Neuroendocrine Neoplasms of the Female Genitourinary Tract: A Comprehensive Overview

Abstract

Primary neuroendocrine neoplasms are a rare heterogeneous group of tumors that include well-differentiated neuroendocrine tumors, poorly differentiated neuroendocrine carcinoma, and paraganglioma. An extensive literature search was used to compile the data regarding epidemiology, pathogenesis, imaging features, and management of the urinary system NENs. We also included the updated staging of the NENs at various locations of the urinary system.

Keywords: cancer staging; female neuroendocrine neoplasms; genitourinary NENs; imaging of neuroendocrine tumors; neuroendocrine tumors.

Figure 1

Illustration demonstrating the structures of the normal female genitourinary tract.

Figure 2

Illustration of renal neuroendocrine carcinoma. (A) T1: tumor limited to kidney and ≤7 cm in greatest dimension; (B) T2: tumor limited to kidney and >7 cm in dimension; (C) T3: tumor extending into the major vein or the tissue around the kidney; (D) T4: tumor growth beyond the Gerota’s fascia and may be growing into the adrenal gland.

Figure 3

A 36-year-old female with renal NENs. CT of the abdomen before (A) and after oral and IV contrast administration in (B) arterial, (C) porto-venous, and (D) delayed phases reveal a 5.3 × 3.9 cm partially calcified mass (arrows) arising from the left kidney, extending to the left perinephric space, and abutting the tail of the pancreas. Pathology revealed small-cell carcinoma with neuroendocrine differentiation.

Figure 4

A 45-year-old female with renal NENs. MRI axial T1 (A) in phase, (B) out of phase, (C) 3D axial, (D) T2, (E) T2 fat saturation, (F) coronal T2, (G) post-contrast dynamic, (H,I) dynamic subtraction images, (J) delayed postcontrast axial, (K) DWI, and (L) ADC show a large right renal mid and lower pole mass (arrows) measuring 6.6 × 7.1 cm showing central enhancing solid component with restricted diffusion and peripheral cystic component. Pathology revealed a neuroendocrine tumor. (M) Axial fused PET/CT images using Gallium 68 Dotatate show heterogeneously avid DOTATATE uptake of the mass (arrow), in keeping with biopsy-confirmed right kidney neuroendocrine carcinoma.

Figure 5

A 57-year-old female with renal NENs. CT scan of the abdomen before (A) and after oral and IV contrast administration in arterial (B) and porto-venous (C) phases reveal a right renal upper polar well-defined mass (arrow) with flecks of calcifications, measuring 5 × 4 cm encroaching on the right perinephric space without appreciable involvement of the right renal hilum. Pathology revealed well-differentiated neuroendocrine carcinoma (atypical carcinoid).

Figure 6

Treatment algorithm of renal malignancies.

Figure 7

Well-differentiated NET (neuroendocrine tumor). (A) Grade 1 shows packets of neuroendocrine cells separated by fibrovascular tissue. (B) Ki67 immunohistochemical stain shows a proliferation rate of 1%. Grade 2 well-differentiated NET showing (C) trabecular architecture. (D) Ki67 immunohistochemical stain shows a proliferation rate of 15%. Grade 3 well-differentiated NET with a (E) solid and nested pattern. (F) Ki67 immunohistochemical stain shows a proliferation rate of 30%. Poorly differentiated neuroendocrine carcinoma. (G) The tumor shows solid nests of poorly differentiated epithelioid cells with elevated nuclear size, pleomorphism, and dense chromatin. Notice there is necrosis in the center of the image. (H) Ki67 immunohistochemical stain shows a proliferation rate of 80%. Small cell neuroendocrine carcinoma (I) sheets of small to medium, round/oval, blue cells with minimal cytoplasm. The chromatin is finely dispersed. (J) Nuclei demonstrate molding. Ki67 shows a proliferation index of 80%. Large cell neuroendocrine carcinoma (K) with organoid architecture. Large cells (~3× size of small-cell carcinoma) are present with abundant cytoplasm, variably coarse chromatin, nuclear pleomorphism, and prominent nucleoli. (L) Ki67 immunohistochemical stain shows a proliferation rate of 90%.

