Renal neuroendocrine tumour with preoperative diagnostic dilemma

Description

A postmenopausal female in her 50s presented with left flank pain associated with fever and dysuria for 3 months. She had suffered from pulmonary tuberculosis 4 years ago for which she had received antitubercular therapy. On ultrasonography, there was marked thinning of left renal parenchyma at the upper pole with gross upper pole calyectasia and 6.7×5.4 × 5.7 cm mass at the lower pole of left kidney. Contrast Enhanced Computed Tomography (CECT) abdomen and pelvis with CT urography were suggestive of marked thinning of left renal parenchyma at the upper pole with ill-defined enhancing reniform heterogeneous mass at the middle and lower pole. There was no contrast excretion in the left pelvicalyceal system (figure 1). Based on the clinical presentation, differential diagnosis of xanthogranulomatous pyelonephritis, renal tuberculosis or renal cell carcinoma were considered. Metastatic workup ruled out any metastasis. Urine for acid-fast bacilli and TB-PCR were negative. A diethylenetriamine pentaacetate scan confirmed left kidney as nonfunctional. The patient underwent left laparoscopic radical nephrectomy. On the cut section, the upper pole of kidney was hydronephrotic with multiple pus-filled cavities with no residual normal parenchyma, while the mid and lower poles of the kidney were present with a mass lesion with no lymph node at the renal hilum. Histopathology was suggestive of a well-differentiated neuroendocrine tumour (grade 1) based on finding of tumour disposed in trabeculae, ribbons and glands. Tumour cells were mildly pleomorphic with round to ovoid nuclei, fine stippled chromatin, inconspicuous nucleoli and scant cytoplasm with eosinophilic trabeculae intermixed with nests of small, monotonous and cuboidal tumour cells. Cells undergoing mitosis were scarcely present. Immunohistochemistry showed strong cytoplasmic labelling for chromogranin and synaptophysin which confirmed the diagnosis (figure 2). At 1 month postoperatively, somatostatin receptor scintigraphy with 111-indium-labelled octreotide was done and it ruled out any metastasis or other site of occult disease.

Figure 1.

CECT abdomen and pelvis with urography showing in transverse sections (a, c and d) and coronal sections (b) marked thinning of left renal parenchyma at the upper pole with ill-defined enhancing reniform heterogenous mass at the middle and lower pole showing no excretion of contrast in left pelvicalyceal system.

Figure 2.

Gross specimen (a) showing hydronephrotic upper pole of kidney and mid and lower pole of kidney involved by a mass lesion with no lymph node present at the renal hilum and histopathology (b) suggestive of well-differentiated neuroendocrine tumour (grade 1) based on tumour disposed in trabeculae, ribbons and glands; immunohistochemistry (c and d) showing strong cytoplasmic labelling for chromogranin and synaptophysin.

The patient is under follow-up for the last 1 year without any recurrence.

Neuroendocrine tumours of kidney are rare with sparsely reported cases in the literature.^1–3 They are postulated to originate from renal stem cells that develop towards neuroendocrine differentiation, as there are no native neuroendocrine cells in adult renal parenchyma.² Due to the rarity of these lesions, the clinical presentation is still largely undetermined and poses a diagnostic challenge. Peak incidence has been reported in the fifth and sixth decades. The majority of the patients are asymptomatic but a small subpopulation (12.8%) of patients present with flushing, dyspepsia and diarrhoea that is, carcinoid syndrome, which were not present in our patient.⁴ However, if the patient is exhibiting any of the symptoms, then serum chromogranin and 5-Hydroxyindoleactic Acid (5 HIAA) should be done. Once the initial diagnosis is established octreotide scintigraphy is recommended to assess disease activity along with CT/MRI to rule out any nodal and distant metastasis.⁴ However, somatostatin receptor PET, including 68Ga-DOTATATE, 68Ga-DOTATOC or 64Cu-DOTATATE, has shown superiority to ¹¹¹In-pentetreotide scanning for the staging of neuroendocrine tumours; the NCCN guidelines recommend it for functional imaging along with anatomical imaging with CT or MRI.^{5 6} Radiologically on CT there is no or minimal enhancement of tumour, heterogeneity, and calcifications, which make it difficult to distinguish from renal cell carcinoma (RCC).⁴ They are unilateral, solitary and usually well circumscribed but rarely they are diffuse, necrotic and multiloculated with haemorrhagic friable cut surface (mimicking RCC). Neuroendocrine tumours may be differentiated from clear cell RCC (ccRCC) by strong positivity of chromogranin A and synaptophysin in renal neuroendocrine tumours.^{7 8} Recently, it has been postulated that the cell of origin of ccRCC is uncertain. In a recent study, all ccRCC expressed erythropoietin as well as neuron-specific enolase (NSE), which has traditionally been considered a neuroendocrine marker,⁹ which also indicates erythropoietin producing cells being the cell of origin of RCC. In another study, NSE expression was highest among tumours of neuroendocrine origin and ccRCC.¹⁰ Thus ccRCC may be a neuroendocrine tumour too, however, the nomenclature and classification of ccRCC remain yet to be modified.¹¹

The treatment protocol is not standardised with a range of available treatment options depending on grade and subtype.¹² However, surgical excision along with lymphadenectomy is often curative in the majority of the well-differentiated tumours. Some may require multimodality treatment (cisplatin-based chemotherapy, radiotherapy and transarterial chemotherapy for liver metastasis).¹² Our patient did not require any additional therapy and was tumour free at 1 year of follow-up.

Patient’s perspective.

• When I came to the hospital in pain with fever, I initially thought I might be having kidney stones. But, after investigations, I was told by my doctor that I have a mass in my left kidney for which the doctors were not very sure of what it is. But they told me that it might have high chances of malignancy and the left kidney is non-functional as well. So they advised that I should go for left kidney removal by laparoscopic approach for which I consented. After the surgery pain gradually decreased and then after the biopsy report came, I was told that I had a rare tumour of the kidney and on further scanning, thankfully the tumour was not present at any other site. It has been 1 year (post-surgery) and I have been regularly visiting my doctor for follow-up, till now no recurrence has come up, but I’m a bit anxious too.

Learning points.

• Renal neuroendocrine tumour is a rare tumour, thus most of the time it is diagnosed postoperatively in retrospect.

• In case of any of the suspicious symptoms or doubtful findings on axial imaging, a high index of suspicion should be kept. If the patient is diagnosed postoperatively on histopathology, then somatostatin receptor PET study can be done to rule out any occult disease.

• Appropriate treatment depends on the exact histopathology and stage of the disease. Follow-up protocol is not well defined in the literature, so it has to be individualised.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).