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TB or not TB: A comprehensive review of imaging manifestations of abdominal tuberculosis and its mimics

Open AccessPublished:February 09, 2021DOI:https://doi.org/10.1016/j.clinimag.2021.02.012

      Highlights

      • TB is a major health concern worldwide given its ever-increasing prevalence.
      • Abdominal TB is the most common site of extra-pulmonary tuberculosis infection.
      • Imaging features of abdominal TB may mimic a variety of other diseases.
      • Timely initiation of therapy is central to reducing related morbidity and mortality.

      Abstract

      The ever-growing prevalence of tuberculosis is a cause for concern among both developing and developed countries. Abdominal tuberculosis is the most common site of extrapulmonary tuberculosis and involves almost all of the visceral organs. Clinical presentation of abdominal tuberculosis is often non-specific. Thus, having a high index of clinical suspicion is necessary to aide early diagnosis and guide prompt initiation of appropriate treatment. In this review, we focus on the entire spectrum of abdominal tuberculosis and other diseases mimicking it with an emphasis on their imaging findings.

      Abbreviations:

      TB (tuberculosis), HIV (human immunodeficiency virus), TNF (tumor necrosis factor), GI (gastrointestinal), GU (genitourinary), ADA (adenosine deaminase), AFB (acid-fast bacillus), NAAT (nucleic acid amplification test), SAAG (serum-ascites albumin gap), TST (tuberculin skin test), IGRA (interferon-gamma release assays), PCR (polymerase chain reaction)

      Keywords

      1. Introduction

      In 2018, tuberculosis (TB) affected an estimated 10 million people worldwide, the majority of which were from developing countries.
      • Geneva: World Health Organization
      Global tuberculosis report 2019.
      Tuberculosis poses a major health concern in not only developing countries but also developed countries due to the impact of globalization and emigration, and the association of TB with human immunodeficiency virus (HIV) infection.
      • Stojkovic M.
      • et al.
      Radiological diagnoses in the context of emigration: infectious diseases.
      Abdominal involvement is the most common extrapulmonary manifestation of TB, accounting for about 5% of all tuberculosis cases worldwide.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      • Sharma S.K.
      • Mohan A.
      Extrapulmonary tuberculosis.
      • Rathi P.
      • Gambhire P.
      Abdominal Tuberculosis.
      Abdominal tuberculosis may involve the lymph nodes, gastrointestinal system, peritoneum, and solid organs. It can occur as a consequence of reactivation of latent tuberculosis, ingestion of Mycobacterium tuberculosis (via infected lung secretions, unpasteurized dairy products or undercooked meats), hematogenous spread from an adjacent focus, or through infected lymphatic channels and nodes.
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      Risk factors for developing abdominal TB include underlying medical conditions such as cirrhosis, diabetes mellitus, HIV infection, renal insufficiency, and malignancy; medical treatment with steroids and anti-tumor necrosis factor (TNF) agents; and others such as malnutrition, tobacco smoking, intravenous drug use and alcoholism.
      • Sharma S.K.
      • Mohan A.
      Extrapulmonary tuberculosis.
      ,
      • Figueiredo A.A.
      • et al.
      Epidemiology of urogenital tuberculosis worldwide.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      • Peto H.M.
      • et al.
      Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006.
      • Shafer R.W.
      • et al.
      Extrapulmonary tuberculosis in patients with human immunodeficiency virus infection.
      • Thoeni R.F.
      • Margulis A.R.
      Gastrointestinal tuberculosis.
      • Thwaites G.
      40 - tuberculosis.
      In general, clinical features are non-specific and may include fever, weight loss, abdominal/back pain, ascites, diarrhea, abdominal mass, bowel obstruction, and hematuria. A high index of suspicion is required to allow for early diagnosis and prompt initiation of therapy. In this review, we discuss and illustrate the clinical and radiologic features of abdominal tuberculosis and other diseases mimicking it (Table 1), and briefly discuss the management and treatment of these patients.
      Table 1Summary of clinical imaging findings and key differential diagnoses of the spectrum of abdominal tuberculosis.
      DiagnosisImaging findingsDifferential diagnosis
      Tuberculous lymphadenitisUS

      Enlarged hypoechoic nodes (± matted appearance) or hyperechoic nodes with posterior shadowing (due to calcifications)

      CT

      First stage: Homogenous enhancement

      Second stage: Central caseous necrosis and peripheral rim enhancement

      Final stage: Fibrosis and calcifications
      • Nonseminomatous germ cell cancer
      • Lymphoma
      • Metastatic nodes
      • Fungal infections
      • Celiac disease
      Gastrointestinal tuberculosisEsophagusEndoscopic US

      Asymmetric wall thickening with loss of wall stratification, mucosal ulceration and adjacent LAD

      CT

      Irregular diffuse wall thickening, fistulous tracts, diverticula, or strictures with LAD
      • Esophageal cancer
      Stomach & duodenumCT

      Irregular diffuse wall thickening (most commonly at the antrum and distal body) with ulceration, fibrosis, sinus and fistula tracts (rare) and LAD
      • Gastric scirrhous adenocarcinoma
      • Pancreatic cancer of the head
      • Metastatic disease
      • Chron's disease
      • Infectious causes (syphilis)
      Small intestine & colonCT

      Diffuse wall thickening of affected segment (predominantly in the terminal ileum and cecum) with surrounding fat stranding and LAD
      • Primary cecal malignancy
      • Chron's disease
      • Backwash ileitis (from ulcerative colitis)
      • Infectious causes (Yesinia and amebiasis)
      Hepatosplenic tuberculosisUS

      Multiple variable size hypoechoic lesions

      Late stage: calcifications

      CT

      Multiple variable size hypodense lesions with central or peripheral post-contrast enhancement, LAD, ascites and peritonitis

      Late stage: Calcifications

      MRI

      Multiple variable size lesions with T1-weighted hypointense and T2-weighted isointense to hyperintense signal showing diffusion restriction with central or peripheral post-contrast enhancement, LAD, ascites and peritonitis
      • Primary malignancy
      • Pyogenic abscess
      • Metastasis
      • Fungal infections (Candida, Aspergillus)
      Genitourinary tuberculosisKidneyCT

      Early: Focal hypo-perfusion on contrast-imaging

      Late: Multiple strictures resulting in uneven caliectasis

      Healed/chronic: Renal atrophy, progressive hydronephrosis, and dystrophic calcifications (“putty kidney”)
      • Transitional cell/squamous cell carcinoma
      • Medullary sponge kidney
      • Papillary necrosis
      • Chronic pyelonephritis
      UreterCT

      Early: Irregular thickening of the ureteric wall with luminal narrowing and periureteric inflammatory changes

      Late: Strictures, ulceration and fibrosis leading to a corkscrew ureter and proximal hydroureteronephrosis

      Chronic: Pipe-stem ureter and foreshortening of ureter
      • Ureteral stones
      • Infectious causes (schistosomiasis)
      BladderCT

      Early: Shrunken bladder with wall thickening and surrounding fat stranding

      Late: Thimble bladder due to chronic scarring, calcifications (rare)
      • Transitional cell carcinoma
      • Post-radiation cystitis
      • Chemotherapy (cyclophosphamide)
      • Infectious causes (schistosomiasis)
      Genitourinary tuberculosisOvariesUS, CT and MRI

      Enlarged heterogenous ovaries with associated ascites and regional LAD
      • Ovarian carcinoma
      Fallopian tubesUS, CT and MRI

