically reminiscent of succinate dehydrogenase-deficient renal cell carcinoma. Histopathology, 71, 42–52.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Diagnostic and Public Health, Section of PathologyUniversity of VeronaVeronaItaly
  2. 2.Department of PathologyPederzoli HospitalPeschiera del GardaItaly