A laterally spreading tumor (LST) of the rectum with lymphatic metastasis: a case report and literature review

doi:10.21203/rs.3.rs-2754271/v1

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Case Report

A laterally spreading tumor (LST) of the rectum with lymphatic metastasis: a case report and literature review

https://doi.org/10.21203/rs.3.rs-2754271/v1

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Background: Colorectal cancer (CRC), as one of the most common gastrointestinal malignancies (10.0% of total cancer cases), is also the second leading cause of cancer death (9.4% of the total cancer deaths). Morphologically, early colorectal tumors could be divided into 3 groups: protruded tumors, depress tumors and laterally spreading tumors. Laterally spreading tumors (LSTs) are defined as lesions >10mm in diameter and extending laterally along the luminal wall, by first proposed by Kudo, a Japanese scholar, in 1993. In recent years, the incidence of LSTs has significantly increased. However, LSTs in the rectum with lymphatic metastasis are rarely report.

Case presentation: Our team reported a 69-year-old man with abdominal pain, diarrhea and a rectal LST 7 cm in diameter. The rectal lesion was initially diagnosed as a tubulovillous adenoma and some areas show high-grade intraepithelial neoplasia. A therapeutic strategy of laparoscopic assisted radical resection of low rectal cancer (Dixon, D3, TME) was applied. The surgeries and postoperative procedure went smoothly.

Conclusions: This is a rare and clinically significant case that demonstrates the possibility of lymph node metastasis in early intramucosal carcinoma and focuses on the diagnostic and therapeutic schedule of early colorectal cancerous lesions.

Laterally spreading tumor

Intramucosal carcinoma

Lymphatic metastasis

Early rectal cancer

With the increasing incidence of laterally spreading tumors (LSTs), it has become one of the most important precursor lesions of colorectal carcinoma[1]. Morphologically, LSTs can be divided into two categories: granular type (LST-G) which is consisted of superficially spreading aggregates of nodules, forming flat, extensive and granular lesions with uneven surfaces, and non-granular type (LST-NG) which is defined as a lesion with a flat, smooth surface and lacking of granulonodular formation[2, 3]. One study showed that among all the colorectal LST, LST-G was much more common than LST-NG[4]. It is widely known that these two types of tumors differ not only in morphology but also in clinicopathological features[5]. LSTs are generally deemed to be less invasive because neoplastic cells tend to spread along the luminal surface, and these tumors are most likely to be found in the early stage of cancer: the adenoma stage. But it has been reported that the submucosal invasion rate and carcinoma incidence rate are higher in LST-NG than LST-G[6]. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are considered the standard management methods for the resection of LSTs as they extend laterally rather than perpendicularly[7]. However, for intramucosal carcinoma with lymph node metastasis, submucosal infiltrating carcinoma, negative lift sign after submucosal injection, and unsuitable lesion sizes or locations for endoscopic treatment, surgical treatment was directly adopted. In this case, the LST was large and involved the middle and upper segment of rectum with a wide range. After debating at a multi-disciplinary meeting, as the lesion was suspected to be an early rectal cancer and its large tumor size, our team suggested this patient to undergo a surgical resection.

A 69-year-old man with abdominal pain and diarrhea visited the Affiliated Hospital of Qingdao University for evaluation. On admission, the patient had hematochezia and anaemia without other symptoms such as abdominal pain, abdominal distention, nausea and vomiting and weight loss. His medical history mainly included hypertension (40-years), which was well controlled by regular medicaton. And he denied malignant tumor, heat disease, diabetes, and hereditary disease and contagious disease. Initial laboratory investigations were insignificant except a high total cholesterol level of 7.09 mmol/L and a low density lipoprotein level of 4.44 mmol/L. Abdominal CT revealed a space occupying lesion of rectosigmoid and progressive cysts in both kidneys. High resolution dynamic enhanced MRI of rectum showed that the distance of the lesion’s lower margin from the anal margin was about 104 mm and superior and inferior margin of the lesion were about 56 mm, and the lesion was significantly enhanced (Fig. 1A, B, C). The depth of lesion invasion was about 4 mm (Fig. 1D, E). Neither distant tissue or organ metastasis nor lymph-node invasion was observed.