      Multifocal constrictions and scarring resulting in a “beaded” appearance with hydro/pyosalpinx
      • Salpingitis isthmica nodosa
      • Fallopian tube endometriosis
      Testis & epididymisUS

      Diffuse enlargement with heterogenous echotexture with increased vascularity or heterogenous ill-defined hypoechoic testicular lesion

      MRI

      Low signal intensity in T2-weighted sequence
      • Bacterial epididymitis
      ProstateUS

      Hypoechogenicity and increased vascularity

      MRI

      Diffuse, radiating area with streaky low signal intensity on T2-weighted MRI (watermelon skin) or an enlarged heterogeneous prostate with small abscesses

      Chronic: Diffuse dystrophic calcifications
      • Prostate carcinoma
      Tuberculous peritonitisCT

      Wet: Free or loculated ascites with nodular peritoneal enhancement and omental caking

      Fibrotic: Omental thickening and omental caking, fixed bowel loops, matted bowel and mesentery ± loculated ascites, abdominal cocoon/encapsulating peritoneal sclerosis (late stage)

      Dry: Fibrous adhesions of bowel loops, mesenteric thickening, and caseous mesenteric lymphadenopathy
      • Disseminated peritoneal carcinomatosis
      • Ovarian carcinoma
      • Peritoneal mesothelioma
      • Non-tuberculous peritonitis
      Tuberculous abscessCT and MRI

      Multiloculated peripherally enhancing abscess with surrounding fat stranding and peripherally enhancing necrotic LAD and foci of calcifications
      • Soft tissue tumors
      • Tuberculoma
      • Fungal infections
      Abbreviations: LAD = lymphadenopathy.

      2. Tuberculous lymphadenitis

      Tuberculous infection and inflammation of the lymph nodes, called tuberculous lymphadenitis, is the most common presentation of abdominal TB presenting in 55–66% of cases.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      ,
      • Mert A.
      • et al.
      Tuberculous lymphadenopathy in adults: a review of 35 cases.
      ,
      • Salvador F.
      • et al.
      Epidemiology and diagnosis of tuberculous lymphadenitis in a tuberculosis low-burden country.
      Tuberculous lymphadenitis occurs more commonly in females than males and immigrants from endemic countries with an age range of 30–40 years old.
      • Salvador F.
      • et al.
      Epidemiology and diagnosis of tuberculous lymphadenitis in a tuberculosis low-burden country.
      ,
      • Fontanilla J.M.
      • Barnes A.
      • von Reyn C.F.
      Current diagnosis and management of peripheral tuberculous lymphadenitis.
      The cervical lymph nodes are the most commonly involved group due to its proximity to the lung parenchyma.
      • Peto H.M.
      • et al.
      Epidemiology of extrapulmonary tuberculosis in the United States, 1993-2006.
      ,
      • Mathiasen V.D.
      • et al.
      Epidemiology of tuberculous lymphadenitis in Denmark: a nationwide register-based study.
      Approximately 5.7–17.2% of cases with peripheral tuberculous lymphadenopathy also have involvement of abdominal lymph nodes.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      ,
      • Mert A.
      • et al.
      Tuberculous lymphadenopathy in adults: a review of 35 cases.
      ,
      • Salvador F.
      • et al.
      Epidemiology and diagnosis of tuberculous lymphadenitis in a tuberculosis low-burden country.
      The most frequently involved abdominal group of lymph nodes are omental, mesenteric, and peripancreatic lymph nodes.
      • De Backer A.I.
      • et al.
      Abdominal tuberculous lymphadenopathy: MRI features.
      • Yang Z.G.
      • et al.
      Tuberculosis versus lymphomas in the abdominal lymph nodes: evaluation with contrast-enhanced CT.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      Clinical presentation of abdominal tuberculous lymphadenitis in additional to constitutional symptoms are based on the site of lymphadenopathy and include abdominal pain, acute abdomen, jaundice, portal vein thrombosis and portal hypertension, renovascular hypertension, fistula formation, duodenal stricture and stenosis.
      • De Backer A.I.
      • et al.
      Abdominal tuberculous lymphadenopathy: MRI features.
      ,
      • Konishi H.
      • et al.
      A case of tuberculous mesenteric lymphadenitis and peritonitis with symptoms of acute abdomen.
      • Caroli-Bosc F.X.
      • et al.
      Abdominal tuberculosis involving hepatic hilar lymph nodes. A cause of portal vein thrombosis and portal hypertension.
      • Puri S.
      • Khurana S.B.
      • Malhotra S.
      Tuberculous abdominal lymphadenopathy causing reversible renovascular hypertension.
      Tuberculous lymphadenitis progresses through different stages which can be reflected on CT imaging. The first stage of lymphoid proliferation is marked by lymph node enlargement with homogenous enhancement. With disease progression, the central part of the lymph node undergoes caseous necrosis resulting in a centrally non-enhancing node with peripheral capsular rim-enhancement (Fig. 1). Capsular degeneration results in the fusion of adjacent lymph nodes which appear as a multilocular enhancement. In the final stage, after treatment or healing, the lymph nodes undergo fibrosis, and calcifications can be seen (refer to Fig. 5).
      • Zhang G.
      • et al.
      Differentiation between tuberculosis and leukemia in abdominal and pelvic lymph nodes: evaluation with contrast-enhanced multidetector computed tomography.
      Lymph node enlargement in tuberculous lymphadenitis often demonstrates self-limited growth, with a range of 12–40 mm.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      TB lymphadenitis can also be seen on ultrasonography as round or ovoid enlarged lymph nodes with a central hypoechoic area that may be matted.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Fig. 1
      Fig. 1Tuberculous lymphadenitis. Contrast-enhanced CT demonstrates multiple A) mediastinal, B) retrocrural, C) mesenteric/omental (arrow) and retroperitoneal (arrowhead) necrotic lymph nodes with peripheral capsular rim-enhancement and low central density. A small right-sided pleural effusion is also seen in image A.
      The radiological differential for the appearance of abdominal tuberculous lymphadenitis includes malignancies such as nonseminomatous germ cell tumor, pancreatic cancer, lymphoma, and metastatic lymph nodes.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Koh D.M.
      • Hughes M.
      • Husband J.E.
      Cross-sectional imaging of nodal metastases in the abdomen and pelvis.
      In addition, fungal infections and celiac disease can also have a similar appearance.
      • Paño B.
      • et al.
      Pathways of lymphatic spread in gynecologic malignancies.

      3. Gastrointestinal tuberculosis

      Gastrointestinal (GI) TB is a rare manifestation of abdominal TB and is the sixth most common form of extrapulmonary TB.
      • Malikowski T.
      • et al.
      Tuberculosis of the gastrointestinal tract and associated viscera.
      It can affect any part of the GI tract starting from the esophagus to the rectum. The three main forms of GI TB are (i) ulcerative type (60%), which is characterized by single or multiple mucosal ulcerations commonly affecting the jejunum and ileum, (ii) ulcero-hypertrophic type (30%), which is characterized by thickening and ulceration of intestinal wall, and (iii) hypertrophic type (10%), which is characterized by scarring and fibrosis commonly affecting the ileum and cecum.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      Complications of the three forms are similar and may include intestinal perforation, bleeding and fistula formation.
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      ,
      • Malikowski T.
      • et al.
      Tuberculosis of the gastrointestinal tract and associated viscera.
      Bowel obstruction may also occur as a result of mechanical obstruction secondary to stricture formation or intestinal hypertrophy.
      • Ha H.K.
      • et al.
      Intestinal tuberculosis with abdominal complications: radiologic and pathologic features.

