Yasmin S. Hamirani, MBBS; Evangeline Ndigwe, MS; Suvarchala Kompella, MD; Heather Mannuel, MD; Kris Shekitka, MD; Jeffrey Siebel, MD; and Jesus Esquivel, MD, St. Agnes Hospital, Baltimore, MD
Yasmin S. Hamirani, MBBS
Department of Internal Medicine
Evangeline Ndigwe, MS
Medical Student III
Department of Internal Medicine
Suvarchala Kompella, MD
Department of Internal Medicine
Heather Mannuel, MD
Department of Medical Oncology
Kris Shekitka, MD
Department of Pathology
Jeffrey Siebel, MD
Department of Pathology
Jesus Esquivel, MD
Department of Surgical Oncology
St. Agnes Hospital
Introduction: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignancy. Peritoneal involvement by this tumor is rare. The differential diagnosis of EHE includes malignant mesothelioma of the peritoneum, primary peritoneal carcinoma, and peritoneal carcinomatosis (metastatic carcinoma).
Results and discussion: The authors report the case of a middle-aged African American man with persistent abdominal pain and a normal initial diagnostic workup. Laparotomy and histologic examination of the omentum confirmed the diagnosis of EHE. Complete resection was not possible because the tumor was widespread throughout the abdominal cavity.
Conclusion: EHE remains a diagnostic dilemma due to its nonspecific features. The survival rate is low because the tumor is often diagnosed at a late stage, especially when it originates from the peritoneum or small intestine.
Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor that is difficult to diagnose because of its nonspecific presenting symptoms. Only 12 cases of EHE have been described in the literature. Although the tumor has been encountered in all age groups, it usually presents in the fourth through seventh decades of life. We report the case of a middle-aged man who presented with abdominal pain. Following an omental biopsy, EHE of the peritoneum was diagnosed. Complete resection was not possible because the lesion had spread throughout his abdomen.
A 47-year-old African American man with no comorbid conditions had experienced severe generalized abdominal pain, predominantly on the right side, for 6 weeks. Although the pain was persistent, it was relieved slightly when he was in the left lateral decubitus position. He also experienced nausea, vomiting, anorexia, alternating diarrhea and constipation, and a 10-lb weight loss. He had no fever or urinary symptoms and no recent history of travel, exposure to chemicals, or surgery. His social history was significant for smoking 5 cigarettes daily for 12 years. There were no significant illnesses in his family history.
Physical examination showed a rigid, distended abdomen that was diffusely tender to palpation. Hypoactive bowel sounds were detected on auscultation. No lymphadenopathy was identified.
Laboratory studies showed a normal white blood cell count, with monocytosis and a mildly increased erythrocyte sedimentation rate. His amylase and aspartate aminotransferase levels were normal. Results of a human immunodeficiency virus test, hepatitis screens, and a hepatobiliary iminodiacetic acid (HIDA) scan for cholecystitis were negative. Abdominal radiographs showed a paucity of bowel gas, suggesting fluid-filled bowel loops. Colonoscopy revealed no abnormalities, and a biopsy demonstrated only focal nonspecific cryptitis. A computed tomography (CT) scan of the abdomen found a 2.3-cm heterogenous cyst in the tip of right lobe of the liver, thickened loops of small bowel in the right lower quadrant, and ascites (Figure 1). A small bowel series showed thickening and narrowing of the small bowel (especially the terminal ileum), consistent with inflammatory bowel disease (Figure 2). Treatment of suspected Crohn's disease was initiated with 5-aminosalicylic acid (Asacol, Pentasa, Rowasa), metronidazole (Flagyl), ciprofloxacin (Cipro), and methylprednisolone (Solu-Medrol), but no improvement was noted. Total parenteral nutrition was started. Results of a diagnostic workup for the liver cyst were negative for antibody. Results of a tagged red blood cell scan were negative for hemangioma, and a fine-needle aspiration biopsy showed benign liver tissue.
Considering the patient's unchanged clinical condition, exploratory laparotomy was performed, which showed diffuse mesenteric involvement of malignant epithelioid cells and ascitic fluid. On discovery of diffuse peritoneal disease, a biopsy was performed and the abdomen was closed without further intervention. The patient was discharged to a hospice facility for comfort care, where he received intravenous morphine and hydromorphone (Dilaudid) for pain control.
