Expanding the Spectrum of Colonic Manifestations in Tuberous Sclerosis: L-Cell Neuroendocrine Tumor Arising in the Background of Rectal PEComa

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous condition that predisposes to numerous proliferative lesions, including perivascular epithelioid cell tumors (PEComas), such as lymphangioleiomyomatosis (LAM) and angiomyolipomas, and rare neuroendocrine neoplasms. We describe herein a TSC2-harboring tuberous sclerosis patient manifesting with a synchronous well-differentiated L-cell rectal neuroendocrine tumor and leiomyomatosis-like LAM of the rectum. The background large bowel wall was thickened by confluent nodular areas comprising vessels and spindle-to-epithelioid cells, which are immunoreactive for myoid (smooth muscle actin, muscle specific actin, and desmin) and melanocytic markers (HMB45, Melan-A, microphthalmia transcription factor, and CD117). With the exception of TSC-related pancreatic neuroendocrine tumors, the association between tuberous sclerosis and neuroendocrine neoplasms remains largely unknown in the gastrointestinal tract. Neuroendocrine tumorigenesis in tuberous sclerosis is often linked to inactivating mutations of TSC2 leading to aberrant activation of mammalian target of rapamycin (mTOR) pathway. In this report, we document, for the first time, two foci of L-cell rectal neuroendocrine tumor arising in the setting of tuberous sclerosis, thus broadening the spectrum of TSC-associated endocrine disorders. Moreover, to our knowledge, this is only the second documented case of gastrointestinal leiomyomatosis-like LAM in a patient with tuberous sclerosis. The current case provides further evidence that, similar to pancreatic neuroendocrine tumors, neuroendocrine tumors of the luminal gastrointestinal tract may also be a feature of tuberous sclerosis and can be seen in association with PEComas.