      3.1 Esophagus

      Esophageal TB is very rare and is the least common site of TB involvement in the gastrointestinal tract seen in only 0.2–1% of cases.
      • Rathi P.
      • Gambhire P.
      Abdominal Tuberculosis.
      ,
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      It occurs due to the spread of infection from either the lungs, spine or infected mediastinal nodes at the level of the carina.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      Esophageal involvement often manifests due to extrinsic compression from the lymphadenopathy resulting in either compression or narrowing of the esophagus.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      In addition to constitutional symptoms, dysphagia and retrosternal pain may be present.
      • Thwaites G.
      40 - tuberculosis.
      ,
      • Nagi B.
      • et al.
      Imaging of esophageal tuberculosis: a review of 23 cases.
      ,
      • Sharma V.
      • et al.
      Primary esophageal tuberculosis mimicking esophageal cancer with vascular involvement.
      Common radiologic findings include irregular wall thickening, mucosal ulceration, fistula formation, and traction diverticula and strictures as a result of chronic fibrotic changes (Fig. 2).
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      This ulceration can mimic esophageal malignancy with mucosal nodularity on barium imaging. CT imaging is more helpful in delineating tuberculous lymphadenopathy from the displaced esophagus and the extent of fistulous tracts.
      • Williford M.E.
      • et al.
      Esophageal tuberculosis: findings on barium swallow and computed tomography.
      Endoscopic ultrasound may show asymmetric esophageal wall thickening with loss of wall stratification.
      • Sharma V.
      • et al.
      Primary esophageal tuberculosis mimicking esophageal cancer with vascular involvement.
      Fig. 2
      Fig. 2Esophageal tuberculosis. A low-density heterogenous soft tissue mass (arrowhead) involving the mid-thoracic esophagus is seen, which was formed possibly from the conglomeration of irregular esophageal wall thickening and paraesophageal lymphadenopathy. Multiple enlarged and matted medistinal lymph nodes with central necrosis are seen (asterisk).

      3.2 Stomach

      Gastric involvement with TB is rare and seen in 0.4%–2% of cases
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      generally affecting the antrum and distal body.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Symptoms of gastric involvement include vague epigastric discomfort and upper GI bleeding. Nausea and vomiting may occur in the presence of gastric outlet obstruction secondary to antral narrowing. CT imaging can show the late-stage hypertrophic features of tuberculous pyloric stenosis.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      The presence of sinus tract and fistula is rare but suggestive of tuberculosis. The most commonly involved parts are the gastric antrum and distal body. On imaging, the hypertrophic form can show severe and diffuse wall thickening (Fig. 3). Ulceration and fibrosis can lead to antral narrowing. Rarely, fistula and sinus tracts also occur in gastric TB.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Fig. 3
      Fig. 3Gastric tuberculosis. A and B) Contrast-enhanced CT demonstrates diffuse irregular thickening of the antrum of the stomach with surrounding fat stranding. Mild proximal dilation of stomach could be suggestive for gastric outlet obstruction. Small multi-loculated abscess is identified in the left lobe of the liver. C) T1-weighted MRI redemonstrates the diffuse irregular thickening of the gastric wall with surrounding inflammatory changes, D) diffusion restriction and E) post-contrast enhancement.
      The radiological differential for the appearance of gastric TB includes malignancies such as gastric scirrhous adenocarcinoma, gastrointestinal stromal tumor, lymphoma and metastatic disease (lung, breast, pancreas), and other causes such as syphilis, sarcoidosis, peptic ulcer disease and Chron's disease.
      • Chaudhary P.
      • et al.
      Gastric tuberculosis.
      • Kim S.-E.
      • et al.
      A case of gastric tuberculosis mimicking advanced gastric cancer.
      • Park J.J.
      • Cheon J.H.
      Differential diagnosis: intestinal tuberculosis.
      • Baldwin M.
      • et al.
      Part 1-classic signs in gastrointestinal radiology.

      3.3 Duodenum

      Duodenal TB is uncommon and seen in 2–2.5% of cases of TB with GI involvement. The involvement of the C-loop of the duodenum occurs due to contiguous invasion or extrinsic compression from adjacent lymph nodes.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Patients may present with obstructive or dyspeptic symptoms, with the former being more common. The duodenum is most commonly affected by extrinsic compression from adjacent lymphadenopathy resulting in obstruction and can be easily demonstrated on CT scan. Duodenum may also demonstrate intrinsic hypertrophic involvement which can be seen on CT as thickening of the duodenal walls. Ulceration can lead to strictures and fistulae, which are seen clearly on barium studies.
      • Nagi B.
      • et al.
      Radiological findings in duodenal tuberculosis: a 15-year experience.
      The radiological differential for the appearance of duodenal TB includes superior mesenteric artery syndrome, atypical peptic ulcer disease, Chron's disease and malignancies such as lymphoma and pancreatic carcinoma of the head.
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.

      3.4 Jejunum and ileum

      The ileocecal region is the most common site of involvement in GI TB seen in 80–90% of cases.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      An abundance of lymphoid tissue and an increased rate of absorption may predispose this site for TB involvement.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      The involvement of the rest of the small bowel is infrequent and usually occurs together with peritonitis.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Clinical symptoms include colicky abdominal pain, weight loss and anemia, and complications due to intestinal obstruction, perforation and hemorrhage may also occur.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      Early stages of ileocecal TB are marked by mild mural thickening of the ileum and cecum. Late stages can show eccentric mural thickening involving the medial cecal wall and the valve, with regional lymphadenopathy and inflammatory changes.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      These findings are easily demonstrated on CT imaging (Fig. 4). The earliest sign on barium studies is hypermobility and spasm of the ileocecal valve with associated edema. Barium studies can also show a narrowed terminal ileum with a gaping, incompetent ileocecal valve (Fleischner sign) or rapid emptying of the diseased segment through the incompetent valve from a narrowed terminal ileum to a rigid and shortened cecum (Stierlin sign).
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      More advanced stages can show a conical cecum, with a shrunken and retracted cecum out of the right iliac fossa due to fibrosis of the mesocolon (Fig. 5).
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      Fig. 4
      Fig. 4Jejunal and ileal tuberculosis. A) Contrast-enhanced CT demonstrates diffuse jejunal and ileal thickening (arrow) as well as a few tiny extraluminal air bubbles (asterisk) which indicate micro perforation. Omental nodularity (arrowhead) and mesenteric fat stranding (arrow) are also evident in image B.
      Fig. 5
      Fig. 5Ileocecal tuberculosis (late stage). A and B) Contrast-enhanced CT demonstrates a deformed ileocecal junction with a conical cecum (white arrow) and a shrunken right colon with a stricture (arrowhead) at the hepatic flexure and proximal dilation (red arrow). Terminal ileum is marked by the blue arrow. C, D and E) Multiple calcified mesenteric and omental lymph nodes are also seen (circles). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
      The radiological differential for the appearance of jejunal and ileal TB includes infectious causes such as amebiasis and infection caused by Salmonella and Yersinia; inflammatory causes such as Crohn's disease and ulcerative colitis causing backwash ileitis, and malignancy such as primary cecal malignancy.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Thoeni R.F.
      • Cello J.P.
      CT imaging of colitis.
      ,
      • Elsayes K.M.
      • et al.
      CT enterography: principles, trends, and interpretation of findings.

