Unusual Sites of High-Grade Neuroendocrine Carcinomas: A Case Series and Review of the Literature

Abstract

BACKGROUND Neuroendocrine tumors (NETs) encompass a diverse group of varying clinicopathological entities arising from cells of the endocrine and nervous systems. The presentation of these unique tumors can range from occult disease discovered incidentally to hyperactive, metastatic secretory tumors. NETs most commonly originate in the gastrointestinal and respiratory tract, although they may occur at any site in the body due to the wide distribution of neuroendocrine cells. Their classification system is complex and continues to evolve, and the current system uses histological grade in defining these subtypes. Neuroendocrine carcinomas (NECs), or high-grade, poorly-differentiated NETs, are the most aggressive subtype. Surgical resection remains the primary treatment modality and may be curative, thus early diagnosis is paramount. Management of advanced NETs remains both a diagnostic and therapeutic challenge; however, advances in our understanding of these unique neoplasms as well as an evolving classification system has led to the development of adjunctive therapeutic approaches aimed to minimize morbidity and improve patient outcomes. CASE REPORT We present 6 cases of unusual sites of high-grade neuroendocrine carcinomas involving the cervix, gallbladder, oesophagus, ovary, prostate, and urinary bladder. CONCLUSIONS Our case series highlights the heterogenous and aggressive nature of this subtype of NETs as well as their diagnostic and therapeutic difficulties. We also review the evolution of the NET classification system and its impact on the management of these malignancies.

Figure 1.

MRI pelvis. Sagittal (A) and coronal (B) section demonstrating a large exophytic lesion (red arrow) arising from the lower cervix and distending and distorting the endocervical canal, which is in intimate contact with the external os. The lesion measures at least 72×43 mm, extending to the lower cervix, and on the sagittal images extending into the upper vagina.

Figure 2.

Small-Cell neuroendocrine carcinoma of the cervix. The tumor cells consist of diffuse sheets of small malignant cells (A) with extensive necrosis (B) and frequent mitotic activity (C). Immunohistochemistry shows positivity for neuroendocrine marker CD56 (D).

Figure 3.

Small-cell neuroendocrine carcinoma of the gallbladder. Histopathological examination of the gallbladder specimen reveals involvement of all layers of the gallbladder wall and focal tumor necrosis (A, B). On Immunohistochemistry, CD 56 shows diffuse positive membranous staining (C) and Ki 67 shows a high proliferation rate with almost 100% staining (D).

Figure 4.

Transaxial CT image demonstrates a large hypoenhancing area in the medial aspect of the left hepatic lobe predominantly involving segment 4B (red arrow). Lymphadenopathy involving the nodes in the porta hepatis is also noted.

Figure 5.

High-grade neuroendocrine carcinoma of the oesophagus with liver metastases. Histopathological analysis of the biopsied liver lesion reveals appearances consistent with metastatic high-grade neuroendocrine carcinoma (A). On immunohistochemistry there is positivity for epithelial marker CK 7 (B) and neuroendocrine marker CD 56 (C). Ki-67 shows a high proliferative index (D).

Figure 6.

Transaxial section demonstrates circumferential thickening of the wall of the mid-oesophagus (red arrow), corresponding to the site of the ulcer discovered on endoscopy. There are also enlarged lymph nodes in the aorto-pulmonary window and paraaortic regions.

Figure 7.

CT Brain with contrast demonstrates one of many bilateral enhancing lesions in the cerebrum (red arrow), compatible with multiple metastases.

Figure 8.

CT Coronal (A) and sagittal (B) sections. There is a large soft-tissue mass measuring 17×91 mm in the pelvis, involving the serosa of the sigmoid colon and rectum and obscuring the uterus and ovaries (red arrows), as well as mass effect on the bladder. There is also large-volume intra-abdominal ascites with peritoneal nodularity consistent with intra-abdominal spread of malignancy.

Figure 9.

Histopathological analysis of the pelvis mass biopsy reveals dense sheets of small cells with scanty cytoplasm, hyperchromatic nuclei, frequent mitoses, and inconspicuous nucleoli, consistent with small-cell carcinoma (A, B). On immunohistochemistry, CK AE1/AE3 shows positive staining (C) and WT-1 is also positive (D).

Figure 10.

High-grade neuroendocrine carcinoma of the prostate. Histopathological analysis reveals the presence of prostatic neuroendocrine carcinoma in practically all biopsy specimens (A, B). On immunohistochemistry, synaptophysin shows positive cytoplasmic staining (C) and CD56 shows positive membranous staining (D).

Figure 11.

MRI pelvis demonstrates a stage T3b N2 Mx lesion of the prostate, gland volume 37 cc (red arrow). The right seminal vesicle and right neurovascular bundle are involved by disease. Left para-aortic, right internal iliac, and left external iliac lymphadenopathy are also shown.

Figure 12.

CT Pelvis demonstrates thickening along the central and right lateral aspect of the urinary bladder fundus, consistent with the previous location of the bladder tumor (red arrow), with induration of surrounding fat.