A 62-year-old post-menopausal lady, without any previous co-morbidity, presented to our hospital with acute urinary retention, antecedent history of obstructive lower urinary tract symptoms, and occasional mild initial hematuria for the last 3 months. History of undocumented weight loss and loss of appetite was also present. The abdominal examination was normal. Per vaginal and speculum examination revealed a large mildly tender mass with a soft bluish tinge in the distal third of the vagina that was stretching the external urethral meatus. The mass extended across the entire length of the urethra and the overlying mucosa was normal. There was no bleed to touch or pus discharge. A catheter was placed to relieve the urinary retention and drained clear urine (Fig. 1a).
Multiphasic computed tomography (CT) scan of the abdomen and pelvis (Fig. 1b) showed 43 × 50 mm mass in the urethra bulging into the lumen of the urinary bladder along with bilateral hydroureteronephrosis. Hypodense lesions were also seen in segments IIa, III, V, and VI of the liver with the largest lesion (41 × 40 mm) present in the left lobe. Positron emission tomography (PET) CT scan (Fig. 1c and d) confirmed urethral mass, multiple large liver metastatic lesions, and additionally showed multiple enlarged cervical, supraclavicular, paratracheal, subcarinal, anterior diaphragmatic, internal mammary, retrosternal, and bilateral inguinal lymph nodes with increased tracer uptake. In addition, FDG avid paraaortic, aortocaval, paracaval, retrocaval, and mesenteric lymph nodes were also noted. The pancreas appeared bulky with nodular lesions and foci of increased uptake. Cystourethroscopy revealed a mass effect involving the whole length of the urethra. Urethral mucosa, urinary bladder, and bilateral ureteric orifices were normal. A trucut biopsy was taken from the urethral mass.
Histopathological examination showed a tumor with solid sheet pattern with few intervening small blood vessels (Fig. 2a-c). The tumor was composed of small cells with scant pale cytoplasm and ill-defined cell borders, high nucleo-cytoplasmic ratio, and moderate nuclear pleomorphism. Focally, nuclear molding and smudging were also identified. Frequent apoptoses and mitoses including atypical forms were appreciated (Fig. 2d). Some of these cells showed conspicuous eosinophilic nucleoli at places and the presence of melanin pigment in the cytoplasm which was highlighted on Fontana-Masson stain (Fig. 3a). As it was a trucut biopsy of mass, overlying mucosa was not included in the section to comment upon the junctional activity. A panel of immunohistochemical stains (Fig. 3b-f) were performed which demonstrated tumor cell immunopositivity for HMB-45 (1:250 dilution, mouse monoclonal antibody, clone HMB-45, Bio-SB, USA), Melan-A (1:250 dilution, mouse monoclonal antibody, clone A103, Bio-SB, USA), S-100 (1:400 dilution, rabbit polyclonal antibody, Dako, USA), synaptophysin (1:250 dilution, rabbit monoclonal antibody, clone EP158, Bio-SB, USA), chromogranin (1:200 dilution, mouse monoclonal antibody, clone LK2H10, SycTek, USA), and CD56 (1:200 dilution, mouse monoclonal antibody, clone 123C3.D5, Bio-SB, USA) while the tumor cells were negative for pancytokeratin (1:200 dilution, mouse monoclonal antibody, clone A1A3, SycTek, USA) and LCA (1:500 dilution, mouse monoclonal antibody, clone 2B11 & PD7/26, Bio-SB, USA). A final pathological diagnosis of malignant melanoma with neuroendocrine differentiation was rendered. Subsequently, a biopsy from the liver lesion was also carried out which displayed tumor with similar morphological features. Electron microscopic examination was performed in our institute using paraffin-embedded tissue material. One to two millimeter of tissue was deparaffinized in xylene followed by graded alcohol series and was immersed in 2.5% glutaraldehyde overnight. After buffer wash, secondary fixation in 1% osmium tetroxide for 2 h at 4 °C was done, again followed by washing in buffer to remove excess fixative. Dehydration was performed by passing the tissue through increasing concentrations of alcohol. After dehydration, the tissue was infiltrated and embedded using epoxy resin. Polymerization was achieved by keeping the embedded blocks at 50-60 °C for 12-24 h. Ultrathin sections were then cut and stained by uranyl acetate and lead citrate. Ultrastructural examination revealed the presence of both melanosomes (Fig. 4a) and neurosecretory granules (Fig. 4b) in the tumor cells further confirming the pathological diagnosis. No skin lesions were found on re-examining the patient following this diagnosis, before labeling it as primary urethral MM with neuroendocrine differentiation. The patient was started on palliative (dacarbazine based) chemotherapy due to lack of feasibility of immunotherapy. Later, the patient defaulted treatment and was lost to follow-up.