      3.5 Appendix

      Isolated involvement of TB in the appendix is rare and accounts for only 0.08% of all appendectomy specimens.
      • Chong V.H.
      • et al.
      Tuberculous appendix: a review of clinical presentations and outcomes.
      Clinical presentation can be similar to that of acute appendicitis. However, contiguous involvement of the ileocecal region on imaging would be more suggestive of TB involvement.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      An appendiceal mass mimicking malignancy may also be seen.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.

      3.6 Colon

      Colorectal TB is seen in about 10% of gastrointestinal TB cases without small intestine involvement.
      • Thoeni R.F.
      • Margulis A.R.
      Gastrointestinal tuberculosis.
      ,
      • Nagi B.
      • et al.
      Colorectal tuberculosis.
      The cecum is the most commonly involved site in colorectal TB, with concomitant involvement of the ileocecal valve and terminal ileum.
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      Aside from the cecum, the transverse colon, rectum, and ascending colon have been reported to be the commonest sites of involvement in colorectal TB.
      • Nagi B.
      • et al.
      Colorectal tuberculosis.
      Clinical features include abdominal pain, weight loss and change in bowel habits. Bowel wall perforations and fistulas are seen in up to 18.9% of cases. Localized abscess formation may also be seen with GI tract involvement.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      Colonoscopy in the setting of colorectal TB shows linear or fissured ulcers (which may be transverse or circumferential) covered with exudates. These ulcers are surrounded by abnormal mucosa (erythema, edema, and/or nodularity), which is in contrast to normal-appearing mucosa surrounding the ulcers in Crohn's disease. The most common findings on CT scans in colonic TB in decreasing order of frequency are strictures, features of colitis, and polypoid lesions
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      in addition to those seen with jejunal and ileal TB (Fig. 6).
      Fig. 6
      Fig. 6Cecal and colonic tuberculosis. A) Contrast-enhanced CT demonstrates mural thickening and enhancement of the cecum and ascending colon with surrounding inflammatory changes (arrow). B and C) Multiple regional necrotic mesenteric lymph nodes are also evident (arrowhead).
      The radiologic differential for the appearance of colorectal TB includes amebic colitis, Crohn's disease, pseudomembranous and ischemic colitis, and malignancy.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.

      4. Hepatosplenic tuberculosis

      Hepatosplenic involvement is a rare manifestation of extrapulmonary TB and occurs more frequently as a result of hematogenous dissemination from a primary site of infection or by local spread from the GI tract.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Hickey A.J.
      • et al.
      A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.
      The two main forms of hepatosplenic TB are (i) the more common micronodular-miliary type and (ii) the rarer macronodular type.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.

      4.1 Liver

      Hepatic tuberculosis has been estimated to occur in 1% of active TB cases, with 79% due to micronodular-miliary TB and 21% due to macronodular-local hepatic TB.
      • Hickey A.J.
      • et al.
      A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.
      The tuberculous bacilli reach the liver via the hepatic artery in miliary TB, and via the portal vein in macronodular TB.
      • Chien R.N.
      • Lin P.Y.
      • Liaw Y.F.
      Hepatic tuberculosis: comparison of miliary and local form.
      It is described to occur more frequently in males with no specified age range.
      • Chaudhary P.
      Hepatobiliary tuberculosis.
      Hepatic tuberculosis commonly presents with non-specific symptoms such as hepatomegaly, fever, respiratory symptoms, abdominal pain, weight loss, and ascites leading to delayed diagnosis.
      • Hickey A.J.
      • et al.
      A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.
      ,
      • Tai W.-C.
      • et al.
      Liver tuberculosis in southern Taiwan: 15-years clinical experience.
      ,
      • Wang J.Y.
      • et al.
      Disseminated tuberculosis: a 10-year experience in a medical center.
      Jaundice may also be evident, indicating the extension of infection into the biliary system leading to the even more rare gallbladder tuberculosis. The gallbladder wall and mucosa are resistant to M. tuberculosis, and thus infection denotes a severe diffuse abdominal TB.
      • Xu X.F.
      • et al.
      Gallbladder tuberculosis: CT findings with histopathologic correlation.
      ,
      • Vanhoenacker F.M.
      • et al.
      Imaging of gastrointestinal and abdominal tuberculosis.
      Gallbladder involvement is extremely rare and is only seen in extensive and severe abdominal TB. Findings can include a large gallbladder with a thickened wall with a possible intraluminal soft tissue mass.
      • Vanhoenacker F.M.
      • et al.
      Imaging of gastrointestinal and abdominal tuberculosis.

      4.2 Spleen

      The spleen is an unusual organ to be affected by TB with several isolated literature cases being reported and is the cause of 4% of splenectomies in patients.
      • Simu G.
      • et al.
      Microscopic patterns in surgically removed spleens.
      However, it is the third most common organ to be affected in immunocompromised people with TB infection.
      • Gupta A.
      Splenic tuberculosis: a comprehensive review of literature.
      It is described to occur more frequently in males 19–53 years old.
      • Pottakkat B.
      • et al.
      Tuberculosis of the spleen as a cause of fever of unknown origin and splenomegaly.
      Splenic tuberculosis commonly presents with fever, hepatosplenomegaly, pallor, GI bleed, and weight loss.
      • Pottakkat B.
      • et al.
      Tuberculosis of the spleen as a cause of fever of unknown origin and splenomegaly.
      ,
      • Ho P.-L.
      • Chim C.-S.
      • Yuen K.-Y.
      Isolated splenic tuberculosis presenting with pyrexia of unknown origin.
      A micronodular or macronodular pattern can be seen in both hepatic and splenic tuberculosis. Ultrasound shows a diffusely hyperechoic liver or spleen.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      Micronodular or miliary TB appears as numerous tiny hypodense lesions on CT and is most commonly seen in patients with hematogenous spread of primary miliary pulmonary disease. These lesions may demonstrate minimal peripheral enhancement with IV contrast administration.
      • Kakkar C.
      • et al.
      Hepatic tuberculosis: a multimodality imaging review.
      These tiny lesions are often too small to be seen on CT, in which case the only apparent finding may be hepatosplenomegaly.
      • Pereira J.M.
      • et al.
      Abdominal tuberculosis: imaging features.
      In more advanced stages, the lesions undergo calcification which makes them easier to identify. The tiny nodules are sometimes better characterized by high-resolution ultrasound as hypoechoic lesions.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      Macronodular TB is less common and occurs secondary to the spread of tuberculous bacteria through the portal vein.
      • Gupta P.
      • et al.
      Common and uncommon imaging features of abdominal tuberculosis.
      These are seen on CT as single or multiple low attenuating lesions in a background of hepatosplenomegaly (Fig. 7, Fig. 8, Fig. 9). Post-contrast images can show early central enhancement, and calcifications can be seen in more chronic cases.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      The lesions also exhibit peripheral rim enhancement due to the presence of granulation tissue, thereby making the diagnosis and differentiation of TB from primary tumors and metastasis challenging. On MR imaging, the lesions are hypointense on T1-weighted imaging and isointense to hyperintense on T2-weighted imaging with a possible hypointense rim. Post-contrast studies usually show peripheral enhancement.
      • Kakkar C.
      • et al.
      Hepatic tuberculosis: a multimodality imaging review.
      Fig. 7
      Fig. 7Hepatic tuberculosis. A) US of liver shows multiple hypoechoic liver lesions. MRI of the same patient reveals B) multiple T2 fat sat hyperintense liver lesions with C) associated diffusion restriction and D) post-contrast enhancement.
      Fig. 8
      Fig. 8Splenic tuberculosis. A) US of spleen demonstrates a heterogenous hypoechoic structure (4.9 cm × 4.3 cm) without internal vascularity, suggestive of an abscess. B) T2-weighted image shows a hyperintense lobulated mass (arrow), suggestive of an abscess. Left pleural effusion is also identified. C) MRI 7 months post anti-TB treatment reveals near complete resolution of the splenic lesion with a small residual and scarring (arrow).
      Fig. 9
      Fig. 9Hepatosplenic tuberculosis in a young female with newly diagnosed HIV. A and B) Contrast-enhanced CT demonstrates hypo-enhancing nodules of variable size in the liver (arrows) and spleen (arrowheads). Periportal necrotic lymph nodes are also evident (asterisk). Bilateral pleural effusion and small volume ascites are present.
      The radiological differential for the appearance of hepatosplenic tuberculosis of the micronodular-miliary type includes lymphoma, metastasis, sarcoidosis and fungal infections (Candida, Aspergillus, Cryptococcus, histoplasmosis), while the differential for macronodular type tuberculosis includes pyogenic abscesses, metastasis, and primary malignancies. The additional differential for gallbladder involvement includes gallbladder carcinoma and adenomyomatosis.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Vanhoenacker F.M.
      • et al.
      Imaging of gastrointestinal and abdominal tuberculosis.
      ,
      • Ahmed S.
      • Horton K.M.
      • Fishman E.K.
      Splenic incidentalomas.

