Metastatic Perivascular Epithelioid Cell Tumor of the Colon in a Child

Painless hematochezia in a school-age child is the hallmark of a juvenile colorectal polyp. Rarely do malignant gastrointestinal (GI) neoplasms present with painless rectal bleeding in childhood. We describe the clinical and pathological features of a PEComa of the sigmoid colon with regional metastases in an 11-year-old boy with painless hematochezia and mild anemia. The PEComa is a recently described tumor of unknown cellular origin and low-grade malignancy characterized by both smooth muscle and melanocytic differentiation. Most cases affect adult women, and most tumors are found in the uterus (1). To the best of our knowledge, this is the first report of a metastatic PEComa involving the GI tract of a child. CASE REPORT A previously healthy 11-year-old prepubertal white boy was referred to a pediatric gastroenterologist with a 5-month history of intermittent painless rectal bleeding. There was no history of bleeding disorders, recent infection, change in bowel habits, or significant weight loss. The family history was significant for colonic polyps in his maternal great-grandmother. On digital rectal exam, there was some gross blood mixed with soft stool. Hematocrit was 30%, and mean corpuscular volume was 72 fL. A Meckel scan was negative. Lower endoscopy revealed a sessile polypoid mass approximately 3 cm in diameter in the sigmoid colon. Repeated attempts at endoscopic removal resulted in profuse bleeding, requiring blood transfusions. Histopathological examination of the resected tissue, although nondefinitive, suggested a malignancy, possibly malignant melanoma, alveolar soft part sarcoma, or PEComa. Three weeks later, the patient was seen at Children's Hospital of New Orleans for further evaluation. At this time, he was asymptomatic, and the results of his physical examination were normal. Hemoglobin and hematocrit, chemistry panel with liver function tests, uric acid, lactate dehydrogenase, and erythrocyte sedimentation rate were normal. Computed tomography (CT) scans of the chest, abdomen, and pelvis were negative for masses. Colonoscopy revealed a sessile polypoid mass with irregular surface in the sigmoid colon (Fig. 1). There was no active bleeding. The surrounding mucosa and the rest of the colon had a grossly normal appearance. The patient subsequently underwent surgical resection of a 5.5-cm length of sigmoid colon, including the mass, with primary anastomosis.FIG. 1: Endoscopic view of sigmoid colon showing the single sessile, polypoid mass with irregular surface and normal surrounding mucosa.Examination of the resected colon revealed a 1.2- × 1.0- × 0.7- cm tan, firm, and sessile nodule on the antimesenteric aspect of the colon. Microscopically, the epicenter was the muscularis mucosae. The overlying mucosa was infiltrated and ulcerated, and the tumor extended through the muscularis propria into the subserosal tissue with lymphatic invasion. Numerous islands of neoplastic cells surrounded by fibrovascular septa had abundant clear to granular cytoplasm, with no pigment (Fig. 2A). The nuclei were uniform in size, round, and vesicular, with uneven distribution of chromatin and centrally placed, large, prominent nucleoli. Reticulin surrounded groups of cells, not individual ones. Occasional mitoses including tripolar mitoses and tissue necrosis were present, indicative of malignant potential. Diastase-resistant periodic acid–Schiff—positive intracytoplasmic crystals (characteristic of alveolar soft part sarcoma) were not present. Immunostains demonstrated diffuse cytoplasmic positivity for anti-human melanoma black 45 (HMB45), but S-100 and cytokeratin were negative. Desmin and smooth muscle actin were positive in the prominent vessels but not the clear cells. The surrounding colonic mucosa, submucosa, and muscularis propria were normal, with normal ganglion cells present. Two of 7 accompanying serosal lymph nodes contained metastatic tumor, distending the subcapsular sinus (Fig. 2B). All of the surgical margins were free of tumor.FIG. 2: A, Tumor cells with abundant clear to granular cytoplasm, with uniform round nuclei and centrally placed large prominent nucleoli. Cells are arranged in islands surrounded by fibrovascular septa (hematoxylin and eosin, ×100). B, Two of 7 resected regional lymph nodes contain metastatic tumor, distending the subcapsular sinus (hematoxylin and eosin, ×20). C, Transmission electron microscopy showing smooth muscle differentiation with intermediate filaments and dense bodies (DB) (×2100). D, Premelanosomes (M) (×6600).Electron microscopy revealed collections of intermediate filaments with dense bodies under the plasma membrane, suggesting smooth muscle differentiation (Fig. 2C). In the cytoplasm, there were premelanosomes with tubuloreticular interiors (Fig. 2D). On the basis of the histopathological findings, the diagnosis was low-grade malignant metastatic colonic PEComa. The patient did well postoperatively; 5 months later, he continues to be asymptomatic