A Case of Colon Leiomyosarcoma Arising from the Muscularis Mucosae: A Case Report and Literature Review

Abstract

INTRODUCTION: Colon leiomyosarcoma (CLMS) is an extremely rare neoplasm and the information regarding its clinical characteristics and specific treatment was still unclear.

CASE PRESENTATION: A 73-year-old female who had been diagnosed with transverse CLMS underwent laparoscopic surgery. The resected specimen showed that the tumor contained proliferation of spindle-shaped cells and arranged in fascicular pattern, which was immunohistochemically positive for smooth muscle actin and desmin. Moreover, the tumor bottom was not continuous with the muscularis propria and had a clear border in the submucosa layer. According to these findings, we finally diagnosed it as primary CLMS arising from the muscularis mucosa (MM). No recurrence was noted 24 months after surgery.

CONCLUSIONS: This literature demonstrates CLMS arising from MM and suggests that its pathological diagnosis is associated with disease prognosis.

Abbreviations

CLMS

colon leiomyosarcoma

GI

gastrointestinal

GIST

gastrointestinal stromal tumor

IHC

immunohistochemistry

LMS

leiomyosarcoma

MM

muscularis mucosae

MP

muscularis propria

p

pathological

SM

submucosa

INTRODUCTION

LMSs usually originate from smooth muscle, which is widespread in the body. LMSs are most common in the retroperitoneum (including the pelvis), large blood vessels (principally the inferior vena cava), and the lower extremities.¹⁾ GI LMSs are uncommon neoplasms that arise from the MM or MP, and CLMS is an extremely rare neoplasm, accounting for less than 0.1% of all colorectal malignancies.²⁾

Immunohistochemically, true GI LMS expresses smooth muscle actin (SMA) and desmin without the expression of GIST markers (CD117, CD34, and DOG1) and KIT mutations, which allow LMS to be distinguished from other mesenchymal neoplasms.³⁾

Before the introduction of the oncogenic role of KIT by IHC in 1998, most of the GI LMSs were wrongfully diagnosed as leiomyoma or leiomyoblastomas, particularly GISTs.⁴⁾

GISTs are the most common mesenchymal GI malignancies, with an incidence of 1%–3% of all GI malignancies. Moreover, GI LMS is an extremely rare cancer representing 3%–6% of all GI mesenchymal tumors.⁵⁾ In the past, before the diagnosis of KIT mutations by IHC, the prognosis of CLMS was generally considered to be a benign tumor that displayed optimism with a low propensity for recurrence and distant metastasis.⁶⁾ Later on, the number of reports on true CLMS has rapidly decreased, and those reports have shown that frequent recurrences and distant metastasis have been observed in the CLMS.⁷⁾

Due to the paucity of data about CLMS, the information regarding its clinical characteristics, specific treatment, and influencing prognostics factors is still unclear. Herein, we present a case of CLMS that arose from MM, and attempt to show its clinicopathological characteristics, therapeutic maneuvers, and prognostics predictive factors by reviewing previously published manuscripts.

CASE PRESENTATION

A 73-year-old female presented to our institution for a total screening colonoscopy. She was found to have a Bormann’s type 2 tumor located in the transverse colon (Fig. 1A). CT colonography showed a 3-cm intradural mass in the middle transverse colon (Fig. 1B and 1C), and PET-CT revealed a mildly enhanced mass (Fig. 1D). There was no evidence of distant metastasis in these imaging examinations. The IHC findings showed the spindle-shaped tumor cells (Fig. 1E) that were positive for SMA, desmin, and negative for KIT, CD34 (data not shown). According to the IHC findings, the tumor was diagnosed as a CLMS. At that time, she sometimes suffered from abdominal pain. We were concerned that the symptoms indicated the pre-obstruction due to the tumor, and decided to perform laparoscopic surgery with lymph node (LN) dissection. The resected specimen (Fig. 2A and 2B) showed that the tumor contained a proliferation of spindle-shaped cells arranged in a fascicular pattern (Fig. 2C), which was immunohistochemically positive for desmin (Fig. 2E), SMA (Fig. 2F), h-caldesmon, CAM5.2, and EMA (data not shown), and negative for c-kit, AE1/AE3, CD34, and S-100 (data not shown). The Ki67 and MIB1 labeling indices were both at 70% in the hot spot. Moreover, the tumor bottom was not continuous with MP and had a clear border in the SM layer (Fig. 2D–2F). According to these findings, we finally diagnosed it as primary CLMS arising from MM.