      5. Genitourinary tuberculosis

      The genitourinary (GU) tract is the second most common site for extrapulmonary tuberculosis after lymph node involvement, with a vast majority of cases (90%) occurring in developing countries.
      • Figueiredo A.A.
      • et al.
      Epidemiology of urogenital tuberculosis worldwide.
      Genitourinary TB occurs more commonly in older adults and predominantly affects males.
      • Figueiredo A.A.
      • et al.
      Epidemiology of urogenital tuberculosis worldwide.
      ,
      • Thwaites G.
      40 - tuberculosis.
      Genitourinary TB occurs more frequently in HIV-infected individuals compared to those without.
      • Nzerue C.
      • et al.
      Genitourinary tuberculosis in patients with HIV infection: clinical features in an inner-city hospital population.
      ,
      • Marques L.P.
      • et al.
      AIDS-associated renal tuberculosis.
      The onset and progression of genitourinary TB is usually insidious, with an approximate 20-year latency period between infection and expression of genitourinary TB.
      • Christensen W.I.
      Genitourinary tuberculosis: review of 102 cases.
      Patients with GU tuberculosis start with a pulmonary focus which through hematogenous seeding leads to infection of the kidneys, prostate and epididymis; bacilluria spreading the infection to the ureter, bladder, and prostate, with subsequent spread to the ejaculatory ducts, seminal vesicles, vas deferens and epididymis.
      • Figueiredo A.A.
      • Lucon A.M.
      • Srougi M.
      Urogenital tuberculosis.

      5.1 Kidney

      The kidneys are the most common site of GU tuberculous infection. Nearly 75% of renal TB cases have unilateral involvement.
      • Zissin R.
      • et al.
      Computerized tomography findings of abdominal tuberculosis: report of 19 cases.
      Presentation of renal TB is often non-specific – pyuria and microscopic hematuria may be found incidentally. In the early stages, edema and vasoconstriction in the renal parenchyma can lead to focal hypoperfusion on contrast-enhanced studies, giving an appearance similar to pyelonephritis.
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      Low attenuation parenchymal tumor-like lesions without urinary tract involvement can also occur rarely.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      The collecting system is most commonly involved in renal tuberculosis. Initially, only a few calyces are involved, with calyceal deformity or papillary necrosis. Eventual healing and fibrosis lead to multiple strictures resulting in uneven caliectasis, the most common feature seen on cross-sectional imaging (Fig. 10, Fig. 11). The caliectasis is not always seen on excretory urography due to poor opacification due to infundibular stenosis, giving the appearance of the “phantom calyx”.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      Urography can also show a “moth-eaten” calyx due to erosions leading to irregular collections of pools of contrast.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      In healed or chronic renal TB, atrophy, progressive hydronephrosis, and calcifications can occur. This leads to changes in morphology, with the kidneys appearing to have multiple cysts. Eventually, a “putty kidney” appearance occurs when dystrophic calcifications develop in the entire kidney.
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      Fig. 10
      Fig. 10Renal tuberculosis. A) Contrast-enhanced CT shows a hypo-enhancing cystic lesion in the left kidney (arrow). MRI demonstrates a well-defined, septate cystic lesion which is B) T1 hypointense and C) T2 hyperintense in the interpolar region. The lesion also has a thick T2 hypointense wall which shows D) post-contrast enhancement and E and F) diffusion restriction. G, H and I) MRI 3-months post anti-TB treatment shows a reduction in size of the lesion along with presence of caseating material within the lesion as apparent by increased diffusion restriction within the fluid content.
      Fig. 11
      Fig. 11Pelvicalyceal tuberculosis in a patient with known miliary tuberculosis. Contrast-enhanced CT demonstrates diffuse caliectasis with extensive thinning and calcification of the left renal parenchyma.
      The radiological differential for the appearance of renal tuberculosis includes papillary necrosis, medullary sponge kidney, transitional cell, and squamous cell carcinoma, chronic pyelonephritis, and xanthogranulomatous pyelonephritis.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Gibson M.S.
      • Puckett M.L.
      • Shelly M.E.
      Renal tuberculosis.

      5.2 Ureter

      Infection from the kidneys can spread down to involve the ureter. Ureteric tuberculosis is present in 50% of patients with genitourinary TB.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      The distal third of the ureter is the most common site of involvement in ureteric TB.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Zissin R.
      • et al.
      Computerized tomography findings of abdominal tuberculosis: report of 19 cases.
      In the early stages, intravenous urography may demonstrate dilatation and irregular appearance. CT imaging can show thickening of the ureteric wall and periureteric inflammatory changes. As the disease progresses, ulceration and chronic fibrotic changes lead to a corkscrew appearance of the ureters and proximal hydroureteronephrosis. Pipe-stem appearance of the ureter due to chronic thickening of the ureteric wall resulting and foreshortening can also occur.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      The most common locations for strictures are at the normal anatomic points of narrowing, namely the ureteropelvic junction, pelvic brim, and vesicoureteric junction.
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      The radiological differential for the appearance of ureteral tuberculosis includes ureteral stones and calcifications caused by schistosomiasis. Ureteral wall calcifications due to tuberculosis are infrequent but its presence in association with renal calcifications is more suggestive of tuberculous infection.
      • Prakash J.
      • et al.
      Extensive renal and ureteral calcification due to tuberculosis: rare images for an uncommon condition.

      5.3 Bladder

      Infection of the bladder with tuberculosis can occur either by way of hematogenous dissemination or through the passage of infected urine.
      • Thwaites G.
      40 - tuberculosis.
      With the progression of the infection to involve the bladder, urinary urgency, increased frequency, dysuria, hematuria and lumbar pain occur.
      • Christensen W.I.
      Genitourinary tuberculosis: review of 102 cases.
      ,
      • Figueiredo A.A.
      • Lucon A.M.
      • Srougi M.
      Urogenital tuberculosis.
      Imaging reveals a shrunken bladder with wall thickening that mimics transitional cell carcinoma.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      Filling defects due to bladder wall granulomas can also be seen. Advanced disease with chronic scarring eventually results in a thimble bladder, which is a small, contracted and irregular bladder. Calcifications in the bladder wall are rare.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      Complications include vesicoureteric reflux resulting from ureteric orifice fibrosis.
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      The radiological differential for the appearance of tuberculous bladder calcification includes iatrogenic causes such as cystitis post-radiation, chemotherapy (cyclophosphamide) and Bacillus Calmette-Guérin treatment (for bladder cancer); infectious causes such as schistosomiasis; and malignancy such as transitional cell carcinoma.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      ,
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.

