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Year : 2015  |  Volume : 8  |  Issue : 6  |  Page : 775-778  

Autopsy report of disseminated histoplasmosis: An important differential of adrenal enlargement

Department of Pathology, Lokmanya Tilak Municipal Medical College, Mumbai, Maharashtra, India

Date of Web Publication19-Nov-2015

Correspondence Address:
Sonali Saraf
C-404, Siddhivinayak Annexe, Sitaram Jadhav Road, Lower Parel West, Mumbai - 400 013, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-2870.169927

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A 57-year-old diabetic male, presented with altered sensorium since 2 days. He had a history of weight loss, loss of appetite, intermittent low-grade fever of 6 months duration. He had been administered empirical antituberculous therapy some months ago with no alleviation of symptoms. On examination, he was asthenic, normotensive, and anemic with hepatosplenomegaly. Ultra-sonography abdomen revealed bilateral enlarged adrenals with hepatosplenomegaly. Clinically impression was of tuberculosis disseminated malignancy. He expired within 2 days of admission. At autopsy, both the adrenals were markedly enlarged showing extensive areas of necrosis on the cut surface. Histology showed them to be brimming with colonies of yeast-forms of Histoplasma capsulatum. These organisms were also seen in the spleen, lungs and kidneys. The patient had died of septicemia following disseminated histoplasmosis that was, unfortunately, not diagnosed during his life. Histoplasmosis is amenable to treatment with Amphotericin B. Prompt diagnosis and treatment could have helped in salvaging this patient.

Keywords: Adrenals, diabetes, Histoplasma capsulatum

How to cite this article:
Kalgutkar AD, Saraf S, Pagare S, Patil MV. Autopsy report of disseminated histoplasmosis: An important differential of adrenal enlargement. Med J DY Patil Univ 2015;8:775-8

How to cite this URL:
Kalgutkar AD, Saraf S, Pagare S, Patil MV. Autopsy report of disseminated histoplasmosis: An important differential of adrenal enlargement. Med J DY Patil Univ [serial online] 2015 [cited 2020 Dec 1];8:775-8. Available from:

  Introduction Top

Histoplasma capsulatum, a thermal dimorphic fungus, is the etiologic agent of histoplasmosis. It is most prevalent endemic mycosis in North America, whereas in India it is seen in the Gangetic delta. The clinical manifestations of the disease can vary from asymptomatic disease in immunocompetent individuals to disseminated disease in infants, immunosuppressed patients like AIDS, diabetes mellitus [1] or in the elderly. [2] The involvement of the adrenal glands is not uncommon in the disseminated form of the disease. Patients may present asymptomatic adrenal nodules or infrequently, with an addisonian crisis. The final diagnosis frequently requires tissue analysis.

This autopsy case is of an elderly sero-negative diabetic man hailing from a nonendemic region who had involvement of adrenals by colonies of histoplasma along with dissemination to the spleen, kidneys and lungs.

  Case Report Top

We report a case of disseminated histoplasmosis in a 57 year old nonimmunocompromised diabetic normotensive patient who presented to us with mild fever of and on and loss of appetite since 6 months. P/A- mild hepatosplenomegaly. Sonographical examination of the abdomen showed bilateral adrenal masses. His laboratory investigations are shown in [Table 1].
Table 1: Laboratory investigations

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He expired on day 2 of admission.

Clinical impression-metastatic adrenal nodules from an unknown site.

Autopsy findings

The autopsy showed that both adrenals were diffusely enlarged in volume; adrenals measuring 6 cm × 5 cm × 1 cm and weighing 120 g each [Figure 1] with extensive areas of parenchymal liquefying necrosis [Figure 2].
Figure 1: Bilaterally enlarged adrenals measuring 6 cm × 5 cm × 1 cm and weighing 120 g each

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Figure 2: Cut-surface of the adrenals showing extensive areas of liquefactive necrosis

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Spleen showed multiple 0.5-1 cm sized grayish white necrotic nodules throughout the parenchyma [Figure 3]. Liver- mildly enlarged. C/s-congested. Rest of the organs-unremarkable.
Figure 3: Spleen showing multiple 0.5-1 cm sized grayish white necrotic nodules throughout the parenchyma

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Microscopic examination of the adrenals showed extensive areas of parenchymal necrosis, brimming with yeast-forms of H. capsulatum both intra and extracellularly [Figure 4]. Inflammatory infiltrate was composed of neutrophils and macrophages. In the necrotic tissue, these several small fungal structures, at places arranged in grape-like clusters were Grocott stain-positive, [Figure 5].Similar fungal structures were also seen in the necrotic areas of the spleen and also in the lungs and kidneys.
Figure 4: H and E, section of adrenals showing extensive areas of parenchymal necrosis, brimming with yeast-forms of Histoplasma capsulatum both intra and extracellularly

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Figure 5: Grocott stain-positive several small fungal structures arranged in grape-like clusters seen in the necrotic areas

