DISCUSSION
Cystica profunda is a rare benign non-neoplastic disease that can occur throughout the gastrointestinal tract, mostly in the rectum, followed by the colon, and more rarely in the stomach and small intestine. It is also known as gastritis cystica profunda (GCP), enteritis cystica profunda (ECP), and colitis cystica profunda (CCP)[4]. CCP is a rare benign disease occurring in the rectum or colon, most commonly in the anterior wall of the rectum. The pathogenesis of CCP is unknown and is thought to be due to congenital or acquired mucosal muscle weakness caused by inflammation, infection, trauma or ischemia resulting in embedding of the mucosal epithelium in the submucosa [5]. The main histological features are the presence of multiple cysts of varying size and morphology in the submucosa lined with a single layer of flattened or columnar epithelial cells, which are filled with mucus, and the disappearance of some of the covered epithelium of the cyst wall, forming a mucus lake[6].
CCP can occur at any age, most common in young and middle-aged people aged 30-40 years, and is more common in men. The clinical manifestations of CCP are diverse and nonspecific, mainly including abdominal pain, diarrhea, constipation, blood in stool, mucus stool, urgency, rectal pain, change in stool habit, internal rotation, abdominal mass and intestinal obstruction [7-9]. According to the extent of invasion, there are diffuse and local types[10]. The diffuse type involves the entire colon with villous or tipped polypoid lesions or even ulcers, mostly due to intestinal inflammation and ulceration. It is associated with Crohn’s disease, ulcerative colitis, infectious colitis and radiation enteritis[11,12]. The local type is mostly seen in the anterior wall of the rectal 5-12 cm from the anal verge, presenting as nodules or polyps, which is associated with rectal prolapse and isolated rectal ulcer syndrome. The local type is the most common, while the diffuse type accounts for less than 15% of cases reported in the literature [1,3,13,14]. Both of the two cases in this paper were young and middle-aged patients with clinical characteristics of mucous excretion. The locations of all cases were located in the anterior rectal wall of 5-12cm from the anal verge, which was consistent with the location reported in the literature. Both cases showed nodularity and belonged to the local type.
The imaging findings of CCP are characteristic. X-rays are normal or nonspecific in the early stage, or show luminal narrowing and irregularity due to multiple submucosal cystic structures. Barium enema shows single or multiple filling defects or shows thickened folds. CT images show a non-infiltrating submucosal mass with well-defined borders and an unenhanced cystic lumen of variable sizes. The perirectal adipose tissue was absent and the levator anus muscle was thickened[2,15]. MRI showed a homogeneous low signal on T1WI and a submucosal high signal nodule on T2WI, with no significant enhancement on contrast-enhanced images, high signal on DWI, no diffusion restriction on ADC, and significant high signal on T2WI suggesting that the presence of mucin in the lesion[4,16]. In both cases in this paper, CT showed non-enhancing hypodense lesions with clear borders, calcifications at the margins, smooth mucosa, intact rectal wall, clear surrounding fatty spaces, and no enlarged lymph nodes. MRI presentations were also consistent with the above imaging manifestations. However, the thickening of the levator anus muscle described in the literature was not present. In addition, the presence of calcification of the cyst wall was described in our case, which suggests a chronic benign disease and not associated with rectal cancer where calcification usually inside the tumor [17].
Colonoscopy in CCP shows tipped or villous polypoid lesions covered by normal, edematous or ulcerated mucosa, or shows polypoid or nodular mucosal thickening with or without ulceration, which can be easily confused with colorectal cancer [8]. In contrast, colonoscopy allows biopsy and therefore has the dual advantage of obtaining both imaging and pathology at the same time. However, due to insufficient depth of biopsy and limited sampling, it is easy to missed diagnosis and misdiagnosis. In case 2, the results of the first external colonoscopy biopsy only showed chronic inflammation of the mucosa with erosion, which may be related to the shallow and limited sampling.
ERUS showed multiple hypoechoic or anechoic cysts in the submucosal layer of the rectum with a small amount of internal echogenicity, no involvement of the mucosal layer, no lymphadenopathy, and no penetration or invasion of the muscular layer beyond the submucosal layer[4,9]. In this paper, ERUS showed cystic lesions in the submucosal layer in both cases, with the mucosal and serous layers intact. The difference between the two cases is that the lesion was located in the submucosal layer and the intrinsic muscular layer, with invasion of the muscular layer in case 1. While in case 2, the lesion was located only in the submucosa, and the intrinsic muscle layer was not invaded outside the submucosa. ERUS can clearly localize the different layers of the intestinal wall and can assess whether the mucosal layer, intrinsic muscular layer, and serous layer of the intestinal wall are intact. Although ERUS cannot confirm the diagnosis, it is of great importance to exclude malignant tumors in the deeper layers of the intestinal wall. Moreover, ERUS is safe, noninvasive, nonradioactive, easy to perform, well tolerated, and can be repeated as a follow-up examination.
CCP is similar to benign and malignant colorectal tumors and inflammatory bowel disease, and the diagnosis of CCP also requires the identification of any colon or rectal polypoid or intramural benign or malignant masses (adenomatous polyps, polypoid inflammatory granulomas, leiomyomas, lipomas, adenocarcinomas, mucinous carcinomas, sarcomas), inflammatory lesions (ulcerative colitis, Crohn’s disease, and ischemic colitis or proctitis), and endometriosis [10].
The goal of treatment for CCP is to prevent or reduce symptoms. Depending on the severity of symptoms, treatment can be either conservative medical or surgical. Patient education and behavior modification are the primary treatments for patients with CCP. Conservative treatment includes bowel habits, postural correction, avoidance of stress and strain, and increased dietary fiber can alleviate symptoms in the majority of patients. Conservative treatment is ineffective and surgical resection is required when symptoms are persistent or severe, such as bowel obstruction, bleeding, or rectal prolapse[18,19]. In recent years, endoscopic submucosal dissection (ESD), with the advantages of rapid recovery, minimal trauma, and preservation of colonic integrity, has been widely used in the treatment of CCP [20].
In conclusion, CCP is a rare disease that is difficult to diagnose and easily misdiagnosed as other occupying lesions of the intestine because of its low incidence, lack of specificity in clinical and endoscopic manifestations, and lack of awareness among physicians in various disciplines. Once misdiagnosed, it not only brings unnecessary painful surgical resection to patients, but also poses risks to physicians. In contrast, imaging study plays a crucial role in both disease detection and differentiation from malignant diseases, helping to initially determine the benignity and malignancy of the lesion and avoiding erroneous radical resection surgery.
ACKNOWLEDGMENT
Supported by the program of Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004).