GISTs are the most common mesenchymal GI malignancies with the incidence of 1–3 % of all GI malignancies. Moreover, LMS is an extremely rare cancer representing 3–6% of all GI mesenchymal tumors. They arise from muscularis mucosae or propria occurring mostly in middle-aged males[3, 4]. In the pre-KIT area, most of the GI mesenchymal malignancies were wrongfully diagnosed as leiomyoma, LMS, or leiomyoblastomas. However, their incidence declined after the diagnosis of KIT mutations and the immunohistochemical differences between LMS and other GI mesenchymal tumors, particularly GISTs[5].
In 1998, Hirota et al identified the presence of activating KIT-mutations in 94% of GISTs[6]. Kit gene, a tyrosine kinase receptor proto-oncogene, causes increased cellular proliferation. Subsequently, this mutation can lead to cellular atypia and neoplasia. Later studies confirmed that 95% of GISTs expressed CD34, CD137, and DOG1.1 [7]. On the contrary, the LMS is negative for kit-mutations and mostly positive for desmin, SMA, h-caldesmon, and vimentin[8].
Differentiation between LMS and GISTs is paramount importance since they have very similar clinical presentations but require radically different courses of treatment. The cellular origin of GISTs, the interstitial cells of Cajal, was first introduced in mid-1990s. however, LMS originates from muscle fibers of the muscularis mucosae and muscularis propria [9]. Most of the colon LMS are polypoid, while esophageal LMS is mainly intramural[10].
The most common location of GI involvement in GISTS is in the stomach (55%), small intestine (29%), colon (2.9%), and rectum (2.7%) [11]. Furthermore, GI LMS mainly involves stomach followed by small intestines, rarely colon and rectum[12]. True LMS of the colon is such a rare disorder that there isn’t enough description of its nature. The classical colon LMS presents with a vast majority of non-specific symptoms including mild abdominal pain, fresh/obscure rectal bleeding, intra-abdominal hemorrhage, weight loss, changes in bowel habits, bowel obstruction, and tenesmus. [13] Diagnosis is based on colonoscopy and histologic evaluation and IHC profiling.
Based on our survey, there are only thirty-four previous cases of published colonic LMS after the pre-kit era that was confirmed with immunohistochemistry (Table 1). The most common location for colonic LMS is the sigmoid colon, followed by the ascending colon. The prognostic factors for the disease outcome have not been established properly. The most important prognostic factor for survival and recurrence seemed to be age, tumor grade, disseminated disease and tumor size[14]. Yamamoto et al, concluded that the only negative predictive factor for survival is tumor size of more than 5 centimeters[15]. However, based on previous case studies local and distal recurrence occurred even with favorable tumor features[13]. Compared with adults, infantile LMS has a better prognosis even with poor histologic features[16].
Table 1
All cases of published colonic LMS after the pre-kit era.
Case | Year | Age | Sex | site | Size (CM) | Local recurrence | Metastasis | survival | c-kit | α-SMA | Desmin | CD-34 |
---|
1[23] | 2000 | 54 | M | D | 3.2 | U | U | Dead | Neg | Pos+ | Pos+ | Neg |
2[23] | 2000 | 61 | M | A | 4.2 | None | None | Alive | Neg | Pos+ | U | Neg |
3[23] | 2000 | 75 | M | A | 6.5 | U | U | Dead | Neg | Pos+ | U | Neg |
4[23] | 2000 | 76 | F | C | 7.8 | U | U | Dead | Neg | Pos+ | U | Neg |
5[23] | 2000 | 36 | F | S | 6.5 | None | Lung | Dead | Neg | Pos+ | Pos+ | Neg |
6[23] | 2000 | 66 | M | A | U | None | Liver | Dead | Neg | Pos+ | U | Neg |
7[23] | 2000 | 41 | M | C | 7.5 | None | Humerus | Alive | Neg | Pos+ | Pos+ | Neg |
8[24] | 2004 | 65 | M | D | 10 | None | Positive(U) | Dead | Neg | Pos+ | Pos+ | Neg |
9[25] | 2004 | 67 | F | T | 5.7 | None | None | Alive | Neg | Pos+ | U | Neg |
10[10] | 2007 | 77 | F | S | U | Positive | None | U | Neg | Pos+ | Pos+ | Neg |
