Not all colonic growths are malignant

Abstract

We present the case of a 34-year-old woman who was diagnosed to have adenocarcinoma of the caecum based on the clinical, radiological, histopathological and intraoperative findings. However, postoperative histopathology showed only features of xanthogranulomatous inflammation without any evidence of malignancy. This benign chronic inflammatory condition could present as a histological surprise. It is important for both surgeons and pathologists alike to be aware of this.

Background

Xanthogranulomatous inflammation (XGI) of the appendix is a rare presentation. Of the 14 cases reported in literature, there were 8 cases involving the appendix,¹ 2 involving terminal ileum,² 2 involving the sigmoid colon,^{2 3} 1 involving caecum⁴ and 1 involving ascending colon.⁵ It mimics infiltrative malignancy in clinical, radiological and pathological presentation.

Case presentation

A 34-year-old woman presented with complaints of acute onset, severe, non-colicky pain in the right lower abdomen for 3 months. She had history of multiple episodes of non-bilious vomiting and loose stools which lasted for the initial 2 weeks. The pain was initially intermittent but later became continuous with decrease in intensity over 3 months. There was no history suggestive of gastrointestinal bleeding. There was no history of loss of weight or appetite, fever, jaundice, abdominal distension or constipation. She did not have any other co-morbid illnesses or prior contact with tuberculosis. On examination, there was tenderness in the right iliac fossa on deep palpation.

There were no other significant findings on examination.

Investigations

Her preoperative blood investigations were as follows: haemoglobin 116 g/L, total leucocyte count 6.1x10⁹/L, platelets 248x10⁹/L, serum albumin 4.5 g/dL, serum creatinine 0.55 mg%, carcinoembryonic antigen (CEA) 2.21 IU/L.

The patient had initially presented to another centre, where she underwent evaluation including imaging, colonoscopy and biopsy. A non-contrast CT of the abdomen had been performed which did not show any obvious features of a phlegmon or an abscess. Colonoscopy had revealed an ulcer in the ascending colon with elevated margins and biopsy from the ulcer was reported as signet ring cell adenocarcinoma. A review of the slides at our centre was suggestive of poorly differentiated adenocarcinoma with atypical cells showing hyperchromatic pleomorphic nuclei.

A contrast-enhanced CT scan of the abdomen and pelvis showed mural thickening along the posterior wall of the caecum with no extramural disease (figure 1). It also showed an appendicolith with minimal peri-appendiceal fat stranding.

Figure 1.

Axial section of CT scan showing thickening of the posterior wall of caecum with no extramural extension.

Differential diagnosis

Clinical features of abdominal pain with altered bowel habits suggested a probable bowel origin of the symptoms. Right lower quadrant tenderness raised suspicion of ileocaecal involvement. Possible aetiologies thought of earlier were malignancy (either lymphoma or carcinoma) and infection (ileocaecal tuberculosis). Slide review of the biopsy brought us to a working diagnosis.

Treatment

The case was discussed in a multidisciplinary tumour board meeting where it was decided to proceed with upfront resection. She underwent radical right hemicolectomy. Intraoperatively, a growth was noted in the caecum which was fixed to the parietal wall. The caecum was surrounded with dense adhesions and fibrosis.

Outcome and follow-up

Her postoperative period was uneventful and she was discharged in a stable condition.

Gross examination of the right hemicolectomy specimen revealed a 4x4x3 cm appendicular mass. The ileal and caecal mucosa were normal. The wall of the appendix appeared markedly thickened with multiple yellow white foci on the external surface. Mesenteric fat had multiple lymph nodes, with a tan cut surface.

Microscopic examination of the mass showed sections of the appendix with submucosal fibrosis with dense infiltrates of lymphocytes, plasma cells, eosinophils, neutrophils and histiocytes including foamy histiocytes forming aggregates with multinucleate giant cells—appendicular perforation with XGI.

The initial mucosal biopsy slides were reviewed again in view of the new development and were found to be consistent with XGI. The case was discussed in multidisciplinary tumour board and it was decided to keep her on follow-up with no further intervention at this point.

She was asymptomatic and radiologically disease-free at a 3-month follow-up visit.

Discussion

First reported by Oberling in 1935, XGI is a rare form of chronic inflammation that can affect almost any organ system in the body.⁶ It is usually secondary to chronic inflammation, necrosis and haemorrhage.^{2 7} The process is most commonly seen in kidney and gall bladder, but is also found to affect the endometrium, pelvis, lymph nodes, skin, thyroid and bones.^{4 8} The literature on involvement of the gastrointestinal tract has been limited mostly to case reports and a few case series.1–5 8–10 Almost all the reported cases were diagnosed postoperatively, after the patient had undergone radical resection for infiltrative carcinoma.2 3 5 11 12

Similar to our case, most cases present with a history of abdominal pain, sometimes accompanied by features of intestinal obstruction. The age at presentation was widely varied, ranging from 2 years to 72 years.^{1 5} Anaemia may be seen, but it was not present in our patient.⁴ It often presents as a mass due to extensive inflammation and fibrosis, and this can often be mistaken as malignant infiltration intraoperatively and on cross-sectional imaging.⁵ In our case, there was bowel wall thickening seen on contrast-enhanced CT and intraoperatively there was a growth in the caecum which was fixed to the parietal wall. On mucosal biopsy specimens, it is easy to mistake the foamy macrophages of XGI for atypical cells with hyperchromatic pleomorphic nuclei (figure 2). Pathological differential diagnoses could also include malakoplakia or localised xanthomatous deposits with foam cell features.²

Figure 2.

Histopathology image at 20x showing atypical cells with hyperchromatic pleomorphic nuclei (black arrowheads).

Though the pathological features are well-defined, the pathogenesis is still subject to debate. The localised proliferation of lipid laden foamy histiocytes in XGI is believed to represent chronic suppurative inflammation secondary to interaction between the host and microorganisms. It occurs in the settings of recurrent infection, obstruction, immunological disorders and defective lipid transport. Examples of immunological disorders include disrupted chemotaxis of polymorphs and macrophages, which is a specific immune response towards Proteus and Escherichia infections.² In our case, the initial incident might have been an episode of acute appendicitis with perforation. It must have self-contained and was managed conservatively. It could have triggered off a cascade that has gone on to become smouldering chronic inflammation leading to the current presentation. The proof for this theory can be found in the case series by Guo and Greenson, where they studied 22 cases of interval appendicectomy and found that 8 of them had XGI. In the 44 controls who had acute appendicectomy, none of them had XGI. This is suggestive of the fact that XGI is a result of chronic infection and inflammation.¹

The condition is benign and is managed only by surgical excision. However, it is important to do oncologically sound operations. Though one might argue that such radical resection is not called for in a benign condition, it is to be noted that histological markers and expertise may not be readily available in resource-poor settings. Confirmation of the benign nature on the postoperative histopathology will come as a histological surprise to the surgeon and a welcome relief to the patient.

Learning points.

• Xanthogranulomatous inflammation is a type of chronic inflammation that can mimic malignancy on clinical examination, imaging and histology.

• This condition warrants a surgical resection in symptomatic patients.

• Confirmation of the diagnosis can come as a histological surprise to the surgeon and a welcome relief to the patient.