      5.4 Genital TB

      5.4.1 Ovaries, fallopian tubes, and uterus

      Genital TB in women may mimic pelvic inflammatory disease and is accountable for nearly 10% of infertility cases in women globally, with a greater incidence in developing countries.
      • Figueiredo A.A.
      • et al.
      Epidemiology of urogenital tuberculosis worldwide.
      Isolated ovarian tuberculosis involvement is rare, usually affects those in endemic areas, and can mimic ovarian carcinoma.
      • Nebhani M.
      • et al.
      Tuberculose pelvienne simulant une tumeur ovarienne bilatérale: À propos d’un cas.
      ,
      • Rabesalama S.
      • et al.
      Isolated ovarian tuberculosis mimicking ovarian carcinoma: case report and literature review.
      Ovarian TB usually develops as a consequence of fallopian tuberculosis, with a resulting development of a tubo-ovarian abscess extending throughout the peritoneum.
      • Engin G.
      • et al.
      Imaging of extrapulmonary tuberculosis.
      Imaging has low specificity for differentiating between ovarian tuberculosis and malignancy due to similar appearances on ultrasound, CT, and MRI – heterogeneous masses with the potential to infiltrate the omentum and associated ascites and/or lymphadenopathy.
      • Nebhani M.
      • et al.
      Tuberculose pelvienne simulant une tumeur ovarienne bilatérale: À propos d’un cas.
      The fallopian tubes are involved in around 94% of those with genital tuberculosis, most commonly with bilateral involvement.
      • Wang L.-J.
      • et al.
      Pictorial essay. CT features of genitourinary tuberculosis.
      • Agarwal J.
      • Gupta J.K.
      Female genital tuberculosis—a retrospective clinico-pathologic study of 501 cases.
      • Abbara A.
      • Davidson R.N.
      • Medscape
      Etiology and management of genitourinary tuberculosis.
      If left untreated, the infection may spread to the peritoneum (causing peritonitis) and/or uterine cavity (causing endometritis).
      • Thwaites G.
      40 - tuberculosis.
      ,
      • Wang L.-J.
      • et al.
      Pictorial essay. CT features of genitourinary tuberculosis.
      Clinical symptoms include chronic lower abdominal pain, irregular vaginal bleeding, and infertility. Hysterosalpingogram shows features of tubal occlusion, most prominent in the isthmus and ampulla due to its rich blood supply.
      • Chavhan G.B.
      • et al.
      Female genital tuberculosis: hysterosalpingographic appearances.
      Multifocal constrictions and scarring of the fallopian tubes with hydro/pyosalpinx eventually result in a “beaded” or “rigid pipe stem” appearance (Fig. 12). The radiological differential for the appearance of fallopian tube tuberculosis includes salpingitis isthmica nodosa, which shows several diverticula filled with contrast on the hysterosalpingogram, and fallopian tube intraluminal endometriosis.
      • Revzin M.V.
      • et al.
      Imaging evaluation of fallopian tubes and related disease: a primer for radiologists.
      Fig. 12
      Fig. 12Tubo-ovarian tuberculosis in a patient with a history of pulmonary tuberculosis. A) US of right adnexa demonstrates a heterogenous hypoechoic lesion. Right ovary is not seen separately. B and C) Coronal T2 and post-contrast T1 sequences demonstrate bilateral hydrosalpinx (white arrows) and pyosalpinx (asterisks) with thick enhancing walls and surrounding fat stranding, suggestive of pelvic inflammatory disease. Bilateral vaginal cysts with thick enhancing walls are also noted (blue arrows). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
      Infection from fallopian tubes spreads to involve the endometrium in 50–70% of patients, although the myometrium is rarely affected.
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      ,
      • Mondal S.K.
      • Dutta T.K.
      A ten year clinicopathological study of female genital tuberculosis and impact on fertility.
      Severe endometrial adhesions in uterine tuberculosis may mimic Asherman syndrome. Vaginal and vulvar tuberculosis is extremely rare.

      5.4.2 Testis, epididymis, seminal vesicles and prostate

      Tuberculous involvement of male genital organs has been reported in 30%–90% of patients. Physical findings in male genital TB consist of a scrotal lump, epididymal hardening, or fistula.
      • Figueiredo A.A.
      • et al.
      Epidemiology of urogenital tuberculosis worldwide.
      The epididymis is the most commonly affected site (10–55%) in genital TB in males, owing to its rich blood supply.
      • Thwaites G.
      40 - tuberculosis.
      ,
      • Figueiredo A.A.
      • Lucon A.M.
      • Srougi M.
      Urogenital tuberculosis.
      The infection is generally unilateral and begins at the tail of the epididymis and thereby spreads to the entire duct.
      • Thwaites G.
      40 - tuberculosis.
      Pain, swelling and an enlarged epididymis and testis may be found on examination. In tuberculous epididymo-orchitis, the US shows swelling and heterogeneous echotexture of the involved segment (Fig. 13) or a heterogenous ill-defined hypoechoic testicular lesion; MRI shows a relatively low signal intensity of T2-weighted images, indicating inflammation or fibrosis (Fig. 14). The differential diagnosis of tuberculous epididymo-orchitis includes bacteria epididymitis (due to N. gonorrhea, and C. trachomatis).
      Fig. 13
      Fig. 13Tuberculous epididymo-orchitis in a patient with miliary tuberculosis. US of the testes demonstrates heterogenous collection with peripheral vascularity in the lower testicle and epididymal tail region.
      Fig. 14
      Fig. 14Tuberculous epididymo-orchitis in a patient with known pulmonary tuberculosis. A and B) US of the right testicle shows an ill-defined hypoechoic lesion and an enlarged epididymis with some peripheral vascularity. MRI demonstrates an ill-defined C) T2 hypointense lesion and D) T1 intermediate signal lesion with E and F) multiloculated peripheral enhancement involving the epididymal head and thick enhancing spermatic cord on the right side.
      Tuberculosis of the seminal vesicles appears as wall thickening, contraction, and intraluminal or wall calcifications.
      • Jung Y.Y.
      • Kim J.K.
      • Cho K.S.
      Genitourinary tuberculosis: comprehensive cross-sectional imaging.
      Tuberculosis of the prostate is rare and may manifest as either prostatitis or an abscess.
      • Wang L.-J.
      • et al.
      Pictorial essay. CT features of genitourinary tuberculosis.
      Nodularity or enlargement may be appreciated on rectal examination. Tuberculosis of the seminal vesicles or prostate may result in necrosis, calcification, caseation, and cavitation.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      The US of tuberculous prostatitis reveals hypoechogenicity and increased vascularity, similar to that seen in prostate cancer. Prostate tuberculosis appears as a diffuse, radiating area with streaky low signal intensity on T2-weighted MRI as referred to as the “watermelon skin” sign.
      • Engin G.
      • et al.
      Imaging of extrapulmonary tuberculosis.
      ,
      • Cheng Y.
      • et al.
      Multiparametric magnetic resonance imaging characteristics of prostate tuberculosis.
      ,
      • Wang J.H.
      • Sheu M.H.
      • Lee R.C.
      Tuberculosis of the prostate: MR appearance.
      It can also appear as an enlarged heterogeneous prostate with small abscesses in advanced stages. Diffuse dystrophic calcifications may be seen with long-standing prostatic tuberculosis. The radiological differential for the appearance of prostatic tuberculosis is prostate carcinoma, which is usually seen as an area of low signal intensity within the normal high signal intensity of the peripheral zone of the prostate, with enhancement on post-contrast images.
      • Lovegrove C.E.
      • et al.
      Prostate imaging features that indicate benign or malignant pathology on biopsy.
      Urethral tuberculosis is very rare but may occur with prostate involvement, and results in urethral strictures or fistulas.
      • Indudhara R.
      • Vaidyanathan S.
      • Radotra B.D.
      Urethral tuberculosis.
      Urethroperineal fistulas, which result in a “watering can perineum”, can also be seen with schistosomiasis infections.
      • Kawashima A.
      • et al.
      Imaging of urethral disease: a pictorial review.
      Penile tuberculosis is also rare and can manifest as an ulcerative lesion or cause penis deformity.
      • Singal A.
      • et al.
      Tuberculosis of the glans penis: an important differential diagnosis of genital ulcer disease.
      ,
      • Vasanthi R.
      • Ramesh V.
      Tuberculous infection of the male genitalia.

