Primary Ureteral Thyroid Transcription Factor 1–Positive Small Cell Neuroendocrine Carcinoma

Abstract

Upper urinary tract neoplasms comprise only 5% of urinary malignancies overall, the overwhelming majority showing an urothelial histology. Nonurothelial lesions represent 1.9% of upper tract neoplasms, and small cell carcinomas (SmCCs) only account for a minute fraction of them, with few cases reported in the literature to date. In the genitourinary tract, these lesions are most frequently found in the urinary bladder, where they tend to show a mixed histology with a characteristic small cell neuroendocrine component that is positive for chromogranin A, synaptophysin, and CD56 immunostains. Urinary SmCCs are almost invariably aggressive, with a propensity to infiltrate surrounding tissues and vascular structures. Unfortunately, clinical stage at presentation is often advanced, with early dissemination to lymph nodes or distant organs in a significant proportion of patients. For the most part, prognosis is dismal and can be predicted by the pathologic stage at diagnosis. Recently, new chemotherapeutic regimens have shown some potential benefit for the treatment of urinary SmCC, albeit not achieving curative results. Here we present the case of a 71-year-old male patient with a history of treated bladder urothelial carcinoma that presented with subacute flank pain and was diagnosed with a primary pure SmCC of the ureter. Besides the usual neuroendocrine immunomarkers, this tumor showed intense positivity for TTF-1 (thyroid transcription factor-1), a phenomenon that has been described for extrapulmonary SmCC of other locations.

Incidental finding of a small cell neuroendocrine carcinoma of the ureter

“…The nuclei are hyperchromatic with inconspicuous nucleoli, and show nuclear moulding, mitotic figures, apoptotic debris and possibly crush artefact. In addition, immunohistochemical staining can be positive for chromogranin, CD56, synaptopysin and neuron-specific enolase, and electron microscopy shows electron-dense granules 1–3 7 10–12. The presence of all these findings may not be present to confirm diagnosis, rather positivity to some of the stains and obvious morphological feature should suffice as evident, such as in our patient.…”

“…The urinary tract is a rare site for NETs and has an incidence of only 0.05%. In these cases they are usually found in the bladder, and are mostly aggressive with a potential to invade surrounding tissue and vascular structures 1–3. This makes the ureter an extremely rare site for neuroendocrine carcinomas, hence scarce reporting in the world literature; we estimate there have been less than 30 cases reported to date1–10…”

“…When present in the ureter, they mostly exhibit a typical morphological small cell neuroendocrine appearance1 2 but can also have a large cell appearance although this appears to be even rarer 8. The prognosis of ureteric NET is very poor although a multimodal treatment approach, including surgery, radiotherapy, platinum-based adjuvant or neoadjuvant chemotherapy, has been used, which may offer some respite and prevent extensive metastasis 1 5 6 10.…”

“…Small cell ureteric neuroendocrine carcinoma runs a silent course and in majority of patients present after early spread to lymph nodes and distant organs 2 3 5. The most common presenting complaints remain gross haematuria and flank pain 2–7.…”

Primary small cell carcinoma of the upper urinary tract: A case report

“…Histologic features of upper tract NE tumors are similar to those outside of the urinary tract including scant-moderate cytoplasm, fine speckled chromatin, and high nucleocystoplasmic ratio 5 . These tumors typically stain positive for CAM 5.2, synaptophysin, chromogranin A, pancytokeratin (AE1/AE3), CD56, and/or neuron-specific enolase 4 , 5 .…”