Capillary hemangioblastoma, is a benign tumor which consists of a network of small blood vessels along with lipid-laden stromal cells.5 The stromal cells may exhibit significant nuclear pleomorphism, mimicking cancer tissues. It can occur either sporadically, or in association with VHL disease in around 25% of the patients.6 The common age of presentation is between 20 to 50 years with a male: female ratio of 2:1. This tumor most commonly occurs in the CNS, predominantly in the cerebellum, but can occasionally occur in the meninges, retina, spinal cord, corpus callosum, lateral ventricle, pituitary gland, and the optic nerve. Rarely, hemangioblastoma can be seen in other sites, such as retroperitoneum, skin, liver, pancreas, lung, adrenal, peripheral nerve, soft tissue, and urinary bladder, usually in association with VHL syndrome. VHL is an autosomal dominant syndrome associated with germline mutation in the VHL tumor suppresser gene located on chromosome 3p.7,8 There are only few reports on sporadic hemangioblastoma occurring outside the CNS, including kidney.9-14 Till date only 26 cases of sporadic RH have been reported. RH are asymptomatic masses generally found incidentally as in our case. Rarely, they may present with loin pain or haematuria.
MMT also known as uterine carcinosarcoma is a rare uterine malignancy occurring in postmenopausal females in 5th to 6th decade of life. It comprises of only 1–2% of all uterine neoplasms.15 It is a dedifferentiated and aggressive form of endometrial carcinoma having poor prognosis.16 They have high chances of metastasis commonly to the lung (49%), peritoneum (44%), pelvic or para-aortic lymph nodes (35%), adrenal gland or bone (19%), heart or pericardium (9%), and/or brain (7%). Other rare sites include the pancreas, liver, eye thyroid gland and skin.17 The clinical presentation of carcinosarcomas is nonspecific and is similar to other pelvic neoplasms. Patient may present with pyometra with vaginal bleeding, bloody or watery discharge, abdominal pain, or with a polypoid mass in a postmenopausal woman. A “symptom triad” has been defined favouring carcinosarcoma over endometrial adenocarcinoma which includes pain, severe vaginal bleeding, and the passage of necrotic tissue per vaginum. MMT doesn’t have pathognomonic appearance on MRI. However, there should be a suspicion of MMT in the presence of a large heterogenous infiltrative tumor or when tumor enhancement is equal to or greater than the myometrium. The diagnosis is made by doing endometrial sampling and HPE of the sample.
On HPE there are both epithelial and mesenchymal elements suggestive of MMT. PET scan useful to identify unsuspected disease, extra-pelvic site or rule out metastasis 18 , 19, 20 Surgical management should include extra fascial hysterectomy with bilateral salphingo-oophorectomy, infracolic omentectomy, bilateral pelvic and in some cases para-aortic lymphadenectomy.
Based on the GOG 161 study, Ifosfamide/ Paclitaxel is considered the treatment of choice21 and paclitaxel/carboplatin is equally effective 22 as adjuvant treatment and was used by our medical oncology team.23 There is increasing role of adjuvant chemo-radiation now with significant overall survival however multiple demographic and clinical factors influence the choice of adjuvant therapy.24, 25 Despite the use of aggressive therapy, only modest improvement in overall survival is noted over the last few decades with a five-year overall survival rate of approximately 20–30%.26
The occurrence of rare tumors like sporadic RH and MMT in the same patient is very rare entity. When a new tumor is found in a patient with one existing tumor we need to differentiate it from metastasis to determine the further management and prognosis. To differentiate, a combination of history, clinical, radiological and pathological investigation will be needed. The most appropriate way to distinguish is by HPE as it will show different cells of origin.
RCC needs to be differentiated from RH as the former is malignant and the latter is essentially benign. Each of them has a different prognosis and differentiating the two will help avoid over-diagnosis and unnecessary treatment.
- On radiology and gross examination, RH mimics various renal neoplasms. Clear cell variety of RCC shares various morphological features with RH, making it the most common differential diagnosis. Thus, RCC may occasionally have a hemangioblastoma-like pattern making it nearly impossible to distinguish it from RH on morphological basis. 27,28
- The clues to the diagnosis of RH are circumscribed borders, sheets of large polygonal cells with arborizing thin-walled blood vessels and pleomorphic nuclei, paucity of mitotic figures despite prominence of atypical cells. The presence of peri-cytomatous growth patterns and intracytoplasmic lipid vacuoles strongly suggests hemangioblastoma although both tumor types have similar morphological features, such as clear cytoplasm and a vascular network. 12,27,28
- To confirm the diagnosis of hemangioblastoma, IHC must be done. The absence of immunostaining for cytokeratin, and positive staining for α-inhibin, S100 and NSE is diagnostic of hemangioblastoma. 27,28
- Since they can be sporadic or associated with VHL syndrome a polymerase chain reaction sequencing analysis of the VHL gene is done to confirm presence of mutation in the
RH needs to be correctly diagnosed as sporadic RH does not require further treatment and it has a very good prognosis.14 Adjuvant therapy in MMT will depend on the histology of tumor in terms of local invasion, nodal status and adequacy of margins. Prognosis in case of MMT and RH depends on biological potential of MMT as RH is a benign condition.
Such cases need a multidisciplinary approach with a team of gynaecologists, onco-surgeons, urologist, radiologist, pathologist and medical oncologist. The key is to evaluate each tumor independently. They should be treated aggressively with the intent to cure each, so as to achieve maximum therapeutic benefit