Case Report
An Unexpected Case of Small Cell Neuroendocrine Carcinoma of the Ureter
Annah Vollstedt1*, Cristina Taylor,2 and Amichai Kilchevsky2
1Department of Urology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
2Department of Urology, Concord Hospital, Concord, NH, USA
*Corresponding author: Annah J. Vollstedt, Department of Urology, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA
Published: 20 Mar, 2018
Cite this article as: Vollstedt A, Taylor C, Kilchevsky A.
An Unexpected Case of Small Cell
Neuroendocrine Carcinoma of the
Ureter. Clin Surg. 2018; 3: 1941.
Abstract
With less than 30 cases reported in the literature, primary upper tract small cell neuroendocrine
tumors are extremely rare. An 84-year-old woman with a history of ovarian carcinoma treated
surgically and with adjuvant chemotherapy presents with right hydronephrosis discovered on
surveillance imaging. Thought to be due to extrinsic compression, a ureteral stent was placed
followed by routine exchanges until stent failure prompted ureteroscopy, which showed a mass in
the mid ureter.
Keywords: Small cell neuroendocrine carcinoma; Upper tract
Introduction
Small cell neuroendocrine tumors are most commonly found in the lung, small intestine, adrenal gland and the thyroid. Primary small cell small cell neuroendocrine can also be found in the urinary tract, accounting for 0.7% of all bladder tumors [1] and less than 0.05% of all urinary tract malignancies [2]. Small cell neuroendocrine carcinoma of ureteral origin is extremely rare with fewer than 30 cases reported in the literature [3-6]. We report a case of primary small cell neuroendocrine carcinoma, initially presenting as ureteral obstruction of unknown etiology.
Case Presentation
We report a case of an 84-year-old woman with a history of Stage IIIC high grade serous ovarian
carcinoma four years prior treated with total hysterectomy, pelvic lymphadenectomy, omentectomy
and partial colon resection, as well as 6 cycles of carboplatin and paclitaxel chemotherapy. She was
then randomized to the clinical trial AMG 386 for 18 months, which was completed in January
2015. In December of 2015, she underwent routine surveillance imaging, revealing new right-sided
hydronephrosis (Figure 1). This was thought to be due to retroperitoneal fibrosis caused by her prior
chemotherapy or due to ureteral stricture disease from her previous abdominal surgery.
A right retrograde pyelogram and right ureteral stent placement was performed in January
2016. Due to her spinal hardware, a clear location of her obstruction was not identified (Figure 2).
She underwent a routine stent exchange 6 months later in July 2016.
In November 2016 at the routine follow-up with her gynecologist-oncologist, she was found to
have increased right-sided hydronephrosis with deterioration in her renal function with a serum
creatinine of 1.38 mg/dL from a baseline of 0.89 mg/dL. There was no evidence of recurrence of
ovarian cancer on positron emission tomography scan and her cancer antigen-125 levels remained
normal.
She then underwent a right retrograde pyelogram, ureteroscopy and stent exchange the following
month. Retrograde pyelogram showed a massively dilated collecting system. Ureteroscopy revealed
a fleshy mass within the mid right ureter. Cytology was collected and the mass was biopsied.
Hematoxylin and eosin stains showed small biopsy specimens containing crowded small to
medium sized cells with indistinct cell borders and crush artifact in a background of scant stroma.
Nuclei displayed hyper chromatic chromatin with indistinct nucleoli, nuclear molding and
apoptotic debris. Due to the scant nature of the specimens limited immunohistochemical stains
were performed but revealed positivity for synaptophysin. The case was reviewed at another major
medical center, who also confirmed the diagnosis of small cell neuroendocrine tumor. (Figure 3-5).
After review of the small number of case reports, as well as extrapolating from the literature regarding small cell carcinoma of the bladder, conferring with our institution’s multi-institutional tumor board, and counseling the
patient, the treatment plan is for carboplatin chemotherapy with
radiation. Follow-up imaging in May 2017 showed improved rightsided
hydronephrosis and no evidence of metastatic disease.
Figure 1
Figure 1
New right-sided hydronephrosis seen on routine CT scan
performed for follow-up of ovarian carcinoma.
Figure 2
Figure 2
Right retrograde pyelogram. Clear source and location of
obstruction not identified due to poor visualization secondary to spinal
hardware.
Figure 3
Figure 4
Figure 5
Discussion
The exact etiology of neuroendocrine tumors is difficult to discern
due to its rarity in the medical literature. However, it is hypothesized
that urothelial cells may undergo a transformation to neuroendocrine
cells or perhaps there is presence of trapped neural crest cells during
embryological development [4].
The clinical presentation of primary small cell neuroendocrine
carcinoma of the upper tract is similar to that of other upper tract
tumors: flank pain hematuria, weight loss, fatigue. Unlike other
more common primary neuroendocrine tumors, primary small cell
neuroendocrine carcinoma of the urinary tract is not associated with
paraneoplastic syndromes [7].
Histologically, small cell neuroendocrine tumors are characterized
by small to medium sized round/oval cells with minimal cytoplasm
and indistinct cell borders. Nuclei displayed hyperchromatic
chromatin with indistinct nucleoli, nuclear molding, mitotic figures
and apoptotic debris. Crush artifact is common and characteristic of
these delicate tumor cells. Immunohistochemical stains can also be
helpful in the diagnosis. Classically, these tumors are positive for both
chromogranin A and synaptophysin. In our case, the staining was
negative for chromogranin; however, the positivity for synaptophysin
in conjunction with the classic histomorphological features was
enough to make the diagnosis of small cell neuroendocrine carcinoma.
The largest meta-analysis of upper tract small cell neuroendocrine
carcinoma reported a median age of presentation for upper tract
small cell neuroendocrine carcinoma is 66.5 years with most patient
presenting with either pT3 or pT4 disease. An aggressive disease, 54%
of patients was reported to develop metastasis within 13 months of
original diagnosis [4].
The treatment for small cell neuroendocrine carcinoma is
extrapolated mostly from treatment of small cell carcinoma of the
lung and is typically a multimodal approach, including surgery,
radiation and adjuvant platinum-based chemotherapy. Median
survival is reported to range from 8.2 to 23 months [1,3,4].
Interestingly, in our case, the patient’s right-sided hydronephrosis
was incidentally found, and then misdiagnosed initially as either
extrinsic compression of the ureter due or ureteral stricture disease from her previous extensive gynecological surgery. Sood et al. [5]
also describe a similar situation of a woman diagnosed with primary
ureteral small cell neuroendocrine carcinoma with a prior history
of stage 1B mixed clear cell-endometroid cancer of uterus, treated
with hysterectomy and adjuvant radiation. Both cases demonstrate
the importance of having a high index of suspicion for less common
reasons for radiographic hydronephrosis or clinical symptoms of
obstruction.
Conclusion
Primary small cell neuroendocrine of the upper tract is a rare diagnosis. Diagnosis may be difficult initially, especially when other reasons for radiographic or clinical obstruction may be more likely. The paucity of literature makes for difficult treatment decision. More systematic study of treatments and outcomes for this rare condition would help guide management of future cases.
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