      6. Tuberculous peritonitis

      Peritoneal spread of tuberculosis the second most common presentation of abdominal TB, affecting between 31 and 58% of cases.
      • Hanson R.D.
      • Hunter T.B.
      Tuberculous peritonitis: CT appearance.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      • Sheldon C.D.
      • et al.
      Incidence of abdominal tuberculosis in Bangladeshi migrants in East London.
      It mainly occurs secondary to hematogenous spread from a pulmonary focus, but may also occur from lesions in adjacent organs or rupture of an infected lymph node or fallopian tubes.
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      ,
      • Singh M.M.
      • Bhargava A.N.
      • Jain K.P.
      Tuberculous peritonitis. An evaluation of pathogenetic mechanisms, diagnostic procedures and therapeutic measures.
      It equally affects both sexes and is mostly seen in the age ranges of 35–45 years old.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      Three forms of tuberculous peritonitis have been described
      • Burrill J.
      • et al.
      Tuberculosis: a radiologic review.
      ,
      • Leder R.A.
      • Low V.H.
      Tuberculosis of the abdomen.
      ,
      • Ha H.K.
      • et al.
      CT differentiation of tuberculous peritonitis and peritoneal carcinomatosis.
      : wet, fibrotic, and dry. The three forms have overlapping clinical manifestations of abdominal pain and tenderness, ascites, and fever, except for the dry-plastic type which does not present with abdominal distention. The wet type is the most common, occurring in 90% of cases, and is characterized by a significant amount of free or loculated ascites which is usually hyperdense (20–45 HU) due to high protein content (Fig. 15). The fibrotic fixed type occurs in 60% of cases and is characterized by omental thickening and enhancement, omental “cake-like” mass, fixed and matted bowel loops and mesentery, sometimes with loculated ascites and may progress to an abdominal cocoon or encapsulating peritoneal sclerosis with intestinal obstruction (Fig. 16). Dry or plastic-type is the least common type, occurring in 10% of cases and is characterized by fibrous adhesions of bowel loops, mesenteric thickening, and caseous mesenteric lymphadenopathy. Radiological features of different types can be seen in the same patient, with varying degrees of mesenteric and omental involvement.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      ,
      • Srivastava U.
      • et al.
      Tuberculous peritonitis.
      Fig. 15
      Fig. 15Tuberculous peritonitis. Contrast-enhanced CT demonstrates ascites with omental thickening and caking (arrow) along with peritoneal thickening and enhancement (arrowhead).
      Fig. 16
      Fig. 16Tuberculous peritonitis. A and B) Contrast-enhanced CT demonstrates diffuse thickening of proximal bowel with matted loops and loculated ascites. C and D) Contrast-enhanced CT 6 months post anti-TB treatment shows a thick enhancing sac-like structure with matted bowel loops in the center of the abdomen and proximal bowel dilation, indicating encapsulating peritoneal sclerosis (abdominal cocoon).
      The radiological differential for the appearance of tuberculous peritonitis includes non-tuberculous peritonitis, disseminated peritoneal carcinomatosis, ovarian carcinoma, and peritoneal mesothelioma.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      ,
      • Ha H.K.
      • et al.
      CT differentiation of tuberculous peritonitis and peritoneal carcinomatosis.
      ,
      • Bilgin T.
      • et al.
      Peritoneal tuberculosis with pelvic abdominal mass, ascites and elevated CA 125 mimicking advanced ovarian carcinoma: a series of 10 cases.
      ,
      • Rodríguez E.
      • Pombo F.
      Peritoneal tuberculosis versus peritoneal carcinomatosis: distinction based on CT findings.

      7. Tuberculous abscess

      A tuberculous abscess is a rare manifestation of tuberculosis, usually presenting as a complication of primary tuberculous infection but can also uncommonly present as an isolated form of primary tuberculosis.
      • Alawad A.A.M.
      • Gismalla M.D.
      Tuberculous abscess of the anterior abdominal wall: an unusual site of presentation.
      • Malhotra M.K.
      Cold abscess of the anterior abdominal wall: an unusual primary presentation.
      • Thakur S.K.S.
      • Sapatnekar V.
      • Pariyani R.
      Unusual presentation of abdominal Koch - cold abscess.
      Abdominal tubercular abscesses can involve the paraspinal or psoas muscles, the anterior abdominal wall, or be intra-peritoneal. Paraspinal or psoas muscle abscesses are often related to TB infection involving the vertebral bodies (Pott's disease) with subsequent extension to the adjacent muscle. The infection is usually restricted to one muscle, and clinical manifestation includes constitutional symptoms in addition to progressive pain and swelling of the affected site, and limitation of hip joint movement if the psoas muscle is affected.
      • Alawad A.A.M.
      • Gismalla M.D.
      Tuberculous abscess of the anterior abdominal wall: an unusual site of presentation.
      ,
      • Thakur S.K.S.
      • Sapatnekar V.
      • Pariyani R.
      Unusual presentation of abdominal Koch - cold abscess.
      An isolated paraspinal cold abscess can also be seen, with more chronic cases showing calcific foci.
      • Harisinghani M.G.
      • et al.
      Tuberculosis from head to toe.
      Intraperitoneal abscesses are often multiloculated, peripherally enhancing and may have foci of calcifications (Fig. 17, Fig. 18). A high index of suspicion for tuberculous abscess should be present when other changes such as peripherally enhancing lymphadenopathy, and peritoneal, mesenteric, and omental changes are seen.
      • Dong P.
      • et al.
      Intraperitoneal tuberculous abscess: computed tomography features.
      Fig. 17
      Fig. 17Tuberculous abscess. Contrast-enhanced CT demonstrates a peripherally enhancing collection in the enlarged right psoas muscle (arrow) which appears connected (asterisk) to adjacent multiple necrotic lymph nodes (arrowhead).
      Fig. 18
      Fig. 18Tuberculous abscess in multiple different patients. Contrast-enhanced CT demonstrates a peripherally enhancing A) mesenteric, B) left diaphragmatic crus, C) pericolic abscess (asterisk). A small left gluteal abscess is also seen (arrow).
      The radiological differential for the appearance of abdominal tuberculous abscess includes other bacterial and fungal infections, tuberculoma, necrotizing fasciitis, hematoma, and soft-tissue tumors.
      • Alawad A.A.M.
      • Gismalla M.D.
      Tuberculous abscess of the anterior abdominal wall: an unusual site of presentation.
      ,
      • Pacheco C.
      • et al.
      Cutaneous tuberculosis as metastatic tuberculous abscess.
      ,
      • Sezgin B.
      • et al.
      Concomitant cutaneous metastatic tuberculous abscesses and multifocal skeletal tuberculosis.

