Abstract

Ewing's sarcoma (SE) / primitive neuroectodermal tumor (PNET) occurs most often in soft tissues of the extremities and in the paravertebral areas. As far as we know, there are only two other reports in the gallbladder SE / PNET literature, however, this is the first metastatic case in a 58-year-old man. Microscopically, small round cell neoplasms showed intense positive immunoreactive activity for CD99, as well as for neuron-specific enoase and synaphysophine. The diagnosis of PNET was made based on the characteristic morphology and immunohistochemical findings, with the presence of t (11; 22) (q24; q12) - positive FLI1 chromosomal translocations.

 

Introduction

Ewing's sarcoma (SE) and primitive neuroectodermal tumor (PNET) are part of the family of Ewing's sarcoma tumors^1,2. They are considered primary malignant tumors of small round cells of bone and soft tissue¹. SE and PNET should be seen as two variants of the same tumor that differ only in their degree of neuronal differentiation, since they share an identical chromosomal translocation². Tumors that demonstrate neuronal differentiation are considered PNETs, ​​and those that are not differentiated are diagnosed as SE³. The Ewing sarcoma family of tumors occurs most commonly in soft tissues of the extremities and in the paravertebral areas. Extra-skeletal ES occurs more frequently in patients under 30 years of age, while PNET occurs more in patients over 40 years of age^2,4. ES and PNETs have already been reported in unusual places such as skin, soft tissues and viscera, for example, the pancreas^1,3. In this report, we present a case of primary SE / PNET in the gallbladder with hepatic metastasis diagnosed from immunohistochemical findings. It is a rare, metastatic finding in the gallbladder in adults.

 

Case report

Male patient, 58 years old, without comorbidities, smoker (> 50 pack / year), came to the general surgery service of Hospital São Vicente de Paulo (Passo Fundo- Brazil) with abdominal pain in the right hypochondrium for a month and a half. He reported in the consultation asthenia, anorexia, nausea, jaundice and weight loss of 10 kg without alteration in the diet. On physical abdominal examination, a palpable mass was identified in a hardened liver topography and a negative Murphy maneuver. For evaluation, the medical team requested laboratory tests which identified hypercalcemia, an increase in canalicular enzymes and a slight increase in liver enzymes. Tumor markers CEA (4.8ng/mL) and CA 19.9 (36 U/mL) within normal limits. The medical team requested a CT scan of the abdomen that showed the liver with preserved dimensions and heterogeneous density. In the topography of segment IV, in a just-hilar situation, it presented a voluminous hypodense, lobulated, heterogeneous mass, measuring 8.5 x 8.4 cm, with heterogeneous contrast impregnation and diffuse gallbladder parietal thickening (1.6 cm It still had material compatible with cholelithiasis and in combination, several hypodense nodular formations, with solid density, diffusely arranged along the hepatic parenchyma.The peripheral contrast impregnation, especially arterial, suggested secondary neoplastic implants in the topographies of segments III (1.9 x 1.8 cm), II (2.0 x 1.3 cm) and VI (1.2 x 1.2 cm). Based on the exams, the hospital's general surgery medical team suspected gallbladder neoplasia Continuing with the investigation, he performed a liver biopsy which showed round cell neoplasia (Image A), and in the immunohistochemistry exam, diffuse vimentin, multifocal synaptophysin, focal CD99 and multifocal FLI-1 were found (Image B). the patient quickly evolved to a severe condition of paraneoplasic hypercalcemia and subsequent death before the diagnosis was confirmed and treatment started.

 

 

Discussion

Primary extra-skeletal SE / PNETs are extremely rare and have been reported more frequently in the kidney^2,4. There are reports of primary SE / PNETs in the gallbladder, but this case differs from the others in that it is a primary tumor with the presence of multiple liver metastases^4,5. Another interesting factor in this case is the patient's age (58 years), since SE / PNET is more common among children and young adults^4,6,7.

The main risk factors for SE would be age, which is more common in adolescents, males ^4,8. Although the patient is male, what makes the case interesting is the discovery of SE / PNET in a 58-year-old adult, and this condition is extremely rare.

The pathological diagnosis of ES / PNET is based on histology and immunohistochemistry (the gold standard) and can be problematic due to the rarity of these tumors and the absence of a typical location⁶. In this report, biopsy and immunohistochemistry were essential for the diagnosis because the family of small round cell tumors is large and includes many different neoplasms^5,7. The expression coexistence of CD99 with positive expression of NSE or synaptophysin is sufficient for the diagnosis of ES / PNET⁸. The reported case presents diffuse vimentin, multifocal synaptophysin and focal CD99, in addition to negative immunohistochemical reactions (for example, ACL and S100) that rule out other neoplasms of the family of small round cell tumors^5,8.

The expression of multifocal FLI-1 conferring diagnostic certainty, since most Ewing / PNET sarcomas have a translocation involving the EWS gene on chromosome 22 and a gene encoding a transcriptional factor of the ETS family^8,9.

The treatment of EES / PNET generally includes multimodal chemotherapy combined with aggressive surgical treatment or radiation therapy ^7,10. Unfortunately, the patient died due to complications of paraneoplasic syndrome before the diagnosis was completed, preventing treatment combined with surgery and multimodal chemotherapy.

 

Conclusion

Although tumors of the Sarcoma Ewing family correspond to approximately 6% to 10% of primary malignant bone tumors and follow osteosarcoma as the second most common group of bone sarcomas in children, reports of extra-skeletal SE / PNETs are rarely reported^{1,4 ,10}. Currently, there is no research in the area for adults with this pathology. As far as we know, this case is only the third reported case of SE / PNET in the gallbladder, the first being metastatic.

 

References

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