Caseating Granulomatous Inflammation 2

Caseating Granulomatous Inflammation
Think beyond Tuberculosis

AUTHORS – Padmavati Devi Chaganti, YVS Prabhakar , KA Seetaram
Published in the International Journal of Phonosurgery and Laryngology,

July-December 2013;3(2):51-54
INTRODUCTION
• Immunocompromised state predisposes to several infections which
includes both bacterial and fungal.
• The causes of immunocompromised state range from conditions like

corticosteroid therapy to infections like human immunodeficiency virus
(HIV).
• Here, we are reporting a case of histoplasmosis diagnosed as

tuberculosis clinically and histopathologically in a HIV-positive patient.
CASE REPORT
A 33 years old male patient, a
known case of HIV infection and
on antiretroviral treatment for
more than 5 years, under regular
follow-up complained of fever
with progressive dyspnea,
productive cough with loss of
appetite and weight for about 2
months. Cervical lymphadenopathy
• Physical examination was unremarkable except for enlarged cervical
lymph nodes and no other lymph nodes or masses were felt.
• Laboratory investigations showed CD4 count of 56 and total leukocyte
count of 2,560 cells/cmm.
• X-ray of the chest showed cystic cavities hilar lymphadenopathy and
pleural thickening.
• Fine-needle aspiration cytology (FNAC) of cervical lymph node showed
caseating granulomatous inflammation, and a diagnosis of tuberculosis
was made and the patient was started on anti tuberculous treatment.
• The patient did not respond to antituberculous treatment even after 2
months and developed difficulty in swallowing with pain in throat.
• Systemic examination showed an
ulcer with nodules in the soft
palate.
• A differential diagnosis of drug
resistant tuberculosis, fungal
infection or malignancy was
considered.
• Biopsy was done from the edge of
the ulcer in oral cavity.
Microscopic examination showed
hyperplasic squamous epithelium
of the skin with ulceration. Nodules on soft palate
• Subepithelium showed ill-formed granulomas consisting of foamy
macrophages and epithelioid histiocytes.
• Acid-fast bacilli (AFB) staining of the lymph node lesion and oral lesion
were negative.
HIGH POWER VIEW OF GRANULOMATOUS

LOW POWER VIEW OF GRANULOMA
INFLAMMATION
• Periodic acid schiff (PAS) stain showed yeast forms less than 5 μ in macrophages
confirming the diagnosis of histoplasmosis.
PAS positivity – low power PAS positivity – high power

• The patient was treated with amphotericin B with a dose of 1 mg per kg body weight and
within 2 weeks, the oral ulcers healed completely and the lymphadenopathy resolved.
• He was started on itraconazole and remained symptom free.
DISCUSSION
• Histoplasma capsulatum is a dimorphic fungus.
• Histoplasmosis is a systemic disease contracted by inhalation of spores of
histoplasma capsulatum.
• Symptomatic disease occurs only in 10% of effected individuals.
• Symptomatic infection presents in three main forms that is acute
pulmonary, disseminated and chronic pulmonary forms.
• In 1985 the center for disease control added disseminated form to the
spectrum of conditions that characterizes the acquired immunodeficiency
syndrome.
• The pathogenesis of histoplasmosis is not properly understood.
• The organism enters the macrophages either through opsonization or by a
mechanism that appears to be specific to the fungus.
• The fungus dissociates through macrophages and spread to various organs
like liver spleen, lymph nodes, bone marrow and gastrointestinal tract.
• Histoplasma yeasts multiply and causes cell lysis and the products so
released cause the release of gamma interferon which induces epithelioid
granulomas with central caseous necrosis.
• Histoplasma spores multiply in the lungs especially if there is previous
lung injury.
• Acute pulmonary disease presents with influenza like symptoms.
• The initial injury is in the form of interstitial pneumonitis especially
associated with centrilobular emphysema.
• With treatment, the infection either may resolve or progress to
fibrocaseous lesion.
• Chronic and severe histoplasmosis is associated with pre-existing lung
diseases like emphysema and lung cavities.
• Mediastinal lymphadenopathy is not observed differentiating this lesion
from sarcoidosis.
• The sections from the lungs showed poorly formed epithelioid
granulomas with central area of caseous necrosis.
• There is minimal lymphocytic response and Langhan’s type of giant
cells are less in number.
• Microscopic examination of the caseous material was negative for
AFB.
• The Gomori’s methenamine silver staining or PAS stain shows the
typical intracellular parasites which are 4 μ in size with a
perinuclear halo.
• Plenty of intracellular and extracellular parasites are seen at the
periphery of necrotic areas.
• Gastrointestinal involvement occurs because of hematogenous
dissemination of the fungus.
• It can occur both in immunocompetent and immunosuppressed
individuals.
• A total of 30 to 60% of patients with disseminated histoplasmosis
presents with oral lesions and they are rarely primary manifestations of
the disease.
• Gastrointestinal histoplasmosis presents as ulcers or nodules on the
mucosa of oral cavity or the ileocecal junction or ascending colon along
with lymphadenopathy.
• Microscopic findings include lymphohistiocytic infiltrations. Well-
formed granulomas are rare.
• The diagnosis of fungus is confirmed by isolation of fungus from the
sputum, or from bronchoscopic aspiration and staining with Grocott-
Gomeri methenamine–silver staining technique.
• Confirmation is by culture on Sabouraud dextrose agar. Antibodies are
detected 2 to 6 weeks after infection.
• Patients with AIDS usually present with disseminated disease.
• Disseminated histoplasmosis present with symptoms resembling tuberculosis.
• The clinical features of disseminated histoplasmosis are fever, weight loss,
fatigue, respiratory complaints, hepatomegaly splenomegaly,
lymphadenopathy and bone marrow involvement.
• Other features include involvement of gastrointestinal tract, meninges and
cardiovascular system.
• Histoplasmosis, whether presenting as pulmonary involvement,
gastrointestinal or as disseminated form, both clinically and
histopathologically mimics tuberculosis.
• Liposomal amphotericin B has proved to be more effective than conventional
amphotericin because it is associated with less side effectives and better
therapeutic effects.
CONCLUSION
• All cases of caseating granulomatous inflammation in HIV-
positive cases have to be evaluated both by clinical methods and
by special stains for both tuberculosis and histoplasmosis.
Thank You

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Caseating Granulomatous Inflammation

Think beyond Tuberculosis

Published in the International Journal of Phonosurgery and Laryngology,

• The causes of immunocompromised state range from conditions like

• Here, we are reporting a case of histoplasmosis diagnosed as

HIGH POWER VIEW OF GRANULOMATOUS

PAS positivity – low power PAS positivity – high power

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