      8. Management and treatment

      The approach to establishing the diagnosis of abdominal TB requires a high index of suspicion as often the clinical and radiologic findings are non-specific. Abdominal TB should be suspected in those patients with clinical manifestations (such as fever, weight loss, diarrhea, abdominal pain, distension and/or mass, hepatomegaly, hematuria) along with relevant epidemiological factors (such as past or present residence in/travel to an endemic country, history of prior TB infection or possible exposure). Laboratory findings may reveal normocytic anemic, thrombocytosis and/or an elevated erythrocyte sedimentation rate and C-reactive protein.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      ,
      • Rai S.
      • Thomas W.M.
      Diagnosis of abdominal tuberculosis: the importance of laparoscopy.
      ,
      • Kapoor V.K.
      Abdominal tuberculosis.
      The definitive diagnosis of abdominal TB may be established through bacteriologic examination of clinical specimens (e.g., ascitic fluid, urine, pus or biopsy specimens) via acid-fact bacilli (AFB) smear, culture, and nucleic acid amplification test (NAAT).
      • Centers for Disease Control and Prevention
      Chapter 4: diagnosis of tuberculosis disease.
      AFB smear and culture sensitivities are low (<50%). Nevertheless, culture is particularly useful to conduct drug-susceptibility testing and genotyping. Culture results can take up to 12 weeks (depending on the broth culture system used) compared to the rapid identification in hours through NAAT which has high sensitivity (95% in smear-positive cases) and specificity (98%) for detecting extrapulmonary TB.
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      ,
      • Maynard-Smith L.
      • et al.
      Diagnostic accuracy of the Xpert MTB/RIF assay for extrapulmonary and pulmonary tuberculosis when testing non-respiratory samples: a systematic review.
      ,
      • Diaz M.L.
      • et al.
      Polymerase chain reaction for the detection of Mycobacterium tuberculosis DNA in tissue and assessment of its utility in the diagnosis of hepatic granulomas.
      Workup for abdominal TB should also include radiologic imaging; CT would be preferred for evaluation as it allows for the assessment of lymphadenopathy, ascites, and peritoneal and solid organ involvement.
      • Suri S.
      • Gupta S.
      • Suri R.
      Computed tomography in abdominal tuberculosis.
      Other imaging modalities can also be helpful – ultrasound is useful for identifying lymphadenopathy, ascites and peritoneal and intestinal thickening, and barium enema can demonstrate mucosal ulcerations, strictures and ileocecal valve incompetence.
      • Debi U.
      • et al.
      Abdominal tuberculosis of the gastrointestinal tract: revisited.
      An abdominal X-ray can be useful for identifying air-fluid levels (during the presentation of intestinal obstruction), and calcifications present in the liver and/or ureter.
      • Hickey A.J.
      • et al.
      A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.
      In the presence of ascites, patients should undergo diagnostic paracentesis with the fluid analyzed for adenosine deaminase (ADA) level and in addition to acid-fast bacillus (AFB) smear, culture, nucleic acid amplification test (NAAT), and routine tests (cell count with differential, albumin and protein levels, Gram stain). Patients with peritoneal TB have a lymphocytic predominance with a low serum-ascites albumin gap (SAAG, <1.1 g/dL).
      • Sanai F.M.
      • Bzeizi K.I.
      Systematic review: tuberculous peritonitis--presenting features, diagnostic strategies and treatment.
      An elevated ascites ADA level (30 to 39 international units/L) in non-cirrhotic patients helps support the diagnosis of peritoneal TB
      • Rathi P.
      • Gambhire P.
      Abdominal Tuberculosis.
      ,
      • Lewinsohn D.M.
      • et al.
      Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children.
      but does not establish it with certainty. In the case of non-diagnostic ascitic fluid or absence of ascites, tissue biopsy should be pursued as guided by the extent of anatomic involvement seen on imaging.
      • Rathi P.
      • Gambhire P.
      Abdominal Tuberculosis.
      Histology may demonstrate caseating granulomas with necrosis, which is not pathognomonic by itself but helps support the diagnosis of TB in the setting of other clinical, epidemiologic and imaging findings.
      • Hickey A.J.
      • et al.
      A systematic review of hepatic tuberculosis with considerations in human immunodeficiency virus co-infection.
      The tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) may be positive in patients with abdominal TB, however, they do not differentiate between active and latent TB infection.
      • Kapoor V.K.
      Abdominal tuberculosis.
      While not having enough sensitivity (74%), IGRA tests have good specificity (87%) which can help differentiate intestinal TB from Chron's disease.
      • Chen W.
      • et al.
      Effectiveness of interferon-gamma release assays for differentiating intestinal tuberculosis from Crohn’s disease: a meta-analysis.
      Data on stool polymerase chain reaction (PCR) utility is limited, but small studies have reported good sensitivity (79–100%) and specificity (88–100%) in smear-positive cases, and so this may be used as an adjunct for the diagnosis of intestinal TB.
      • Kokuto H.
      • et al.
      Detection of Mycobacterium tuberculosis (MTB) in fecal specimens from adults diagnosed with pulmonary tuberculosis using the Xpert MTB/rifampicin test.
      ,
      • Ramadass B.
      • et al.
      Fecal polymerase chain reaction for Mycobacterium tuberculosis IS6110 to distinguish Crohn’s disease from intestinal tuberculosis.
      The mainstay of treatment for abdominal TB is with anti-tuberculous therapy. The current INDEX-TB guidelines recommend standard treatment for all forms of abdominal TB which consists of a two-month regimen of four drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) followed by a four-month regimen of two drug (rifampicin and isoniazid).
      • Sharma S.K.
      • et al.
      Index-TB guidelines: guidelines on extrapulmonary tuberculosis for India.
      • Jullien S.
      • et al.
      Six-month therapy for abdominal tuberculosis.
      • Makharia G.K.
      • et al.
      Intermittent directly observed therapy for abdominal tuberculosis: a multicenter randomized controlled trial comparing 6 months versus 9 months of therapy.
      Surgery may be warranted in cases of complications such as abscess and/or fistula formation, bleeding, bowel perforation and/or obstruction and stricture formation, and in the absence of response to anti-tuberculous treatment within two weeks to evaluate for alternative diagnoses such as Chron's disease and lymphoma.
      • Kapoor V.K.
      Abdominal tuberculosis.
      Delay in the initiation of anti-tuberculous therapy is associated with worse prognosis and higher mortality,
      • Wang J.Y.
      • et al.
      Disseminated tuberculosis: a 10-year experience in a medical center.
      ,
      • Chow K.M.
      • et al.
      Tuberculous peritonitis-associated mortality is high among patients waiting for the results of mycobacterial cultures of ascitic fluid samples.
      which further emphasizes the need for timely evaluation and initiation of therapy.

      9. Conclusion

      Tuberculosis is a major source of public health concern worldwide affecting virtually every organ system. A high index of clinical suspicion and knowledge about the appearance of TB infection within various organ systems, and its mimics, is central to guiding appropriate timely treatment, especially in high-risk populations.

      Declaration of competing interest

      H. L., S. A., F. S. A., S. L and S. F.: nothing to disclose.

      Acknowledgments

      Open Access funding provided by the Qatar National Library .

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