with normal CT scans of the abdomen and pelvis. Upon recommendation of the local tumor board and an extensive search of the available medical literature, no additional treatment was given, and plans are to see the patient every 6 months for cancer surveillance with history, physical examination, and CT scans. In addition, a yearly colonoscopy will be performed to rule out local recurrence of the tumor. DISCUSSION The term “PEComa” was first coined in 1996 (2) to describe certain pancreatic, pulmonary, renal, and hepatic tumors showing perivascular epithelioid cell differentiation. In the past, these tumors have gone by various names, including clear cell myomelanocytic tumors, extrapulmonary sugar tumors, and clear cell tumors (3). In 2002 the World Health Organization accepted the designation “PEComas,” defining them as mesenchymal neoplasms that share the same distinctive cell type, the perivascular epithelioid cell (PEC) (4). This cell has no recognized normal cellular counterpart. Its key histological features are a large epithelioid appearance with abundant clear to granular eosinophilic cytoplasm and a large vesicular nucleus. As seen in our patient's tumor, these cells characteristically form nests or sheets surrounded by blood vessels. Another distinctive feature is that on both immunohistochemical and ultrastructural levels, PEComas have dual melanocytic and smooth muscle differentiation (1). PEComas are positive for HMB45, an antibody against melanosomes, and often positive for smooth muscle markers as well. In addition, ultrastructurally they reveal both premelanosomes and smooth muscle components. Although in our case, muscle stains such as desmin and smooth muscle actin were negative, electron microscopy of our patient's tumor did demonstrate smooth muscle differentiation along with premelanosomes, showing how both smooth muscle and melanosomes were expressed by the same tumor cell. The anti-HMB45 antibody reacts against an intracytoplasmic antigen present in immature melanosomes. By contrast, the S100 protein is an antigen normally found in cells derived from the neural crest (eg, Schwann cells, melanocytes, glial cells) but is not necessarily involved in melanosome production (1). In our case, reactivity to anti-HMB45 without reactivity to anti-S100, with the given histological appearance, was what has been described as a feature of PEComas rather than malignant melanoma. The fact that the PEComa is S100 negative suggests that the cell of origin is a non-neural crest melanosome-producing cell. It may be a smooth muscle cell that has acquired the ability to make melanosomes. The natural history of the PEComa is also distinct from that of a melanoma in that it is a low-grade malignancy. However, although most PEComas behave in a benign fashion, subsets of PEComas have been described with malignant clinical and histopathological features (1). Our patient's tumor exhibited some of these features, including prominent nucleoli, tripolar mitoses, tumor necrosis, and local invasiveness, with the proof of malignancy being the metastases to regional lymph nodes. The fact that PEComas have only recently been characterized may account for the relatively few reported pediatric cases. Our search of the English medical literature through PubMed, using the key words “perivascular epithelioid cell tumor” and “PEComa” resulted in 20 cases in children younger than 18 years old, only 3 of them involving the GI tract. The first case involved the rectum of a 9-year-old girl (5), the second was a duodenal PEComa found 8 years after treatment of a neuroblastoma in a 12-year-old boy (6), and the third involved the transverse colon of a 16-year-old girl (7). In contrast to our patient's tumor, none of these were found to be metastatic. Our case demonstrates that caution should be exercised when a large sessile polypoid mass is found in the colon of a child. Although endoscopic removal in a piecemeal fashion is practiced in adults (8), this approach can lead to severe bleeding complications. Moreover, such a mass is rarely seen in children and should immediately raise suspicion of an unusual malignancy (9). Inasmuch as complete endoscopic removal would not likely be successful, primary surgical excision with healthy tissue margins and removal of local lymph nodes may be the preferred approach. In fact, in our case, it was only after complete excision that the correct diagnosis could be established. Little is known about prognosis and treatment modalities for PEComas. Only case reports have been published (10–13). The use of chemotherapy and/or radiation has not always been effective, and several patients have done well with surgical resection alone. In view of the fact that PEComas are generally of low-grade malignancy and that the benefit of chemotherapy and/or radiation is not established, we decided to closely monitor our patient for tumor recurrence without additional therapy. However, more follow-up studies are needed to establish the wisdom of such a conservative approach.