Mesenteric panniculitis (MP) is an idiopathic, localized inflammation involving the adipose tissue of the small bowel mesentery. The association of mesenteric panniculitis with malignancy, predominantly lymphomas, has been widely reported in the medical literature. The majority of patients with mesenteric panniculitis are asymptomatic and are picked up incidentally while performing radiological examinations, but MP patients with a high risk of malignancy warrant a thorough investigation [1]. There is a lack of clear clinical guidelines on the management and follow-up of MP.

Cardinal radiological signs of mesenteric panniculitis

Table 1 shows the five cardinal radiological signs of MP [1].

Pathology

MP is an inflammatory disorder of the mesenteric root with two distinct pathological subgroups: mesenteric panniculitis and retractile mesenteritis. The differential diagnosis of these two conditions is based on histological criteria; fat necrosis predominates in MP whereas fibrosis and retraction predominate in retractile mesenteritis [2].

The exact diagnosis is often difficult. It is usually made by finding one of three major pathological features: fibrosis, chronic inflammation, or fatty infiltration of the mesentery.

Clinical features

The majority of patients with mesenteric panniculitis are asymptomatic, although some may present with non-specific symptoms like abdominal pain, nausea, vomiting, fever, ascites, and pleural effusion [2].

The condition occurs mostly in middle or late adulthood with a slight male predominance. Symptoms may be progressive, intermittent, or absent. Laboratory findings, including elevation in erythrocyte sedimentation rate and anaemia, are generally absent or non-specific.

Aetiology

Common causes of MP include abdominal trauma and a history of abdominal surgery. Associated inflammatory disorders, such as vasculitis or chronic rheumatic conditions, granulomatous disease, rheumatic disease, malignancies, and pancreatitis have also been reported.

Infectious associations with MP include mycobacterial and cryptococcal infections and cholera. In some patients, especially those having an acute presentation of the disease, viral mesenteritis is likely. Fever of unknown origin and chylous ascites have also been described in patients with MP [3].

Although often entirely isolated, synchronous association of MP has been observed with some neoplastic diseases, such as lymphoma, colorectal cancer, and melanomas. The possibility of MP being a paraneoplastic syndrome in the elderly should be considered [2].

When MP occurs in association with malignancy, the most common primary sites are the large bowel, the lymph nodes, and the urogenital tract. In those with MP, any cancer - with the exception of prostate cancer - can usually be seen on an index computed tomography (CT) scan. Further extensive investigation in asymptomatic patients is therefore likely to be of low yield [4].

Objectives of this literature review

To discuss the clinical features and association between mesenteric panniculitis and malignancy, the diagnostic dilemmas, and their treatment plan.

Materials and methods

We conducted a literature search of articles using the US National Library of Medicine PubMed database, PubMed, MEDLINE, Embase, Cochrane Library and Google Scholar databases, ClinicalTrials.gov for studies, and the ISI Web of Science. No date restrictions were placed on the search. A thorough search for controlled clinical trials and cohort studies was conducted. Since the rarity of condition, case reports were also included.

We used the keywords: "Mesenteric panniculitis" and "malignancy".

Included studies were those published in English that assessed the association between mesenteric panniculitis and malignancy. Reference lists were also screened. From the search results, articles with irrelevant titles were discarded, with the remaining abstracts examined for relevance.

The authors of this review independently determined the eligibility of the studies and assessed the methodology of included studies. In this review article, we will discuss the aetiology, pathogenesis, and clinical studies related to MP, as well as case studies and their management per the latest clinical guidelines.

Review of clinical studies

The findings of the literature review are summarised in Table 2, but we will discuss a few of the studies that are more relevant to the association between mesenteric panniculitis and malignancy.

The authors of this review gathered all the data showing the relationship between mesenteric panniculitis and malignancy. Various variables like study design, age, gender, total number of patients with malignancy, colorectal cancer, pancreatic cancer, lymphoma, cholangiocarcinoma, prostate cancer, breast cancer, bladder cancer, lung cancer, metastases during follow-up, previous abdominal surgery, inflammatory bowel disease, autoimmune disease, and death are gathered and discussed in Table 3. In particular, mesenteric panniculitis and colon cancer are also discussed.

Although prior studies have described the association of MP and malignancy, a recent study shows that only 1.4% of patients with a computed tomography (CT) scan finding of MP will be found to have a previously undiagnosed or suspected cancer [3]. The higher rate of association of MP and cancer described in prior studies likely indicates the inclusion of patients with a known history of cancer.

Additionally, this study shows that a follow-up abdominal CT in patients with cancer suggests stability and not a worsening of MP. Finally, findings indicated that positron emission tomography scans are not recommended in the evaluation of cancer patients with mesenteric panniculitis-like findings on a CT [3].

One retrospective study of 4,758 patients with 90 identified cases of mesenteric panniculitis found that the likelihood of associated malignancy (mostly intra-abdominal malignancy) was 2.1 times higher in patients with MP than those without it [13].

The crude ratio of mesenteric panniculitis patients with colon cancer is less than 10% from our studies (refer Table 4), which is worth looking into. Bigger studies with good sample size and proper research are necessary to further assess it. Even though this is simply a crude ratio, it holds promise for better understanding of the co-occurrence of MP and colon cancer.

