Primary neuroendocrine tumors of the kidney are a rare entity, with the literature being confined to scattered case reports and small case series. Outcome of such tumors in horseshoe kidneys have traditionally been reported to be better than their counterparts in non-horseshoe kidneys [1,2]. The authors here report a similar case of primary neuroendocrine tumor of the left moiety of an incidentally discovered horseshoe kidney. The patient had metastases to brain and ovaries at time of presentation.  highlighting the fact that these tumors may not in fact be as indolent as made to believe.

CASE REPORT

A 38 year old premenopausal female presented with complaints of non specific pain abdomen of 3 months duration. Clinically, the patient was found to have two separate intra abdominal masses. One was in the left lumbar area extending into the umbilical area. The other was in the hypogastric region arising from pelvis. CECT Scan of abdomen and pelvis demonstrated a horseshoe kidney, with a 13x11x11cm mass lesion within it, predominantly on the left side, which was well defined, heterogeneously enhancing and with punctate calcifications (Figure 1A). There was a 8x8x5cm (Rt) ovarian mass, without any surrounding infiltration (Figure 1B).There was no retroperitoneal lymphadenopathy, metastases to liver or lungs. Both lesions were FDG avid on a FDG-PET scan. Tumor markers, CA-125, AFP, bHCG were normal. The patient thereafter underwent Exploratory Laparotomy. An intraoperative ultrasonography confirmed absence of metastases to liver. The renal tumor was excised in toto with nephron sparing approach and the ovarian tumor was removed with total abdominal hysterectomy with bilateral salpingo-oophorectomy and omentectomy .The final histopathology revealed poorly differentiated malignant cells in sheets, cords and trabeculae having hyperchromatic chromatin and prominent nucleoli, both in the renal and ovarian masses (Figure 2). Immunohistochemical staining of the tumor was performed in both the ovarian and renal tissue. The tumor stained positive for Synaptophysin, Chromogranin, EMA and Neuron Specific Enolase (Figure 3) and negative for Leukocyte Cell Antigen and Vimentin. Hence a diagnosis of a neuroendocrine tumor was made. Patient underwent adjuvant chemotherapy with 6 cycles of Inj Etoposide and Inj Paclitaxel At a follow-up visit after one year post- surgery , though the patient was still asymptomatic , an ultrasound of abdomen revealed a possible local recurrence in the left moiety of the horseshoe kidney, confirmed on CECT (Figure 4), and positive on PET and octreotide scans. Chromogranin levels were still within normal limits .While on workup, she developed severe headache and an episode of seizures. An MRI of the brain showed multiple SOLs in the brain suggestive of metastases. She received palliative EBRT to the brain (30 Gy in 10 fractions), and oral Somatostatin. However, the patient failed to recover completely, and ultimately succumbed to her brain metastases.


Figure 1. Preoperative CECT showing heterogenous lesion in the left moiety of horseshoekidney (1A), and a similar lesion arising from the right ovary in the pelvis (1B)



Figure2. Histologic (H&E) findings of primary neuroendocrine tumor arising within the horseshoe kidney. Original magnification ×200.



Figure 3. Positive IHC staining in the tumor cells, for Chromogranin (3A), Synaptophysin (3B), EMA (3C) and Neuron Specific Enolase (3D).



Figure 4. CECT Abdomen and Pelvis showing the recurrent tumor at the site of the primary

DISCUSSION

First described by, Resnick[3] in 1966, primary neuroendocrine tumors of the kidney are among the rarest of all renal neoplasms. They are thought to arise from enterochromaffin cells or amine precursor uptake and decarboxylation (APUD) cells, which are widely distributed throughout the body. In the urogenital tract, APUD cells have been described in the urinary bladder (especially in the region of the trigone), the prostate, the urethra, and the renal pelvis, but not in the renal parenchyma[4,5].

Only about 60 cases of primary neuroendocrine of the kidney have been reported in the international medical literature[6,7]. Although they exhibit morphologic and immunohistochemical features consistent with a hindgut neuroendocrine phenotype,[8] the precise histogenesis of renal neuroendocrine tumors is uncertain and is a matter of speculation. The most popular hypothesis is that primary renal neuroendocrine tumors arise from multipotential primitive stem cells capable of neuroendocrine differentiation[5,6].

The relative risk of presentation of primary neuroendocrine tumors in horseshoe kidney is inordinately greater to that of general population and has been reported as 62-82%[2,8]. The relative risk of developing renal neuroendocrine tumor in a horseshoe kidney is markedly greater than that for developing Wilms tumor or renal cell carcinoma in the same. Hence, this diagnosis must be suspected in patients with horseshoe kidney, especially if the tumor is located in the renal isthmus[9]. Horseshoe kidneys have been proposed to be the result of teratogenic factors, which may also account for the increased risk of malignant tumors in horseshoe kidneys[2,8].

The clinical course of renal neuroendocrine tumors is highly variable,[10] but in general most authors attest to their indolent nature[1,2]. Reports have described limited resection of the primary, and even resection of primary in presence of metastases, resulting in 3 year plus survival[1,11].

To the best of the author’s knowledge, no case of a primary neuroendocrine tumor of a horseshoe kidney presenting concomitantly with metastases to the ovary has been reported to date. The fact that the patient succumbed to symptomatic brain metastases within one year of having undergone an apparently curative surgery and adjuvant chemotherapy, points towards the aggressive nature of this disease.The reports bring forth a rare entity of primary neuroendocrine tumor in a horse shoe kidney. Though generally considered indolent tumors, the neuroendocrine tumor in our case exhibited aggressive nature as it presented with concomitant ovarian metastases, and later developed brain metastases within one year of radical curative therapy. The report high lights the fact that a very high index of suspicion for a neuroendocrine tumor needs to be aroused particularly when confronted with a tumor in a horseshoe kidney moiety.

References