DOI: https://doi.org/10.21203/rs.3.rs-53502/v1
Background: The differential diagnosis for a colonic submucosal tumor (SMT) can include many types of cancer. We report a case of a perivascular epithelioid cell tumor (PEComa), a rare mesenchymal neoplasm that demonstrates SMT morphology, in the ascending colon.
Case presentation: A mass was incidentally detected by computed tomography (CT) in a 53-year-old man. Colonoscopy revealed an SMT with central ulceration in the ascending colon, and 18F-fluoro-2-deoxy-D-glucose positron emission tomography CT demonstrated a high maximum standardized uptake value of 7.33. Preoperative diagnosis was inconclusive. Given the malignant potential of the tumor, we performed a laparoscopic right hemicolectomy with D3 lymph node dissection. The tumor was 5.5 cm × 4.1 cm and located in the submucosa and muscular propria. There was no lymph node metastasis (0/46). Based on the positive immunohistochemical stainings of both melanocytic (HMB45) and muscle (desmin) markers, we diagnosed the tumor as a PEComa. In the 17 months since surgical resection, the patient has not experienced recurrence, but careful observation should continue because of the malignant potential of the tumor.
Conclusions: Although rare, a PEComa should be considered in the differential diagnosis of colonic SMT. Immunohistochemical staining of melanocytic and muscle markers is useful for the diagnosis.
A colonic submucosal tumor (SMT) constitutes various differential diagnoses including gastrointestinal stromal tumor (GIST), neuroendocrine tumor, smooth muscle tumor, schwannoma, malignant lymphoma, and primary or metastatic colon cancer 1. We report a case of perivascular epithelioid cell tumor (PEComa) demonstrating SMT morphology in the ascending colon. PEComa is a rare mesenchymal neoplasm with a particular immunohistochemical profile3. We also summarize previous colonic PEComa cases and investigate their clinicopathological characteristics.
A 53-year-old man with cough and fever but no abdominal symptoms underwent computed tomography (CT), and a mass was incidentally discovered in the right intra-abdominal region. After referral to our hospital, a contrast-enhanced CT showed a 50 mm mass with heterogeneous enhancement (Fig. 1A) and a 10 mm regional lymph node (Fig. 1B). A subsequent colonoscopy showed an SMT with central ulceration in the ascending colon (Fig. 1C). 18F-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography CT demonstrated a high maximum standardized uptake value of 7.33 (Fig. 1D). A biopsy taken during the colonoscopy did not provide adequate tumor specimens for pathological investigation. Given the malignant potential of the tumor, we performed a laparoscopic right hemicolectomy with D3 lymph node dissection2.
Macroscopic examination revealed a 5.5 cm × 4.1 cm tumor located in the submucosa and muscular propria, protruding into the mucosal and serous surfaces (Figs. 2A and 2B). Central ulceration was confirmed, and the surgical resection margin was negative. There was no lymph node metastasis (0/46). Histopathological assessment of the tumor cells showed abundant clear cytoplasm and trabecular, nested architecture (Fig. 3A). The initial diagnosis was GIST, but immunohistochemical staining of CD117 was weak (Fig. 3B). Additional immunohistochemical staining of CD34 (Fig. 3C), S-100 (Fig. 3D), MyoD1 (Fig. 3E), and SMA (Fig. 3F) were negative; however, HMB45 (Fig. 3G) was strongly positive, and desmin (Fig. 3H) was partially positive. We diagnosed the tumor as a PEComa based on the co-expression of melanocytic (HMB45) and muscle (desmin) markers3. The histology of the specimen showed a high nuclear grade and cellularity, and the mitotic rate was zero. Both tumor necrosis and lymphovascular invasion were positive, and the Ki-67 index was 13% (Fig. 3I). There has been no tumor recurrence in the 17 months since the surgical resection.
PEComa is a rare mesenchymal neoplasm defined by the World Health Organization in 2002 as a “mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells” 4. As was seen in our case, a diagnosis can be made by melanocytic markers such as HMB-45 and Melan A and the muscle markers SMA and desmin.
The difficulty of obtaining a sufficient tumor sample makes the preoperative diagnosis of SMT challenging, particularly in the right-sided colon. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) has recently improved the ability to diagnose SMT; however, EUS-FNA for right-sided colon lesions is still technically complicated and not standardized5, 6. In our case, a biopsy taken during colonoscopy did not yield a sufficient tumor sample for preoperative diagnosis.
When a biopsy cannot be performed, images can determine the treatment strategy. In our case, the images indicated a potential malignancy according to guidelines presented in the literature7: a large tumor size (> 5 cm), heterogeneous enhancement in CT, high FDG accumulation, and central tumor ulceration. The discovery of a swollen 10 mm regional lymph node further suggested the possibility of malignancy. These findings provided compelling evidence to perform surgery for both diagnostic and therapeutic purposes, and we did a minimally invasive laparoscopic procedure to perform systematic tumor resection and lymph node dissection.