Follow-up

Computed tomography scan is optimal for accurate, non-invasive diagnosis of MP and follow-up of sclerosing mesenteritis and any complications. The presence of some radiological findings, such as lymph node size of more than 12 mm and the absence of the fat ring sign, should raise the concern of subsequent malignancy in patients with MP [23].

Treatment

There are no well-established treatment plans for this rare condition. Thus, any treatment prescribed is mainly for symptom relief and to address any complications. Commonly used agents include steroids and other immunosuppressants [24].

One study found that symptomatic patients with idiopathic mesenteric panniculitis responded to treatment with antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) [9]. Patients with obstructive or compressive symptoms may require surgery.

Strengths of the studies

This is one of the most comprehensive literature reviews discussing the association between mesenteric panniculitis and malignancy. The studies in this literature review have been done in multiple centres which will increase the generalisability of the results within a population. Studies also represent a wide range of malignancies like colorectal cancer, lymphoma, breast cancer, etc.

Limitation of clinical studies

Most clinical studies performed on MP lacked histological biopsies. Generally, a biopsy is not justified due to the incidental asymptomatic nature of the disease in most patients. For the majority of patients, the diagnosis was based on the CT appearance and on follow-up CT studies that revealed no additional findings or changes [6].

Most of studies are retrospective and details regarding standardisation of CT scan protocol like intravenous contrast and oral contrast were not available.

Various aspects of interest are not included such as race/ethnicity, medications, chemotherapy and are not discussed in detail.

Discussion

Mesenteric panniculitis is a rare clinical entity that can occur independently or in association with other disorders. Diagnosis of this nonspecific, benign inflammatory disease presents a challenge to gastroenterologists, radiologists, surgeons, and pathologists.

In most cases, MP is self-limiting and regression can even be observed during follow-up in the absence of medical treatment. Clinical symptoms can subside without surgery and with the use of drugs such as corticosteroids, colchicine, cyclophosphamide, and tamoxifen. MP is considered not to be precancerous, and hence long-term follow-up is not needed [20].

There is a lot of dilemma clinicians facing regarding follow-up CT imaging in patients with mesenteric panniculitis. The clinicians should also not subject the patient to unnecessary imaging which also puts the patients at increased risk of radiation-induced gastrointestinal malignancies. The main dilemma clinicians face after diagnosis of MP is how to follow it up and what should be the frequency of scanning. As such CT remains the most widely used and cost-effective modality for adult patients. The frequency of scanning should be guided by clinical symptoms and aetiology of MP. For MP associated with benign causes and in asymptomatic patients, frequency of scanning can be less, unless there is change in clinical symptoms. It would be practically prudent to suggest yearly follow-up CT at first instance but we need clinical guidelines and clinical studies to support this.

Radiological imaging like magnetic resonance imaging may be a reasonable option but it may be expensive and ultrasound may not be the best modality as it can miss findings which CT scan can identify. Ultrasound and magnetic resonance imaging can be used as follow-up modalities for paediatric patients and patients with renal impairment.

Histopathological confirmation is usually not needed to establish the diagnosis of MP as radiological features often suffice. Biopsy should be reserved for cases where there is suspicion of associated malignancy, for example in a scenario where follow-up CT scans are showing progressively enlarging mesenteric nodes on the background of MP, hence raising suspicion of lymphoma. Wait and watch approach can be used for MP secondary to benign causes

Physicians should have a broad differential diagnosis when encountering a patient with mesenteric panniculitis and not subject the patient routinely to undergo CT-guided biopsy to establish the diagnosis.

Physicians should also not order multiple radiological investigations and still a conservative approach is needed. The challenges faced are whether an aggressive approach of surgical intervention is needed. But it would be worth watching and a holistic approach of wait and watch is desired.

At the moment, as per our literature review, we cannot find a confirmed certain link between mesenteric panniculitis and subsequent malignancy.

The prevalence of MP appears to be much higher than previously reported, and the reason for this is likely the major technological evolution in imaging during the last decade. This high prevalence may explain the spontaneous association with the numerous and probably unrelated clinical situations found in the literature. Finally, the vast majority of cases are considered idiopathic, benign, and asymptomatic [8]. Furthermore, referring clinicians are often unfamiliar with MP and therefore look-up to the reporting radiologist for management guidance [25].

Lymph node size (>12 mm) and the absence of the fat ring sign were identified as predictors of subsequent diagnosis of malignancy in patients with MP. Identification of MP via imaging should prompt awareness for possible malignancy in these patients [19].

High-quality research linking mesenteric panniculitis imaging features and subsequent malignancy is needed. The lack of consensus regarding the clinical significance of MP thus presents clinicians with a diagnostic dilemma, because MP is encountered frequently as an apparently incidental finding on cross-sectional imaging, usually abdomino-pelvic CT scan. There is no consensus on the treatment of MP. Treatment approaches in the literature mostly consist of supportive procedures intended to relieve the symptoms of MP. Physicians should apply holistic approach when they encounter mesenteric panniculitis which includes thorough physical examination, detailed history for red flag signs for malignancy and age-related appropriate screening for malignancy tailored to individual patients.