Hereditary leiomyomatosis and renal cell cancer syndrome - case report and review of the literature

Abstract

Hereditary leiomyomatosis and renal cell cancer syndrome (HLRCC) is an exceptionally rare autosomal dominant condition caused by a germline heterozygous mutation of the fumarate hydratase gene. It manifests as multiple piloleiomyomas, associated with numerous, early-onset uterine leiomyomas in female patients, as well as a highly increased risk of renal cell carcinoma (RCC), most often type 2 papillary RCC. HLRCC has been described in association with adrenal cortical hyperplasia, pheochromocytoma, adrenal cortical carcinoma, and other solid tumors, but the exact relationship between these disorders has not yet been clarified. We present a case of HLRCC associated with bilateral adrenal cortical hyperplasia and discuss the pathogenesis, clinical and paraclinical features of HLRCC, as well as the adequate management of these patients.

Figure 1

Multiple skin colored, smooth papules and nodules, 0.3–2 cm in diameter, located on the upper limb

Figure 2

Multiple piloleiomyomas located on the trunk

Figure 3

(A and B) Dermal tumor composed of smooth muscle fibers, peri- and intratumoral minimal inflammatory lymphocytic infiltrate, intertwined with collagen bundles. The overlying epidermis is atrophic, with flattened rete ridges and hyperpigmentation of the basal layer. Hematoxylin–Eosin (HE) staining: (A) ×50; (B) ×100

Figure 4

(A and B) Dermal tumor composed of smooth muscle fibers, with yellow cytoplasm, minimal nuclear and cytoplasmic pleomorphism, perinuclear cytoplasmic vacuolization, peri- and intratumoral minimal inflammatory lymphocytic infiltrate, interlaced with collagen fibers. Van Gieson staining: (A) ×50; (B) ×100

Figure 5

(A–D) Immunohistochemical staining showing diffuse positivity for actin (A, ×50) and vimentin (B, ×50), positivity for CD34 limited to endothelial cells (C, ×100) and for Leu7 limited to nerve fibers (D, ×100). CD34: Cluster of differentiation 34