Fig. 1 (A) Colonoscopy findings: A Bormann’s type 2 tumor was located in the transverse colon. (B, C) CT and CT colonography findings: CT and colonography revealed a 3-cm intradural mass in the middle transverse colon (circle and purple-colored mass). (D) PET-CT findings: PET-CT showed a mildly enhanced mass in the transverse colon (circle); there was no evidence of distant metastasis. (E) Pathological examination: The pathological finding revealed the spindle-shaped tumor cells (100 μm, scale bar)./ / PET, positron emission tomography/ /

Fig. 2 (A) The resected specimen: The tumor dimension was 3.0 × 2.4 cm. (B, C) H & E staining images: Macroscopic finding (B, 5 mm, scale bar) and microscopic finding (C, 100 μm, scale bar): The tumor contained a proliferation of spindle-shaped cells, arranged in a fascicular pattern. (D) Microscopic H & E findings (500 μm, scale bar, square in B): There was a border between the tumor and the MP in the submucosa layer. (E, F) Microscopic IHC findings (100 μm, scale bar, square in B): The tumor was immunohistochemically positive for desmin (E) and SMA (F), and the desmin staining revealed that tumor bottom was not continuous with MP (E)./ / H & E, hematoxylin and eosin; IHC, immunohistochemistry; MP, muscularis propria/ /

After the surgery, she did not receive adjuvant chemotherapy. We performed close follow-up and regular imaging examinations, and there was no evidence of recurrence 24 months after the resection.

DISCUSSION

CLMSs are extremely rare neoplasms, and the prognosis has generally been considered poorer than that of other colon malignancies.⁷⁾ Most of them have been described as case reports, and their clinical characteristics and specific treatment are still unknown.

We searched the PubMed database using the MeSH terms “leiomyosarcoma” and “colon.” Only English-language reports published after 2000 were included. All cited references were also reviewed. The search yielded 200 publications; there were 51 published cases of CLMS that underwent surgery and were clearly diagnosed by IHC staining. Table 1 summarizes these data, including our case.^{2,4,5,8–39)} The patients consisted of 32 males and 20 females, with a median age of 65 years (range, 24–94 years). There were 26 right-side colon cases and 26 left-side cases, most frequently in the sigmoid colon (19 cases). The median tumor size was 5.7 cm (median, 1–23 cm). There were 31 cases of localized disease and 11 cases with distant lesions (10 cases were not described).

Table 1 Summary of all selected cases and our case

[Table Omitted: See PDF]

A, ascending colon; Adjuvant, adjuvant chemotherapy; C, caecum; D/D, dead of difference disease; D, descending colon; DOX, doxorubicin; DTX, docetaxel; EPI, epirubicin; F/U, follow up; F, female; GEM, gemcitabine; IFM, ifosfamide; LN, lymph node; M, male; MP, muscularis propria; NA, not available; Ref., reference; S, sigmoid colon; SE; Serosa; SM, submucosa; SS, subserosa; T, transverse colon

