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26 August 2015 - Case of the Week #362

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Case of the Week #362

Clinical History:
A 30 year old man had emergency surgery for acute abdominal pain, with suspected ileal perforation. The terminal ileum, cecum, ascending colon and appendix were excised.

Gross description:
Figure 1: 12 cm specimen consisting of terminal ileum (8.0 cm) with two sites of perforation (1.8 x 1.5 cm and 1.0 x 1.0 cm), cecum, ascending colon (4.0 cm) and appendix (6.0 x 1.0 cm).

Figure 2: Cut section with ulcerated areas, with serosal exudate and a 0.5 cm lymph node in the serosa.

Gross images:

Micro images:

What is your diagnosis?

Perforated ileum with typhoid granuloma in serosal lymph node


Micro description:
Figure 3: Ileal mucosa adjacent to the ulcerated site with edematous submucosa and mucosal inflammation.

Figures 4, 5, 6: Ulceration with characteristic chronic inflammatory cells of typhoid with lymphocytes, histiocytes and plasma cells.

Figures 7, 8, 9: Serosal lymph node with typhoid granuloma: macrophages (typhoid cells), giant cells, lymphocytes.

Figure 10: Serosal acute inflammation with exudate.

Typhoid ileal perforation is the most common surgical complication of typhoid fever, and remains a problem in developing countries. It occurs as a single perforation in 86% of cases, but can present as multiple perforations in a small percentage. The terminal ileum is the most common site of perforation (Clin Infect Dis 2004;39:61).

Typhoid fever is caused by the bacterium Salmonella typhi, a gram negative bacillus which infects only humans. Transmission is fecal-oral, and often due to contaminated drinking water. The ingested bacteria multiply in the intestine and pass through Peyer's patches. The organisms are taken up by the reticuloendothelial system and ultimately pass through the liver, are excreted in bile, and return to the intestines where they continue to proliferate in the previously sensitized Peyer's patches. This leads to a hypersensitivity reaction causing hypertrophy of the lymphoid tissue, congestion of the mucosa, blockage of capillaries, necrosis, ulceration and possibly perforation (Principles and Practice of Surgery including Pathology in the Tropics (2009), Rubin's Pathology: Clinicopathologic Foundations of Medicine (2014)).

Characteristic histopathologic features include a mucosal ulcer bed overlying a discrete, dense aggregate of inflammatory cells consisting of lymphocytes, histiocytes and plasma cells; neutrophils are usually inconspicuous outside of the ulcer (J Chir (Paris) 1994;131:90). The adjacent villi are blunted, indicative of chronic injury (Clin Infect Dis 2004;39:61). Admixed are large macrophages, termed "typhoid cells", which phagocytose the typhoid bacteria as well as erythrocytes and degenerated lymphocytes (J Chir (Paris) 1994;131:90). Mesenteric lymph nodes contain typhoid granulomas composed of aggregates of these cells. Typhoid granulomas can also be seen in the liver, spleen and bone marrow (J Natl Med Assoc 2007;99:1042).

The differential diagnosis includes tuberculosis, pseudotuberculosis (see Yersinia of small bowel, Yersinia pseudotuberculosis of lymph nodes, Yersinia granulomatous appendicitis of appendix), sarcoidosis and histoplasmosis.

The morbidity and mortality is significant, with mortality rates from 15-20% (Intern Med 2004;43:436, Med Princ Pract 2009;18:239); however, with early appropriate antimicrobial therapy, most cases resolve without complications (Clin Infect Dis 2004;39:61). Morbidity is due to wound infection, burst abdomen and fistula formation. Factors affecting mortality include the number of perforations, time to treatment and peritoneal contamination (Intern Med 2004;43:436, Med Princ Pract 2009;18:239). The fatality rate is highest in patients age 30 or older or less than 1 year old (Clin Infect Dis 2004;39:61).

Discussion by Jennifer R. Kaley, M.D., University of Arkansas for Medical Sciences