11[10] | 2007 | 52 | M | S | U | None | Liver | U | Neg | Pos+ | Pos+ | Neg |
12[26] | 2009 | 74 | F | A | 6 | None | Lung | Dead | Neg | Pos+ | U | U |
13[27] | 2011 | 70 | F | S | 3.7 | None | None | Dead | Neg | Pos+ | Pos+ | Neg |
14[27] | 2011 | 56 | M | C | U | None | Liver | Alive | Neg | Pos+ | Pos+ | Neg |
15[28] | 2012 | 66 | F | S | 3 | None | Liver | Dead | Neg | Pos+ | Pos+ | Neg |
16[15] | 2013 | 94 | F | D | 25 | None | Liver | Dead | Neg | Pos+ | U | Neg |
17[15] | 2013 | 56 | M | S | 1 | None | LN | Alive | Neg | Pos+ | U | Neg |
18[15] | 2013 | 78 | F | S | 8.5 | None | Lung | Dead | Neg | Pos+ | U | Neg |
19[15] | 2013 | 87 | M | T | 11 | None | None | Dead | Neg | Pos+ | U | Neg |
20[29] | 2013 | 65 | M | S | U | None | None | Alive | Neg | Pos+ | U | U |
21[30] | 2014 | 66 | F | T | 4 | None | None | Alive | Neg | Pos+ | U | Neg |
22[29] | 2014 | 65 | M | S | U | None | None | Alive | Neg | Pos+ | U | U |
23[5] | 2015 | 46 | M | T | 11.8 | Positive | None | Alive | Neg | Pos+ | U | Neg |
24[31] | 2015 | 89 | F | A | 4.5 | None | Liver | U | Neg | Pos+ | U | U |
25[4] | 2015 | 54 | M | A | 13 | Positive | None | Alive | Neg | Pos+ | Pos+ | Neg |
26[32] | 2015 | 59 | M | A | 10 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
27[33] | 2016 | 89 | M | C | 2.2 | None | None | Alive | Neg | Pos+ | Pos+ | U |
28[34] | 2016 | 51 | F | D | 4 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
29[35] | 2016 | 44 | M | SF | 8.5 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
30[8] | 2017 | 55 | F | A | 8 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
31[13] | 2018 | 57 | F | S | U | U | U | Alive | Neg | Pos+ | U | Neg |
32[13] | 2018 | 88 | M | A | 6.5 | None | Liver | Dead | Neg | Pos+ | U | U |
33[36] | 2019 | 53 | M | S | 3.5 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
34[3] | 2019 | 46 | M | S | 4.2 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
35(case1) | 2019 | 48 | M | S | 7.2 | None | None | Alive | Neg | Pos+ | Pos+ | Neg |
36(case2) | 2020 | 49 | M | S | 4 | None | Peritoneum Lungs | Alive | Neg | Pos+ | Pos+ | Neg |
According to the recent survey by Faraj et al., lymph node involvement is very unlikely and distant metastasis is mostly by hematogenous spread[17]. Liver is the most common site of secondary tumor metastasis followed by lungs and peritoneum.[17] Due to the paucity of data, there is not enough evidence to establish reliable mortality estimates. However, based on a study by Aggarwal et al. in 2012 only 2 of 11 cases of colon LMS survived in 5-year surveillance[1]. The main cause of death was spreading of the primary tumor and multiple organ failure[1].
Medical therapy is the main course of treatment in mesenchymal GI malignancies, particularly GISTs. However, Due to absence of KIT-mutations in LMS, tyrosine kinase inhibitors (TKI) are not effective in tumor treatment. Therefore, Surgery is considered as the gold standard treatment for LMS[18]. Since, there are only a few numbers of true LMS cases reported, no standard therapeutic strategy has been established. Radical excision is the most reasonable option since even with low-grade tumors recurrences occurred[19]. According to YTNM Lee et al., all cases of smooth muscle sarcomas, should undergo wide excisional surgery with 4 cm tumor margin involving mesentery[20].
Although lymph node involvement is very uncommon in LMS, lymph node dissection is recommended due to its highly invasive nature[3, 15]. Anthracyclines, first-line conventional chemotherapy regimen for soft tissue sarcomas, have minimal to no effect on LMS. A multi-drug regimen of Doxorubicin plus dacarbazine may have some clinical response in treatment. In conclusion, Adjuvant chemotherapy is unnecessary when tumors are completely resected. [18]. However, neoadjuvant chemotherapy may decrease the risk of local recurrence in some cases of rectal sarcomas[21]. Furthermore, radiotherapy is completely unbeneficial since LMS is highly radio-resistant[22].