Figure 8

A 40-year-old female with urinary bladder NENs. Axial CT (A) pre-contrast and (B) delayed post-contrast images with coronal reconstruction (C) pre-contrast and (D) post-contrast reveal a 4.8 × 2.5 cm mass (arrows) at the proper aspect of the urinary bladder, showing faint peripheral calcification. Pathology revealed a neuroendocrine tumor of the urinary bladder.

Figure 9

A 32-year-old female with urinary bladder NENs. Axial CT post-contrast (A) shows soft tissue thickening (arrow) mounting to mass formation involving the right lateral and posterior urinary bladder wall. (B,C) It is seen narrowing (arrow in (B)) the right ureterovesical junction with secondary mild right hydroureteronephrosis (arrow in (C)). This mass seems to infiltrate the perivesical fat. A catheter balloon is seen within the bladder lumen. Pathology of the group revealed urothelial carcinoma with neuroendocrine features and focal glandular differentiation, high grade.

Figure 10

A 48-year-old female with urinary bladder NENs. Axial CT without contrast (A), axial (B), and coronal (C) reconstruction fused PET/CT images show thickened urinary bladder wall (arrows), which is most evident on the left side. The maximum thickness measures 2.4 cm and has an SUV of 8.2. Pathology revealed small-cell neuroendocrine carcinoma of the urinary bladder.

Figure 11

Staging of urinary bladder neuroendocrine carcinoma. Ta: non-invasive carcinoma; Tis: carcinoma in situ (Flat-tumor); T1: tumor invasion into subepithelial connective tissue; T2a: tumor invasion into superficial muscularis propria; T2b: umor invasion into deep muscularis propria; T3a: microscopic invasion of peri-vesical tissue; T3b: macroscopic invasion of peri-vesical tissue (extravesical mass); T4: tumor invasion of adjacent structures, pelvic or abdominal wall.

Figure 12

Treatment algorithm for urinary bladder carcinoma.

Figure 13

A 48-year-old female with ureteral NENs. (A) Coronal T2 nonfat sat image shows a large expansible hematoma in the ureteric stump (arrows). (B) Coronal T1 postcontrast delayed fat sat image: Shows a large expansible hematoma with intrinsic high T1 signal. (C) Axial T1 postcontrast delayed fat sat subtraction image: a small enhancing nodule (arrows) along the superior aspect of the stump. (D) Left lower ureter mass consists of a segment of the ureter with an attached firm, tan-brown, irregular, mass, measuring 11.5 × 7.0 × 6.0 cm. (E) E&H staining: 20× shows polypoid tumor bulging into the ureter lumen. Normal urothelial mucosa and muscle layer can be seen on the top half (arrow). (F) H&E straining: 200× high-power view shows tumor cells arranged in a trabecular and tubular pattern. (G) Synaptophysin staining: 200× shows tumor cells expressing synaptophysin (brown staining), which is a marker of neuroendocrine differentiation.

Figure 14

Treatment algorithm for upper urinary tract carcinoma.

Figure 15

Illustration demonstrating the staging of ureteral carcinoma. Ta: non-invasive papillary tumor; T1: tumor invasion into sub-epithelial connective tissue through lamina propria; T2: tumor invasion into muscularis propria; T3: tumor invasion into periureteric fat beyond muscularis propria; T4: tumor invades adjacent organs or through the kidney into the perinephric fat.

Figure 16

Staging of urethral neuroendocrine carcinoma. (A) Sagittal view of the tumor spread (B) Urethral site specific tumor spread. Ta: non-invasive papillary, polypoid, or verrucous carcinoma; Cis: carcinoma in situ; T1: tumor invasion into subepithelial connective tissue; T2: tumor invasion into periurethral muscles; T3: tumor invasion into anterior vagina or bladder neck; T4: tumor invasion into adjacent organs such as the bladder and rectum.