Histoplasma capsulatum is an important pathogen that is the most commonly diagnosed endemic mycosis in the gastrointestinal tract of immunocompromised hosts. Failure to recognize and treat disseminated histoplasmosis in AIDS patients invariably leads to death. Gastrointestinal manifestations frequently involve the terminal ileum and cecum, and depending on the layer of bowel wall involved present as bleeding, obstruction, perforation, or peritonitis. Because they can be variable in appearance, they may be mistaken for Crohn’s disease or malignant tumors. Four distinct pathologic patterns of GI histoplasmosis have been described that all have differing clinical presentations. We report a case of a non-AIDS patient who presented with a near-obstructing colonic mass suspicious for advanced malignancy but was found to have histoplasmosis on final pathology. The patient underwent successful operative resection, systemic anti-fungal therapy, and extensive workup for immunosuppressive disorders, which were negative. The patient was from an area in Mexico known to be endemic for histoplasmosis. This is the first report of a colonic mass lesion occurring in a non-AIDS patient, and review of the worldwide literature regarding GI histoplasmosis reveals excellent long-term survival with aggressive therapy. We discuss the surgical and medical management of colonic histoplasmosis in this report.
HISTOPLASMA CAPSULATUM is the most commonly diagnosed endemic mycosis in the gastrointestinal tract of immunocompromised hosts, specifically AIDS patients.1 In the immunocompetent patient, inhalation of spores leads to a self-limited respiratory infection, but in the immunocompromised patient, disseminated histoplasmosis can occur. Gastrointestinal involvement occurs in 50-70 per cent of cases of disseminated histoplasmosis due to hematogenous seeding of the GI tract and manifests as a wide variety of clinical presentations.2 The terminal ileum and cecum are typically involved, and patients present with nonspecific findings such as bleeding, obstruction, or chronic pain. In this report, we discuss a case of a nonimmunocompromised patient who presented with a nearobstructing colonic mass suspicious for malignancy but demonstrated histoplasmosis on final pathology.
Case Report
A 52-year-old female with end-stage renal disease due to hypertension and type II diabetes complained of 3 months of constipation, vague abdominal pain, mild weight loss, and fatigue. Physical examination revealed a thin female with normal vital signs and normal abdominal findings. Rectal exam did not reveal any masses, but she was found to have guaiac-positive stools. Laboratory results were white blood cell count 5900/cc, hemoglobin 11.3 g/dL, hematocrit 33.5 per cent, platelet count 399,000/cc, alkaline phosphatase 84 TU/L, serum albumin 2.7 g/dL, and CEA 0.8 g/L. Upper endoscopy showed mild gastritis, and colonoscopy showed a near- obstructing, fungating mass in the midtransverse colon as well as an irregular mass in the cecum, both suspicious for malignancy (Fig. 1). Biopsies were done, and the transverse colon mass demonstrated tubular adenoma, and the cecal mass biopsy showed tubular adenoma with severe dysplasia. The cecum and distal transverse colon appeared thickened on a CT scan of the abdomen and pelvis (Fig. 2), but there was no evidence of metastatic disease or lymphadenopathy. Surgical intervention was discussed with the patient and her family in order to relieve the obstruction as well as for definitive treatment of a presumed malignancy.
FIG. 1. Endoscopic view of transverse colon muss suspicious for malignancy. Biopsy showed tubular adenoma. Final surgical pathology demonstrated histoplasmosis.
After bowel preparation, the patient underwent exploratory laparotomy and subtotal colectomy with ileosigmoid anastomosis. Intraoperative findings included the cccal and transverse colon mass suspicious for malignancy as well as peritoneal studding throughout the mesentery and small bowel consistent with carcinomatosis. The patient recovered in the postoperative period without incident. Histopathologic analysis revealed a Tl adcnocarcinoma of the eeeal mass with O out of 20 lymph nodes positive for malignancy, making the stage TlNOMx. The transverse colon mass interestingly did not demonstrate carcinoma, and instead histoplasmosis was identified in the thickened, narrowed colon.