We did a literature search using PubMed to investigate the clinicopathological features of colonic PEComa and found 21 primary cases, including that of our patient8–24. These are summarized in Table 1. The median age was 36 years (range: 7–62 years), and the percentage of females was 61.9%, suggesting that the patients were predominantly younger and female, as reported in a recent systematic review of GI PEComa3. The tumors were found equally on both sides of the colon (right side: 11 cases and left side: 10 cases). The tumors were large (median: 4.8 cm, range: 1.2–10.0 cm), and most patients were symptomatic (85.7%). Preoperative diagnosis of colonic PEComa was difficult in most cases, and only one patient had a suspected PEComa from the specimen obtained under colonoscopy13. There was diversity in the extent of surgical resection and lymph node dissection, which could be explained by the difficulty of preoperative diagnosis.
| Year | Age / Sex | Symptom | Site | Size (cm) | Preoperative diagnosis of PEComa | Mitosis (/ 50 HPF) | Necrosis | LVI | Metastasis at diagnosis | Surgical treatment | Adjuvant therapy | Recurrence | Status | Follow-up (month) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 2004 8 | 35/ F | None | C | 4.0 | - | - | - | NS | - | Hemicolectomy | - | - | Alive | 3 |
| 2004 9 | 36/ F | Bleeding | C | 3.5 | - | < 5 | + | NS | - | Hemicolectomy | NS | NS | NS | NS |
| 2006 10 | 43/ F | Abdominal pain | D | 8.0 | - | 2 | - | + | - | Partial colectomy | - | PD | Dead | 38 |
| 2007 11 | 16/ F | Bleeding | T | 2.0 | - | 0 | - | NS | - | Partial colectomy | - | - | Alive | 24 |
| 2008 12 | 16/ F | Bleeding | T | 1.8 | NS | NS | - | - | - | Hemicolectomy | - | - | Alive | 41 |
| 2008 13 | 11/ M | Bleeding | S | 1.2 | Suspected | Occasional | Occasional | + | - | Partial colectomy | - | - | Alive | 5 |
| 2008 14 | 11/ M | Bleeding | D | 3.5 | - | Infrequent | Infrequent | NS | - | Partial colectomy | - | NS | NS | NS |
| 2009 15 | 43/ F | Abdominal pain, bleeding, diarrhea | C | 1.5 | - | < 3 | - | - | - | Hemicolectomy | - | NS | NS | NS |
| 2010 16 | 17/ F | Bleeding | S | 6.0 | - | Low | NS | NS | - | Sigmoidectomy | - | - | Alive | 180 |
| 2010 18 | 45/ F | Abdominal pain, bleeding | A | 3.5 | - | Low | - | NS | - | Partial colectomy | - | - | Alive | 36 |
| 2010 18 | 36/ M | Abdominal pain, bleeding | D | 4.8 | - | Low | NS | NS | - | Partial colectomy | - | - | Alive | 32 |
| 2010 18 | 42/ M | Abdominal pain, bleeding | S | 4.5 | - | 1 to 2 | - | NS | - | Partial colectomy | - | - | Alive | 15 |
| 2010 18 | 38/ F | Abdominal pain, bleeding | A | 6.0 | - | Low | - | NS | - | Partial colectomy | - | - | Alive | 8 |
| 2010 17 | 7/ M | Abdominal pain, bleeding | A | 4.0 | - | Low | - | - | - | Hemicolectomy | IFN-α | - | Alive | 26 |
| 2012 19 | 62/ F | Bleeding | S | 5.0 | - | NS | NS | NS | - | Anterior resection | - | - | Alive | 16 |
| 2012 20 | 62/ F | Abdominal pain, bleeding | S | 5.0 | - | 0 | - | NS | - | Partial colectomy | - | - | Alive | 4 |
| 2013 21 | 23/ M | Abdominal pain, bleeding | C | 5.5 | - | 60 | 60% | NS | LN, liver | Hemicolectomy, hepatectomy | Sirolimus | Local, liver | Dead | 23 |
| 2016 22 | 40/ M | Dyschezia | S | 7.0 | NS | 0 | - | - | - | Sigmoidectomy | - | Local, pancreas | Alive | 27 |
| 2016 23 | 42/ F | None | D | 5.0 | - | NS | NS | NS | - | Hemicolectomy | - | - | Alive | 5 |
| 2018 24 | 36/ F | Abdominal pain, bleeding | T | 10.0 | - | NS | NS | NS | - | Partial colectomy | NS | NS | NS | NS |
| Our case | 53/ M | None | A | 5.5 | - | 0 | + | + | - | Hemicolectomy | - | - | Alive | 17 |
| F, female; M, male; C, cecum; A, ascending colon; T, transverse colon; D, descending colon; S, sigmoid colon; NS, not specified; LVI, lymphovascular invasion; LN, lymph node; IFN, interferon; PD, peritoneal dissemination | ||||||||||||||
Forpe et al. proposed guidelines for malignant potential in GI PEComa: >5 cm, infiltrative, high nuclear grade and cellularity, mitotic rate > 1/50 HPF, necrosis, and vascular invasion25. One patient with a large tumor (5.5 cm), high mitotic rate (60/50 high-power fields), and 60% tumor necrosis had lymph node and liver metastases at initial diagnosis21. Our patient has not experienced recurrence during the 17 months after surgery, although we had concerns because he met five of Forpe’s six criteria to predict malignancy. Follow-up should be continued because information regarding disease pathology and prognosis is limited. More cases with longer follow-up periods are needed to predict the prognosis of colonic PEComa, although this will be difficult because of the rarity of the tumor.
In conclusion, PEComa, although rare, should be considered in the differential diagnosis of colonic SMT. Immunohistochemical staining of melanocytic and muscle markers is useful for the diagnosis, although preoperative diagnosis is difficult. Image findings could indicate a malignant potential. More research and case reports are needed to provide guidance for effective PEComa surgery and long-term care.
SMT, submucosal tumor; GIST, gastrointestinal stromal tumor; PEComa, perivascular epithelioid cell tumor; CT, computed tomography; FDG, fluoro-2-deoxy-D-glucose; EUS-FNA, Endoscopic ultrasound-guided fine-needle aspiration.
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Written informed consent was obtained from the patient to publish this case report.
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The authors have no competing interests to declare.
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YN and KT made study conception and design. AK performed the histological examination. AK, YG, KO and KD participated in the patient’s surgical treatment. YN is the major contributor in writing the manuscript. All authors read and approved the final manuscript.
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