The endoscopy showed there were about 15 sessile flat and short-pedicled polyps with a size of 5 to 15 mm in the whole colon (Fig. 2a, b, c), and a large multilobed sessile polypoid mass in the rectum, which from the dentate line about 7 cm (Fig. 2d, e, f). At its maximum, the lesion was 7 cm long and involved about three fourths of the rectal circumference. Based on its appearance and surface features, the LST was categorized as a non-ulcerative G type (granular/granulonodular) lesion. No obvious pigment deposition area was found after spraying Methylene Blue. Biopsy specimens disclosed tubulovillous adenoma.

Later the patient underwent laparoscopic-assisted radical resection (Dixon, D3, TME) for lower rectal cancer and subsequent abdominal drainage. Intraoperative exploration revealed that the tumor was located 3 cm above peritoneal reflection, on the left side of the anterior wall of rectum, with a diameter of about 5 cm. The intestinal segment of tumor, mesangial and retroperitoneal lymph node adipose tissue were completed resected (Fig. 3a). However, postoperative pathologic examination of the resected tissue revealed extensive tubulovillous adenoma, parts of the tumor show extensive high-grade intraepithelial neoplasia and intramucosal adenocarcinoma (Fig. 3b, c, d, e). According to haematoxylin and eosin stain, the tumor depth was limited to the mucosal layer, but there were two well-differentiated glandular configuration in the regional lymph nodes (Fig. 3f). Since ectopic colorectal mucosal lymph nodes were rarely reported, it was still considered as lymph node metastasis.

As a result, the patient recovered smoothly without complication of operation and discharged at 10 days postoperatively in a stable condition.

This report gives a description of a rare case of large laterally-spreading tumor with lymph node metastasis in the rectum. LSTs are generally defined as non-polypoid neoplasms > 10 mm in maximum diameter that extend laterally along the intra-luminal wall of the intestine, represent the majority of nonpolypoid colorectal neoplasms[2, 8]. This is in contrast to traditional polypoid (grow upwards) or flat and depressed lesions (grow downwards). And it is generally considered to be less invasive into the submucosa and deeper layers. According to endoscopic morphology, LSTs can be divided into granular type (LST-G) and non-granular type (LST-NG). The former is subdivided into homogeneous type (LST-GH) and nodular mixed type (LST-GM), while the latter is further divided into flat elevated type (NG-F) and pseudo-depressed type (NG-PD)[2]. But LST-GM has many forms, sometimes it is difficult to distinguish the LST-GH and the LST-GM. This case belongs to LST-GM according to the above classification criteria. LSTs are easily missed during a white light endoscopy owing to the subtlety of the morphologically changes[3, 9]. The detection rate and diagnostic accurary of LSTs can be improved by advanced imaging techniques such as narrow band imaging (NBI) and magnifying chromoendoscopy (MCE), and by using these diagnostic techniques, the depth of invasion of colorectal neoplasms could be precisely evaluated before selecting an appropriate therapeutic schedule[10, 11]. However, it’s not possible to assess a giant polyp by endoscopy across the board, including unobvious changes around the lesion that might indicate tumor invasion or lymphatic metastasis.