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  Discussion Top

We report a case history of an elderly patient with bilateral adrenal nodules and without adrenal failure. The diagnosis of histoplasmosis was established at the autopsy. While in young patients the disseminated form of the disease presents an acute and fulminating evolution, in the elderly the chronic progressive form is more frequently observed. [3] The frequency of the disseminated form is low; it is believed to be 1 in 1,000 cases. [4] Patients present with fever and nonspecific symptoms, followed by pancytopenia, elevated alkaline phosphatase levels. Several organs can be affected such as the lungs, gastrointestinal tract, bone marrow, central nervous system, lymph nodes and adrenal glands. [3] The dissemination occurs through the reticuloendothelial system. The diffuse involvement of the adrenals is common, but it can less frequently cause Addison's disease. This form of histoplasmosis is fatal when untreated. [5]

As for the related case, at ante-mortem, there was no clinical picture of adrenal insufficiency and were a sero-negative elderly male, the adrenal nodules were mis-diagnosed as metastasis to the adrenals.

In the elderly, histoplasmosis is usually severe and often occurs as the reactivation of a previously acquired latent infection. The case reports of histoplasmosis in the elderly show that the latency period can be quite long, varying from 10 [6] to 60 years. [7] The reactivation is commonly associated to an immunosuppressive disease, such as diabetes, but in some cases age is the only risk factor, probably due to a selective defect in the cell immunity against the histoplasm. [5]

Adrenal involvement in disseminated histoplasmosis is a frequent finding, being found in up to 80% of the patients who undergo abdominal computed tomographic or ultra-sonography, or those who die due to histoplasmosis. [7] Severo et al. [8] studying patients in Rio Grande do Sul, a southern state of Brazil, and Radin [2] studying patients in the USA, observed that adrenal involvement in the disseminated form is relatively more common in HIV-negative patients than in HIV-positive ones. Moreover, Kumar et al. described nine cases of adrenal histoplasmosis in India, all in HIV-negative patients. [9]

Although the adrenal involvement in disseminated histoplasmosis has been described in several reports, hypoadrenalism has been rarely reported. [10] Radiologically, the aspects of histoplasmosis lesions seem to depend on the disease stage and the presence of liquefying necrosis. The lesions generally present as a bilateral and symmetrical enlargement with preservation of the gland shape, peripheral enhancement, central hypodensity and calcifications. However, these findings are not specific, occurring with other disseminated infections, neoplasms and subacute hemorrhage. Tissue analysis may be required for a final diagnosis. [5]

Accordingly, in this case, at the autopsy active infection was seen in the adrenal glands and spleen. In the present report, unfortunately, during the patient's life, disseminated. Histoplasmosis was not suspected probably due to his clinical presentation.

  Conclusion Top

Disseminated histoplasmosis is not uncommon in India. In sero-negative individuals, immunosuppressive states like old age and diabetes is associated with reactivation of histoplasma infection.

It should be suspected when a person presents with prolonged fever, loss of appetite, hepatosplenomegaly and adrenal masses. Hence, histoplasmosis should always be included in the differential diagnosis of elderly diabetic patients with adrenal nodules.

Prompt diagnosis and treatment can help in salvaging such patients.

  References Top

Subramanian S, Abraham OC, Rupali P, Zachariah A, Mathews MS, Mathai D. Disseminated histoplasmosis. J Assoc Physicians India 2005;53:185-9.  Back to cited text no. 1
Radin DR. Disseminated histoplasmosis: Abdominal CT findings in 16 patients. AJR Am J Roentgenol 1991;157:955-8.  Back to cited text no. 2
Grover SB, Midha N, Gupta M, Sharma U, Talib VH. Imaging spectrum in disseminated histoplasmosis: Case report and brief review. Australas Radiol 2005;49:175-8.  Back to cited text no. 3
Umeoka S, Koyama T, Saga T, Higashi T, Ito N, Kamoto T, et al. High 18F-fluorodeoxyglocose uptake in adrenal histoplasmosis; a case report. Eur Radiol 2005;15:2483-6.  Back to cited text no. 4
Kauffman CA. Fungal infections in older adults. Clin Infect Dis 2001 15;33:550-5.  Back to cited text no. 5
Chedid MF, Chedid AD, Geyer GR, Chedid MB, Severo LC. Histoplasmosis presenting as addisonian crisis in an immunocompetent host. Rev Soc Bras Med Trop 2004;37:60-2.  Back to cited text no. 6
Giacaglia LR, Lin CJ, Lucon AM, Goldman J. Disseminated histoplasmosis presenting as bilateral adrenal masses. Rev Hosp Clin Fac Med Sao Paulo 1998;53:254-56.  Back to cited text no. 7
Severo LC, Oliveira FM, Irion K, Porto NS, Londero AT. Histoplasmosis in Rio Grande do Sul, Brazil: A 21-year experience. Rev Inst Med Trop Sao Paulo 2001;43:183-7.  Back to cited text no. 8
Kumar N, Singh S, Govil S. Adrenal histoplasmosis: Clinical presentation and imaging features in nine cases. Abdom Imaging 2003;28:703-8.  Back to cited text no. 9
Wheat J. Histoplasmosis. Experience during outbreaks in Indianapolis and review of the literature. Medicine (Baltimore) 1997;76:339-54.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1]


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