Malignancy Meets Mycobacterium: Diagnostic Dilemma in a Rare Coexistence of Rectal Adenocarcinoma and Tuberculosis

INTRODUCTION

Abdominal tuberculosis is the sixth most prevalent form of extrapulmonary tuberculosis, with the ileum and ileocecal region being the most affected sites, followed by the ascending colon in direct continuity with ileocecal involvement. Colonic tuberculosis is rare, accounting for only 2%–3% of abdominal tuberculosis cases.^[1] Within the colon, the rectum is an atypical site for tuberculosis, and its association with malignancy is even rarer. Isolated involvement of the colon and rectal tuberculosis is an exceedingly rare manifestation, with limited documented cases. The coexistence of rectal carcinoma with tuberculosis represents an atypical occurrence. Abdominal tuberculosis, though less prevalent than pulmonary disease, frequently presents with nonspecific clinical manifestations, resulting in delayed diagnosis and significant mortality.^[2] The diagnosis of this condition necessitates a high degree of clinical suspicion and specialised diagnostic procedures.^[3]

CASE REPORT

A 30-year-old male presented in the outpatient department with pain in the perianal region with associated discharge, intermittent low-grade fever, and watery, loose stools with blood streaks. He reported constitutional symptoms like loss of weight (around 15 kg) and loss of appetite for the past 3 months.

On examination, the patient appeared cachectic and dehydrated. Systemic examination revealed bilateral wheeze in all lung fields; per rectal examination showed multiple fistulae in the perianal region (>5 palpable) and induration of the perianal region with hard nodular growth felt in the lower rectum 5 cm above the anal verge. He denied any history of tuberculosis or contact with individuals with active tuberculosis. With a clinical presentation, a provisional diagnosis of disseminated tuberculosis was considered, prompting further investigation.

Magnetic resonance imaging (MRI) of the pelvis and abdomen revealed a T1 iso- to hypointense lesion measuring 8 (anteroposterior) × 6.7 (craniocaudal) × 6.2 cm (mediolateral) involving the lower rectum and anal canal. The lesion infiltrates the ischioanal fossa and the internal and external sphincter complex involving the puborectal with extension into the bilateral gluteal fat and the pelvic side wall show in Figure 1a. There is a fibrosed fistula tract seen extending from the lesion into the left gluteal region as in Figure 1b. Another fistulous tract is seen extending into the right gluteal region and another one into the root of the scrotum. Few mesorectal lymph nodes and multiple enlarged bilateral external iliac and inguinal lymph nodes were enlarged, with the largest measuring 3.1 × 2.4 cm in the right inguinal region show in Figure 1c and d.

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Figure 1:

(a) Axial T2-weighted magnetic resonance imaging (MRI) demonstrating a hypointense mass lesion involving the lower rectum with anterior infiltration into the root of the scrotum and corpora cavernosa (arrows). (b) Sagittal T2-weighted MRI image showing lesion infiltrating along the ischio-anal fossa, as well as involvement of the internal and external sphincter complex (arrow). (c) Axial T2-weighted MRI depicting infiltration of the lesion along the puborectalis muscle and surrounding the anal canal (arrow). (d) Coronal T2-weighted MRI outlining the hypointense lesion extension into the colon and significant luminal narrowing are seen with dilated large bowel loops (arrows).

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A CT-thorax showed a large, irregular, thick-walled air cavity noted in the right upper lobe communicating with subsegmental bronchi. Multifocal clusters of tree-in-bud centrilobular nodules and small patches of consolidation were noted in both lungs show in Figure 2. These findings are suggestive of pulmonary tuberculosis. Sputum GeneXpert was also positive.

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Figure 2:

Computed tomography-thorax. (a) Large irregular thick-walled cavity marked by arrow in the right upper lobe communicating with small wall calcifications. (b) Multiple smaller cavities with air-fluid level indicated by arrows in the right upper lobe. (c) Multifocal clusters of tree-in-bud centrilobular nodules and small patches of consolidations noted in both lungs indicated by arrows.

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Sputum bacterial culture grew Klebsiella pneumoniae, a superadded infection. The patient underwent sigmoidoscopy with biopsy. Endoscopic findings included lipid-laden stools, multiple anal fistulae with warty anal lesions and nodular lesions in the anal canal and rectum. Biopsies were taken from multiple sites for histopathologic examination (HPE) and tissue GeneXpert testing. The HPE report revealed adenocarcinomatous changes with mitotic activity and chronic inflammatory fibrosis found within the lesion show in Figure 3. The tissue samples from both the lesion and fistula tract were positive for GeneXpert. Hence, the patient was initiated on anti-tuberculosis therapy (ATT).

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Figure 3:

(a) Adenomatous changes found along with normal rectal tissue. High mitotic activity; neoplasm infiltrating the lamina propria and focally smooth muscle fibres in glandular pattern, cribriform pattern and clusters. This is in correlation with adenocarcinoma grade 2 (arrow) haematoxylin and eosin with 10x magnification. (b) The tumour cells show moderate eosinophilic cytoplasm (arrow) haematoxylin and eosin with 40x magnification, a high Nucleus:Cytoplasm (N:C) ratio, moderate pleomorphic mitotically active nuclei, condensed chromatin, and conspicuous nucleoli. (c) There is desmoplasia and moderate lymphoplasmacytic haematoxylin and eosin with 100x magnification infiltrate (arrow) haematoxylin and eosin with 40x magnification. (d) There are neoplastic cells with infiltrating neutrophils in the lamina (arrows).