As one of the precancerous lesions of colorectal cancer, LSTs are closely related to colorectal cancer. The histological types of LSTs are mainly adenomatous, including tubular, including tubular, villous, tubular-villous and serrated adenoma. Others include inflammatory, hyperplastic, juvenile polyps and so on. It has been reported that villous adenomas have the highest rate of carcinogenesis[12]. Studies have found 45%~79% of LST lesions have high-grade intraepithelial neoplasia or submucosal invasiveness[13]. Other researchers have suggested that some LSTs with high-grade intraepithelial neoplasia can rapidly infiltrate into the submucosa in the central depression, and the gross morphology is usually Ⅱa or Ⅱa+Ⅱc. These LSTs are thought to develop through the de novo pathway[14]. That is, without adenoma development stage, directly becoming cancer from normal intestinal mucosa, the normal intestinal, and its onset is insidious, but its malignant degree is high[15]. LSTs have a higher malignancy potential than traditional protruded-type adenomas. Some studies have shown that the predilecting sites, diameter size and morphologic categorization are all risk factors related to malignant of change of cancerization[16]. According to Sanduleanu that 19% of the LST-G and 39% of the LST-NG were dected to contain submucosal invasion, with deep infiltration accounting for 79% and 54%, respectively[17]. LST-NG type has a higher malignant potential than LST-G type[18]. LSTs may have different molecular mechanism of malignant transformation from other adenomatous polyps. The development of LSTs into cancer is a process of accumulation of a series of genes level and epigenetic changes, involving the activation of protooncogenes, inactivation of tumor suppressor genes, mismatch repair genes and apoptosis related genes mutations, etc. The main molecular mechanisms include KRAS mutation, APC mutation, p53 overexpression, GANS mutation, CpG islands methylation, etc. In addition, some molecules are also believed to be related to the occurrence and malignant transformation of LSTs. For example, Ki67, mucin 1 (MUC1), Cyclin D1, BRAF, MLH1 also have certain differences in the expression of colorectal cancer, LSTs and protruded adenoma[19, 20]. In terms of treatment, compared with traditional protruded-type adenomas, active intervention should be performed while LSTs are found under colonoscopy. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are considered the standard management approach for the removal of LSTs[7, 8]. Previous studies have shown that EMR should be the first-line treatment when an LST demonstrated: 1) flat nodules without depression, or 2) uneven nodules without depression and less than 3mm in diameter, because the risk of substantial submucosal invasion of above LSTs is low. Prak et al. retrospectively analyzed that endoscopically resected LSTs with positive lateral margin have a low recurrence rate (6.3%)[21]. European Society of Gastrointestinal Endoscopy (ESGE) recommends en bloc EMR is generally limited to lesions 20mm in size, and characteristics associated with incomplete resection or recurrence include lesion size > 40 mm, the location of ileocecal valve, priorfailed attempts at resection[22]. For large (> 20 mm) laterally spreading lesions, endoscopic piecemeal muscosal resection (EPMR) could be selected for resection. However, it’s impossible to evaluate submucosal invasion and vertical depth accurately because piecemeal resection has been performed. Compared with en bloc resection, piecemeal resection is associated with a higher rate of incomplete resection (20%) and local recurrence (3%)[23]. Therefore, ESD has become a minially invasive endoscopic technique for the en bloc resection of large LSTs[7]. ESD provides higher intact resection rates, larger specimens, and allows for more accurate histopathological analysis than EPMR. But ESD for colorectal tumors is not widespread because of its complicated procedures, longer operation times, and high risk of perforation and bleeding compared with EMR[24].

Theoretically, if the tumor is completely contained within the mucosa, the risk of lymph-node and vascular invasion is almost zero, therefore, endoscopic resection is a legitimate treatment for these lesions. If the risk of submucosal invasive carcinoma within the LST is considered high, and en bloc EMR cannot be achieved, ESD or surgery is recommended[22]. If there is submucosal invasion, extension into endothelilum-lined vascular spaces is considered an important risk for lymph-node invasion or distant metastases. The increased risk is proportional to the depth and width of submucosal infiltration. When invasion is extensive, surgery is required. If the lesion is in the rectum, surgical options may include abdominperineal resection, transanal resection, low anterior resection, and transanal endoscopic microsurgery, depending on location, size, and other features of the lesion. Up to now, surgery is the gold standard of treatment, and no study certifies that ESD has better outcomes than surgery. In most cases, surgery has the added benefit of removing the local lymph nodes. The rectum may be a exception, due to the complexity of traditional surgical procedures, there is a higher risk of poor functional outcomes which prompt ESD take the place of surgery. Therefore, the boundary between endoscopic or surgical treatment should be estimated before treatment.

This case is a new discovery, and has directed significance of treatment and diagnosis for the gastroenterologist. For the laterally spreading tumor or early colorectal cancer, regional lymphatic metastasis is possible even if the lesion confined to the mucosa. However, we still don’t know exactly how this lymphatic micrometastasis happens. The early diagnosis and curative treatment of LST lesions are crucial for better patient outcomes. In particular, larger lesions or those with granules and nodules should be surgically resected rather than by endoscopic resection due to their high risk of invasiveness and malignancy. Our team hope to improve the understanding of these lesions from this case and promote the diagnosis and treatment strategies of LSTs and early colorectal cancer.

Data Availability Statement

The original data supporting the conclusions of this paper will be provided by the authors, without unnecessary reservation to any qualified researcher.

Ethics Statement

Any potentially identifiable data or images published in the article have been given written informed consent by the patient.

Authors’ Contributions

All authors have made significant contributions, and all agree with the contents of the manuscript.

Funding

None.

Conflict of Interest

The authors state that the study is conducted without any commercial or financial relationships that could be interpreted as a conflict of interest.

ORCID

Ben Li: https://orcid.org/0000-0002-3417-0521

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No competing interests reported.

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A laterally spreading tumor (LST) of the rectum with lymphatic metastasis: a case report and literature review

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