FIG. 2. Conipiiled tomography scan of abdomen and pelvis showing thick-walled cecum that on final pathology was a T1 adenocarcinoma with evidence of histoplasmosis throughout colonie specimen.
Infectious disease consultation was obtained, and the patient was noted Io be from an area of Mexico endemic for histoplasmosis. Her urine Hisloplamna antigen was positive at 1.38 units, and her serum Hisloplcisma antibody was 0.57 units. Chest X-ray and chest CT did not show pulmonary manifestations of histoplasmosis. She was treated with amphotericin B initially and then switched to oral itraconazole as an outpatient. Serum HIV test was negative on three separate occasions, and she has been doing well 1 year postoperatively without any evidence of recurrence.
Pathology
The specimen consisted of a 75-cm length of right, transverse, and left colon that was 13 cm in maximum diameter. On cut section there was a tan-brown hemorrhagic, soft mass measuring 9 8 4 cm in the cecum, with 4 cm of proximal free margin of terminal ileum. The serosal surface near this mass appeared thickened. Multiple small nodules, ranging from 0.2 to 0.5 cm, as well as extensive ulceration were noted within the mucosa. The transverse colon stricture measured three by 6 cm and was located near the splenic flexure (Fig. 3). It showed marked diffuse thickening of the colonie wall and was noted to be nearly obstructing with focal ulcerations.
Final pathology of the cecal mass showed adenocarcinoma arising from a villous adenoma with superficial invasion of the submucosa. No tumor was identified in 20 lymph nodes. No carcinoma noted in the peritoneal biopsies, making the pathologic stage of the cecal cancer TlNOMx . Most of the lymph nodes did contain caseous necrosis and granuloma formation with histoplasmosis present (Fig. 4). Histoplasmosis was found scattered throughout the terminal ileum, cecum, and rest of the colon (Figs. 5 and 6). Small pseudopolyps found in the ascending colon mucosa demonstrated lymphoid aggregates that contained histoplasmosis-containing histiocytes. The transverse colon stricture was found to have histiocytic nodules in the mucosa and caseating granulomata involving the muscularis propria, subserosa, and multiple lymph nodes. The terminal ileum and appendix were also involved with hisloplasmosis, but the proximal margin of the specimen was free of infection.
FIG. 3. Gross picture of transverse colon specimen showing stricture and wall thickening with dilated proximal segment and collapsed distal bowel.
FIG. 4. Transverse eolon stricture due Io hisloplasmosis. Low- power view showing caseating granuloma in the muscularis propria as well as transmural inflammation with pericolitis (H&E stain, magnification 31).
FIG. 5. High-power view of strictured colon segment demonstrating intracellular Histoplasma. The organisms are loeated within histiocytes (black arrow) and multinuclcated giant cells (clear arrow). Note the characteristic halo surrounding the organism (H&E stain, magnification 1560).
Discussion
Histoplasma capsulatum is a ubiquitous soil-dwelling saprophyte that is found worldwide, but in the United States is endemic to the Ohio, Missouri, and Mississippi River Valleys. The respiratory tract is the primary site of infection. When the disease becomes disseminated, there is hematogenous seeding into the GI tract that is highly morbid if left untreated.1 More than 70 per cent of AIDS patients will have presence of GI histoplasmosis in the colon found on autopsy, but clinical symptoms will typically develop in only 10- 45 per cent of patients.2 Disseminated histoplasmosis is exceedingly rare in the immunocompetent patient, and presentation in this setting requires an extensive workup for an immunocompromised state.
FIG. 6. Electron microscopy of Histoplasma organism showing nucleus, mitochondria, and capsule (magnification 20,000).
The diagnosis is most accurately established by tissue culture or histological identification of the biopsy specimen. Urine assay for the antigen can be performed rapidly, which is highly sensitive in establishing the diagnosis and assessing the therapeutic response in patients with disseminated histoplasmosis. Serum antibody titers are less sensitive, and serologies may not even be positive in the AIDS patient. Isolating the organism in blood or bone marrow is time- consuming and sometimes takes up to 8 weeks for identification.