CLMSs can develop from both the MM and MP membranes, but developed from MM is uncommon.⁵⁾ There were 10 of pathological (p) MP cases that indicated CLMS arising from the MP membrane (Cases 18,¹³⁾ 31,²²⁾ 34,²⁴⁾ 36,²⁵⁾ 38,²⁷⁾ 40,²⁹⁾ 46,³⁴⁾ 48,³⁶⁾ 49,³⁷⁾ 51³⁹⁾; Table 1), and 5 pSM cases (Cases 16,¹³⁾ 35,⁵⁾ 37,²⁶⁾ 45,³³⁾ and ours; Table 1) that arose from MM. Table 2 summarizes the clinicopathological characteristics of pSM and pMP CLMS cases. The results showed that all pSM cases had not developed recurrent tumors and were alive, with a longer follow-up period. Wang et al. reported that smaller tumor size (<8 cm) and younger age (<60 years) were favorable factors for better survival in CLMS patients.⁴⁰⁾ According to the summary (Table 2), the developing membrane of CLMS is assumed to be associated with its malignant aggressiveness and the survival of CLMS patients. Therefore, the histological diagnosis of which membrane CLMS has arisen from is very important and beneficial for predicting the clinical outcomes of the disease. This prognostic factor has never been reported in previous manuscripts.

Table 2 Summary of pSM and pMP mural involvement cases of CLMSs’ clinicopathological characteristics

[Table Omitted: See PDF]

CLMS, colon leiomyosarcoma; F/U, follow up; MP, muscularis propria; N, number; p, pathological; SM, submucosa

Surgery is considered the standard treatment for CLMS, but the significant of LN dissection is still unknown because lymph node metastasis of CLMSs is rather uncommon.²⁷⁾ However, there were 3 cases of localized disease with LN metastasis (Cases 16,¹³⁾ 38,²⁷⁾ 51³⁹⁾; Table 1) and 1 case of heterochronic LN recurrence (Case 39²⁸⁾; Table 1). CLMSs frequently behave aggressively,⁷⁾ so it seems to be better to perform LN dissection for curative surgery, similar to the approach for colorectal adenocarcinoma.

Smrke et al. showed that recurrence is a significant risk factor for poor prognosis even with complete oncological resection.⁴¹⁾ In the reviewed 52 cases (Table 1), the liver was the most common site of metastasis site (8 cases), and the recurrence sites were of equivalent frequency in the liver and lung (6 and 4 cases, respectively). Most of them received doxorubicin and/or ifosfamide treatment according to standard therapy for LMSs. However, the effectiveness of chemotherapy is unclear for distant metastasis and recurrence cases of CLMS. Some literature reported cases that underwent radical resection for distant lesions and/or recurrence sites.^19,37,38) Those reports suggested that long-term survival was achieved after wide surgical excision with negative margins. Radical resection possibly contributes to prolonged survival in patients with metastasis and recurrence diseases.

Several cases received adjuvant chemotherapy after curative surgery (Case 13,¹¹⁾ 19,¹⁴⁾ 25,¹⁹⁾ 28,¹⁹⁾ 43³¹⁾, 48³⁶⁾; Table 1); however, the benefits of adjuvant chemotherapy for CMLS are still controversial because of inadequate follow-up time and limited case numbers.

In the present case, she was older than 60 years, but the tumor size was smaller than 8 cm and it was a pSM tumor. Considering there was no evidence supporting adjuvant chemotherapy, we decided to select careful and short-term observation without adjuvant chemotherapy. She has been alive 24 months after the surgery.

CONCLUSIONS

This literature demonstrates CLMS arising from MM and suggests that pathological diagnosis is associated with prognosis, as shown by a review of previously reported cases.

DECLARATIONS

Funding

This manuscript was not funded externally.

Authors’ contributions

Y Kasagi and MS wrote the manuscript.

MS, TN, and AI performed the surgery.

Y Kasagi and MM participated in the surgery.

Y Kasagi, MS, TN, RY, MT, NK, AI, Y Kimura, and MM participated in the study design and coordination.

Y Koga and KT developed the histological staining and diagnosed the findings.

MS and Y Kasagi performed the overall organization of writing the manuscript.

All authors read and approved the final manuscript.

Availability of data and materials

Data sharing is not applicable to this article, as no datasets were generated or analyzed during the current study.

Ethics approval and consent to participate

This work does not require ethical considerations or approval, and informed consent to participate in this study was obtained from the patient.

Consent for publication

Consent was obtained from the patient and the patient’s family for the publication of this case report and accompanying images.

Competing interests

The authors declare that they have no competing interests.

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