Article Text


Abnormal behaviour in a man with massive, generalised, peripheral lymphadenopathy

Statistics from

Q1: What are the diagnoses?

The diagnoses are disseminated cryptococcosis with meningoencephalitis and massive generalised lymphadenopathy, intestinal cryptosporidiosis, and oropharyngial candidiasis in advanced HIV disease.

Q2: What is unusual and atypical in the case illustrated?

The following features are unusual for classical meningitis:

  • Absence of positive indicators of meningitis like neck rigidity.

  • Normal concentrations of glucose and protein and absence of pleocytosis in the CSF. Thus absence of neck stiffness and absent CSF pleocytosis does not necessarily rule out fungal meningitis; this underscores the need for high clinical suspicion in the immunocompromised host.

  • Massive peripheral lymphadenopathy is rare in cryptococcosis.

  • The absence of respiratory involvement in disseminated cryptococcosis, despite the lung being the portal of entry for cryptococcus, is an unusual feature.

  • FNAC of the lymph node has proved in this case to be a very simple, reliable, and rapidly useful diagnostic test in evaluating cryptococcal lymphadenopathy.


Cryptococcus neoformans is by far the most common, potentially fatal fungal pathogen in patients with HIV infection.1 It accounts for approximately 5%–10% of all opportunistic infections in patients with HIV disease. The lung, brain, and meninges are the most frequently involved sites in systemic cryptococcosis.2 Subacute meningitis with or without encephalitis is the most common clinical form followed in frequency by pulmonary infections and disseminated infection.1 3

Cryptococcal meningitis in the immunocompromised host often presents with subacute, non-specific symptoms referable to the central nervous system such as headache, nausea, dizziness, irritability, somnolence, clumsiness, confusion, and impaired memory and judgment.3 4

Learning points

  • Generalised lymphadenopathy is an unusual presentation of cryptococcosis.

  • Cryptococcal lymphadenopathy usually suggests a widely disseminated form of cryptococcosis.

  • Clinically cryptococcal meningitis in the immunecompromised host may present with atypical, non-specific features, sometimes without positive meningitis indicators and absent CSF pleocytosis. A high index of clinical suspicion would help in early diagnosis.

  • Latex agglutination test for CSF CRAG has both diagnostic and prognostic values. It is a good guide in monitoring therapy.

  • FNAC of the lymph node is a very simple, reliable, and rapidly useful diagnostic test in evaluating cryptococcal lymphadenopathy.

Positive meningitis indicators may not be present, as in our patient, who had no meningeal signs. This underscores the significance of CSF analysis when fever and constitutional symptoms alone are reported by patients with advanced HIV disease especially when the serum levels of cryptococcal antigen (CRAG; not done on our patient) titres are raised. It is well known that the latex agglutination test for CSF-CRAG5-7 is a rapid, reliable, and sensitive confirmatory diagnostic test for cryptococcal meningitis in patients with normal CSF findings (our patient had normal values for glucose and protein in CSF without pleocytosis). However our patient did not have the latex agglutination test. Gram stain of CSF showed large budding cells and India ink stained rounded cells with clear haloes. CSF showed cryptococci on culture. Thus normal CSF findings in HIV disease do not exclude cryptococcal meningitis if clinical suspicion is high. An abnormal sensorium, leucocyte count in the CSF of <2.0 × 107/l, and CSF CRAG of >1:1024 are some of the factors that place the HIV patient at higher risk of meningitis related complications and relapse.1 CSF antigen titres will fall with antifungal therapy, thus the latex test is useful in monitoring therapy, besides being a screening test.1 Occasional false positive results with the latex agglutination test could be due to rheumatoid factors and other interference factors.6 Rarely immune complexes with CRAG could cause artificially low titres with the use of the latex agglutination test.6

Extraneural cryptococcosis commonly presents with pulmonary disease or cryptococcaemia with subacute constitutional symptoms. Though myocarditis with acute heart failure, mediastinal involvement mimicking lymphoma, cryptococcosis of the skin, eyes, and sacrum have been reported, massive and generalised cryptococcal peripheral lymphadenopathy in combination with cryptococcal meningitis, in the absence of extensive pulmonary lesions has not been reported in the medical literature.8 Involvement of lymph nodes is usually seen where the disease is very widely disseminated.9 FNAC of the cervical lymph node showed sheets of lymphocytes, histiocytes, occasional plasma cells, and macrophages. Encapsulated spherical/ovoid organisms ranging from 4–8 microns with narrow based budding were identified both intracellularly and extracellularly within the histiocytes. The yeast forms had mucicarminophilic capsules and stained with periodic acid Schiff and Gomori's methenamine silver. Aspirate from the lymph node showed cryptococci on culture. Thus FNAC of the lymph node is a very simple and a rapidly useful diagnostic screening test in the evaluation of cryptococcal lymphadenopathy.10 11

The figure (p 474) shows (A) soap bubble appearance of cryptococci in FNAC of lymph node, (B) polysaccharide capsule showing as clear halo around the rounded budding cryptococci in the CSF sample, (C) intracellular cryptococci budding in FNAC of lymph node, and (D) cryptococci budding (arrows) in FNAC of lymph node.

Final diagnosis

Advanced HIV disease with disseminated cryptococcosis, cryptococcal meningoencephalitis, generalised peripheral lymphadenopathy and oropharyngial candidiasis, and intestinal cryptosporidiosis.


View Abstract

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.