Journal of Cytology
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Year : 2021  |  Volume : 38  |  Issue : 2  |  Page : 104-105
Not all lymphadenopathy and dyspnea in retropositive represent tuberculosis

1 Department of Cytogenetics, Christian Medical College, Vellore, Tamil Nadu, India
2 Indira Gandhi Institute of Medical Sciences, Department of Pathology, Patna, Bihar, India
3 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India

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Date of Submission05-Feb-2021
Date of Decision01-Apr-2021
Date of Acceptance26-Apr-2021
Date of Web Publication11-May-2021

How to cite this article:
Patel BK, Singh AR, Siddaraju N. Not all lymphadenopathy and dyspnea in retropositive represent tuberculosis. J Cytol 2021;38:104-5

How to cite this URL:
Patel BK, Singh AR, Siddaraju N. Not all lymphadenopathy and dyspnea in retropositive represent tuberculosis. J Cytol [serial online] 2021 [cited 2023 Feb 2];38:104-5. Available from:

   Introduction Top

Lymphadenopathy in PLHA, that is, people living with HIV/AIDS (Human immunodeficiency virus/Acquired immunodeficiency syndrome) can be due to non-specific reactive change, infections, hematolymphoid, and rarely, non-hematolymphoid malignancies such as Kaposi sarcoma.[1] Among infections, tuberculosis comprises a comfortable majority.[2],[3] Non-tuberculous infections in PLHA such as histoplasmosis, toxoplasmosis, and cryptococcosis while not unknown, are rare (except suppurative) and even more so when considering clinical differentials for a combined presentation of generalized lymphadenopathy and dyspnea.[2],[4] Our example illustrates one such rare occurrence.

   Case History Top

A 16-year-old boy, a PLHA (with erratic drug compliance), was brought to the hospital for resting dyspnea and high fever. He had been having an increasing productive cough over a month with rapid deterioration over the last 2 days. On examination, he had multiple significant bilateral cervical nodes (largest: 2 cm) and palpable inguinal and axillary nodes. Bilateral diffuse fine crepitations and mild tender hepatosplenomegaly of 3 cm was present. A provisional diagnosis of disseminated tuberculosis or Pneumocystis carinii pneumonia was made and the patient was admitted for decreased oxygen saturation. He was provided oxygen by mask. His chest X-ray was suggestive of pulmonary edema. Blood counts revealed a pancytopenia. His CD4 count was 86/cc. The liver enzymes were mildly elevated (alanine and aspartate aminotransferase of 62 and 76 U/L respectively) with near-normal total bilirubin (1.3 mg/dL). His condition rapidly deteriorated overnight with increasing respiratory distress and he passed away from respiratory failure in the ICU within 10 hours of his admission. The largest node that had been aspirated antemortem showed paucicellular smears with a few lymphoid cells caught up in mucoid material with occasional loose clusters of predominantly non-epithelioid macrophages resembling ill-defined granulomas, rare osteoclastic giant cells, and innumerable extracellular yeast forms of variably sized fungal organisms with negative shadows giving a halo-like appearance around the cell walls on the May Grünwald Giemsa (MGG) stain [Figure 1]a and [Figure 1]b. Papanicolau stained smears showed similar findings [Figure 1]c. These were identified as Cryptococcus neoformans. Some narrow-based budding forms were also noted. A limited post-mortem biopsy of his lungs showed features of cryptococcal pneumonia with similar carminophilic fungi in the alveolar spaces [Figure 1]d.
Figure 1: (a) Extracellular variably sized cryptococci including occasional narrow, budding forms (black arrow). Negatively stained C cell wall and pericellular halo due to mucoid capsule are prominent (MGG stain, 400X). (b) An osteoclastic giant cell with many ingested cryptococci (MGG stain, 100X). (c) Orangeophilic cryptococci with green cell wall and capsule (Papanicolau stain, 400X). (d) Post-mortem lung biopsy showing an alveolus filled with rose colored carminophilic cryptococci (Mucicarmine stain, 100X)

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   Discussion and Differential Diagnosis Top