The mainstay of therapy for disseminated histoplasmosis with GI involvement is systemic antifungal therapy. Amphotericin is given with a recommended cumulative dose of I to 2 g followed by long- term suppressive therapy with oral itraconazole. The risk of relapse is significantly reduced by maintenance therapy.3 The disease is highly treatable, a\nd most patients remain symptom-free after therapy for 12 to 24 months, emphasizing the importance of accurate diagnosis and prompt treatment.
Pour distinct patterns of GI histoplasmosis have been described each with differing clinical presentations.”4 First, subclinical infection without gross abnormality but the presence of fungi in the lamina propria can be found on biopsy. The second variety involves the presence of small pseudopolyps and plaques that is due to aggregates of parasitized macrophages. A third group is characterized by discrete ulcerations in the mucosa. Last, there can be focal thickening of the bowel, similar to the patient in this report, that mimics a colonie mass suspicious for malignancy or Crohn’s disease and can lead to obstructive symptoms
The presentation of GI histoplasmosis as a colonie mass or stricture is rare, and review of the literature reveals less than 20 patients who have this clinical picture (Table I). The diagnosis of histoplasmosis for such patients is usually is made after surgical resection, and it has been suggested that this subset of patients is unlikely to resolve with antibiotics alone.5 In a review of 52 patients at one hospital with disseminated GI histoplasmosis, three (6%) presented with an obstructing colon mass and required surgical resection.6 Out of 77 patients in a review of the literature of disseminated histoplasmosis, six (8%) presented as an obstructive mass or stricture in the colon.2 In some of these patients, the obstructing mass was their first presentation of AIDS, and they initially underwent attempted curative surgical resection with the presumed diagnosis of malignancy. All of the previous patients described in the literature had a documented immunocompromiscd state.
Our patient is interesting in that she is the first ease report of colonie histoplasmosis presenting as a mass or stricture without a documented immunodeficiency, such as AIDS, Job’s syndrome, chronic steroid use, or chemotherapy (Table 1). Although this patient did have renal failure requiring dialysis, such patients are typically not prone to develop opportunistic infections unless they are transplant recipients or have concomitant HlV infection.7 This patient also had a Tl adenocarcinoma of the cecum, and the previously described cases in the literature did not reveal any other synchronous malignancies. Like many of the previous cases, the diagnosis of histoplasmosis was only made after surgical resection.
In summary, the varied presentations of GI histoplasmosis in the immunocompromised patient require prompt and aggressive treatment. Any HIV-positive patient with nonspecific abdominal complaints is at risk for opportunistic infections of the colon, and histoplasmosis should be in the differential. Also, the diagnosis should be considered in patients not known to be immunocompromised but from an endemic area of histoplasmosis. Colonoscopy and biopsy should be obtained that confirm the diagnosis. Urine assay for Histoplasma antigen and serum antibody liters also aid in the diagnosis. Although antibiotics are effective, failure to improve or inability to rule out malignancy mandates surgical resection as if the lesion is a cancer. Long-term maintenance therapy with antifungal medication should be instituted to prevent relapse.
TABLE 1. Reported cases of Colonie Histoplasmosis Presenting as a Mass-Like Lesion
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JASON T. LEE, M.D.,* MATTHEW R. DIXON, M.D.,* ZURI MURRELL, M.D.,* VIKEN KONYALIAN, M.D.,* RODOLFO AGBUNAG, M.D.,* SASSAN ROSTAMI, M.D.,[dagger] SAMUEL FRENCH, M.D.,[dagger] RAVIN R. KUMAR, M.D.*
From the * Department of Surgery and [dagger] Department of Pathology, Harbor-UCLA Medical Center, Torrance, California
Presented at the Annual Meeting, Southern California Chapter of the American College of Surgeons, January 16-18, 2004, Santa Barbara, California.
Address correspondence and reprint requests to Ravin R. Kumar, M.D., Chief, Division of Colorectal Surgery, Harbor-UCLA Medical Center, 1000 West Carson Street, Box 25, Torrance, CA 90509.
Copyright The Southeastern Surgical Congress Nov 2004
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