Results of the omental biopsy were positive for EHE, confirmed by strong positive immunohistochemical staining for vimentin, CD31, and CD34. These immunostains are markers for endothelial differentiation. Microscopic examination revealed infiltrating cords of plump epithelioid cells involving the omentum. Closer examination of these cells showed clear cytoplasmic vacuoles, consistent with intracytoplasmic vascular lumen (Figure 3).
Only 1% of all cancers are vascular. These lesions have indolent growth patterns and sometimes go into remission on their own, whereas others recur and are locally destructive. (HE) is used to describe a group of vascular tumors of intermediate malignancy that usually involve soft tissue but can also involve the liver, lungs, skin, lymph nodes, and bones.1,2 There are four recognized subgroups of HE: epithelioid (EHE), spindle cell, kaposiform, and malignant endovascular papillary angioendothelioma (Dabska tumor).3
EHE typically displays indolent behavior and has a propensity for multifocal involvement. Only 12 cases of primary peritoneal EHE have been described in the liter-ature.4-12 Peritoneal carcinomatosis, primary peritoneal carcinoma, and malignant peritoneal mesothelioma are included in the differential diagnosis of these tumors.6
Most cases of EHE occur when patients are between their fourth and seventh decades of life, but a range in age between 11 and 77 years has been reported.13 Although EHE has an equal sex distribution, involvement of the lungs and liver is more frequently observed in women.13
EHE constitutes fewer than 3% of all small intestinal tumors (predominantly jejunal and ileal). Only 7 cases of EHE of the small intestine have been reported.14-20 Laparotomy and histopathologic examination are currently the only means to diagnose EHE. In the absence of a discrete abdominal mass, EHE has no definitive diagnostic features on radio-logic examination. Our patient's two successive abdominal CT images showed only thickening of the small bowel loops. At laparotomy, the diffuse peritoneal involvement of his EHE made it difficult to identify the small intestine or peritoneum as the primary site of origin.
EHE carries a grave prognosis. It has an overall mortality rate of about 13%, but this can be as high as 65% for patients whose tumors arise in the liver.5 The 5-year survival rate for patients with EHE is only 33.5%, mainly because the condition is often diagnosed late.14
EHE generally displays a lobular architecture consisting of cords and strands of primitive-appearing epithelioid cells with intracytoplasmic lumina, occasionally containing red blood cells. The cytoplasm of the tumor cells can be bimorphic, containing eosinophiles that range from abundant and pale to clear and vacuolated. The neoplastic endothelial cells usually show mild nuclear atypia and infrequent mi-totic figures without atypical mitoses.4 Most cases of EHE test positive for CD34, CD31, and factor VIII immunostains.
In contrast to EHE, epithelioid angiosarcoma is a mitotically active and highly atypical neoplasm. Immunohistochemical evaluation is the best way to distinguish primary EHE of the peritoneum or the small intestine from malignant mesothelioma and carcinomas. Some vascular tumors, including EHE, can stain positive for epithelial markers (eg, epithelial membrane antigen and some cytokeratins), so the use of endothelial markers CD31, CD34, and factor VIII can prove helpful in problematic cases. Electron microscopy demonstration of Weibel-Palade bodies can also confirm the vascular origin of these tumors when light microscopic features and immunohistologic findings are inconclusive or ambiguous.6
Only 1 of the 12 reported cases mentions performing CT examination of this tumor, which revealed a diffuse peritoneal fluid collection and multiple confluent masses arising from the peritoneum. These masses contained multiple enhanced nodules on arterial phase, with delayed filling of the entire masses on equilibrium phase.5 This radiographic feature was not observed in our patient's case.
EHE remains a diagnostic dilemma because of its nonspecific presenting features. Currently, this rare tumor has eluded early diagnosis when presenting in the peritoneum or small intestine. Laparotomy followed by histopathology evaluation with immunohistochemical staining is currently the only means of making a definitive diagnosis.
The authors have no relationship with any commercial entity that might represent a conflict of interest with the content of this article and attest that the data meet the requirements for informed consent and for the Institutional Review Boards.