The causative organism of cryptococcosis is the fungus Cryptococcus neoformans that manifests primarily as pneumonia or meningoencephalitis mostly among immunocompromised individuals. Notably, only extrapulmonary cryptococcosis is considered an AIDS-defining illness since the organisms may be acquired by inhalation of soil heavily contaminated with pigeon droppings in even immunocompetent individuals. Disseminated disease occurs from weakened immunity or immune reconstitution.[1],[4] Even among the extrapulmonary disseminated forms, cryptococcal lymphadenitis is so uncommon that only scattered reports exist with the largest series (to the best of our knowledge) comprising only 15 patients.[5]

Indeed, clinicians unsurprisingly tend to start empirical antituberculous therapy in retropositive lymphadenopathy. Rapid and reliable laboratory confirmation is, therefore, imperative for the rarer diagnoses. It is here that the role of fine needle aspiration cytology as an adjunct diagnostic tool is envisioned since the latex agglutination and antibody-based testing while highly accurate are not foolproof. For example, false negatives due to low organism load and false positives due to prozone phenomena, rheumatoid factor, or mimicry with related pathogens are well known.[6]

Cytologic diagnosis of Cryptococcus is thankfully straightforward for a trained eye looking out for the thick mucopolysaccharide and carminophilic capsule reminiscent of soap bubbles on the MGG stain. Rhinosporidium seeberi and Blastomyces dermatidis are the only two other fungi known to be positive for mucicarmine. While Rhinosporidium is morphologically distinct with large spherules holding numerous sporangia, Blastomyces sp. is more likely to pose a diagnostic dilemma. However, Blastomyces sp. in contrast to Cryptococcus show broad-based budding, are generally larger 8–15 μ versus the variably sized yeast forms of Cryptococcus (average: 5 μ, range: 2–15 μ), are weakly carminophilic (due to a thin to absent cell wall), are never Masson Fontana positive, and only extremely rarely affect lymph nodes.[4] Candidiasis, histoplasmosis, coccidiodomycosis, and paracoccidiodomycosis are the other potential loopholes but the organisms lack the mucopolysaccharide capsule. Besides a confident illustration of the organism on smear, other elements of smear evaluation add little value. For example, granulomas, giant cells, necrosis, and reactive lymphoid background may be seen in tuberculosis as well. Mucinous background reflective of the mucinous pattern on histopathology seems a worthy exception theoretically but in practice is exceedingly rare, since none of our cited references including a review of 15 patients seem to mention it.[4],[5]

   Conclusion Top

We share the case mainly to sensitize practicing cytopathologists about this rare presentation. Equally crucial is the message that a diligent search for organisms, routine acid-fast staining, and rapid on-site evaluation of aspirates is a sine qua non in PLHA patients. This could salvage precious time and save lives.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Dogbey P, Golden M, Ngo N. Cryptococcal lymphadenitis: An unusual initial presentation of HIV infection. BMJ Case Rep 2013;2013:bcr2013010316.  Back to cited text no. 1
Jayaram G, Chew MT. Fine needle aspiration cytology of lymph nodes in HIV-infected individuals. Acta Cytol 2000;44:960-6.  Back to cited text no. 2
Sun L, Zhang L, Yang K, Chen XM, Chen JM, Xiao J, et al. Analysis of the causes of cervical lymphadenopathy using fine-needle aspiration cytology combining cell block in Chinese patients with and without HIV infection. BMC Infect Dis 2020;20:224.  Back to cited text no. 3
Bhuyan P, Pattnaik K, Kar A, Brahma RC, Mahapatra S. Cryptococcal lymphadenitis in HIV: A chance diagnosis by FNAC. Diagn Cytopathol 2013;41:456-8.  Back to cited text no. 4
Srinivasan R, Gupta N, Shifa R, Malhotra P, Rajwanshi A, Chakrabarti A. Cryptococcal lymphadenitis diagnosed by fine needle aspiration cytology: A review of 15 cases. Acta Cytol 2010;54:1-4.  Back to cited text no. 5
Xu XG, Bi XL, Wu JH, Xu H, Liao WQ. Disseminated cryptococcal lymphadenitis with negative latex agglutination test. Chin Med J (Engl) 2012;125:2393-6.  Back to cited text no. 6

Correspondence Address:
Dr. Bidish K Patel
Department of Cytogenetics, Christian Medical College (CMC), Vellore - 632 004, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/JOC.JOC_17_21

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