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The patient was clearly made to understand the diagnosis, and the course of management was clearly explained. He was initiated on chemotherapy with the FOLFOX regimen (folinic acid (leucovorin), 5-fluorouracil (5-FU) and oxaliplatin (L-OHP)). The carcinoembryonic antigen (CEA) biomarker was used for prognostic value, where his initial baseline was 102 ng/ml and gradually declined to 6.6 ng/ml over 10 months. His repeat imaging showed no notable change in tumour size over 10 months. He was initiated on aggressive chemotherapy that included intravenous oxalplatin 114 mg, leucovorin 270 mg, and 5-FU 540 mg with 5-FU 800 mg infusion (FOLFOX regimen). This regimen was carried out for eight cycles, along with external beam radiotherapy at 45–50 Gy in 25–27 fractions. Post-chemotherapy, Positron emission tomography (PET)-CT showed no significant change in the size of the lesion. With proper guideline indications, he was initiated on targeted therapy—intravenous Bevacizumab 400 mg (5 mg/kg) over 90 minutes every 2 weeks. He completed two cycles of targeted therapy, following which he was lost in follow-up.

DISCUSSION

Colonic tuberculosis is a rare form of extrapulmonary tuberculosis, with an incidence of 3%–4% of all abdominal tuberculosis. Among all abdominal tuberculosis, the colon is an uncommon site, with the rectum being even rarer. A retrospective study carried out from 2006 to 2010 of abdominal tuberculosis showed an incidence rate of 28 in 100,000 population^[4] with a slight male predominance.

Anal tuberculosis is uncommon and has a distinct clinical presentation with multiple tubercular fistulae and a rectal mass. This case had 5–6 palpable fistulae, which raised the suspicion of rectal tuberculosis. As reported by Dandapat et al.^[5] a well-documented correlation exists between multiple anal fistulae and rectal tuberculosis, with an association detected in 80%–91% of cases. There is no particular sign or examination finding that distinguishes a tuberculous fistula from a cryptoglandular fistula. This made us have a clinical suspicion of rectal tuberculosis in this case.

Chronic tuberculosis forming an eccentric rectal mass and multiple fistulae in the anal canal is a documented pathology described in Dhungel B et al.^[6] A descriptive study conducted in a south Indian hospital between 2014 and 2016 documented various clinical presentations and complications of abdominal tuberculosis.^[5]

Imaging studies also demonstrated abnormalities that supported the dual pathology hypothesis, with MRI demonstrating local rectal involvement while CT confirmed systemic tuberculous disease. A 2-year cohort study in South India reported 11 patients with co-existing tuberculosis and malignancy, of which nine cases were adenocarcinoma and two were squamous cell carcinoma.^[7]

The pathogenesis of tuberculosis-associated carcinogenesis involves several interconnected pathways. First, chronic tuberculous infection leads to oxidative deoxyribo nucleic acid (DNA) damage and genomic instability. Second, Mycobacterium tuberculosis has been shown to exploit host DNA repair mechanisms, with secreted virulence factors directly inhibiting DNA repair processes. Third, the chronic inflammatory process promotes epithelial-to-mesenchymal transition and triggers the dysplasia-carcinoma sequence through persistent tissue damage and aberrant repair responses. The coexistence of tuberculosis and malignancy may follow two pathways: tuberculosis-induced carcinogenesis and, secondly, a malignancy-facilitated tuberculous superinfection.^[8,9] Supporting the hypothesis, Chakaravatty et al. have reported that chronic inflammatory damage from colonic tuberculosis can lead to a sequence of metaplasia and dysplasia ultimately ending in neoplastic transformation.^[10]

Histopathological study in this case has clear adenomatous changes in the tissues with few scattered granulomas, confirming the coexistence of dual pathology. Chaudary et al.^[11] documented a retrospective cohort study of the past 12 years, reporting seven patients with coexisting colon adenocarcinoma and tuberculosis. Many published articles have reported colon tuberculosis that mimics colon carcinoma. Moreover, nonspecific clinical symptoms create a diagnostic dilemma to differentiate between other intestinal diseases.^[11]

In abdominal tuberculosis, granulomas are more numerous, larger (more than 200 μm), and coalescent in the mucosa and submucosa than in other infected tissues. However, caseating necrosis has a variable pattern in tuberculous abdominal tissues. Caseating necrosis has been reported in nearly half of the intestinal granulomas, according to the published literature. The biopsy specimen in this case demonstrated varying morphology within the affected tissues, with scattered granulomas and overlapping adenomatous changes. These findings support the hypothesis that either tuberculosis or malignancy may have been the primary pathological processes. A study by Ramamoorthy et al. confirmed that due to neoplastic dominance, the underlying tubercular granuloma could be missed.^[7,11]

Multiple factors may have been involved in the initiation and development of disease pathology. Given the challenges associated with early diagnosis and the complexity of treatment protocols involving prolonged antituberculous therapy and chemotherapy, this patient required frequent monitoring intervals. Due to potential unknown interactions between ATT and the FOLFOX regimen, surveillance for unexpected adverse drug reactions was essential, in addition to monitoring for known adverse effects.^[12]

In 12 months of follow-up, CEA decreased from 102 to 6.6 ng/ml. Post-ATT, his three consecutive GeneXpert tests were negative. Post-neoadjuvant chemotherapy with the FOLFOX regimen, his follow-up imaging showed no reduction in tumour size. The patient was counselled on the need for surgical resection with colostomy diversion. The patient did not give consent for surgery, and he did not come for further follow-up.

CONCLUSION

Coexistent rectal adenocarcinoma and rectal tuberculosis are rare, requiring a high index of suspicion for diagnosis. Management is challenging and demands a multidisciplinary approach with close monitoring. Avoiding the coincident adverse effects of different treatment approaches for each disease was difficult. Additionally, this case emphasises the critical role of long-term follow-up in identifying and managing recurrences. More cases must be illustrated, structured, debated, and comprehended to create a clear-cut treatment plan and a better understanding of the pathophysiology of the double-edged sword.