December 2009
Written by Peter M. Banks, M.D., Director of Hematopathology, Carolinas Medical Center, Charlotte, North Carolina.

Submitting Physician
David A. Weinrib, M.D., Division of Infectious Disease, Department of Internal Medicine, Carolinas Medical Center, Charlotte, North Carolina.

Diagnosis
Mycobacterium avium complex involving sampled para-aortic lymph node as so-called histiocytic pseudotumor.

Clinical History
A 28 year old male known to be HIV-positive had been on anti-viral therapy for about 3 months with progressing disseminated retroperitoneal lymph node enlargement with fever and lassitude. A directed needle biopsy was obtained.

Microscopy
Conventional H&E-stained sections show most of the sample to consist of pale blue-gray tissue with only small foci of dark blue residual lymphoid elements (see Figure 1).

At high magnification the process can be seen to consist of histiocytes, and even with just the H&E stain at very high magnification one can perceive a linear granularity within the cytoplasm (see Figure 2).

Ancillary Studies
Special stains, both acid-fast (Ziehl-Neelsen method) and periodic-acid-Schiff (PAS), demonstrate dense arrays of long bacillary organisms. Even with a Giemsa stain there is a staining pattern suggesting the presence of these bacilli (see Figure 3).

After four weeks of culture in Lowenstein-Jensen medium there was growth of colonies, and these were then confirmed to be M. avium complex by DNA probe methodology (courtesy of Robert Sautter, Ph.D., Director of Microbiology, Carolinas Medical Center).

Discussion
Mycobacterial species other than M. tuberculosis are generally considered opportunistic infectious agents, in that they are normally present in abundance in our environment and yet do not produce human disease among individuals with normal immune systems. Mycobacterium avium and m. intracellulare are closely related species, difficult to distinguish one from the other, even with culture characterization, so that current usage is to group the two together as M. avium complex. Prior to the modern era of iatrogenic immunosuppression and human immunodeficiency viral infection these organisms were identified in human disease only as low grade chronic pulmonary infections in patients with predisposing factors such as chronic obstructive pulmonary disease.

In modern times these organisms have become a threat to immunodeficient hosts, with either pulmonary or gastrointestinal ports of entry. Most typically they concentrate in lymph nodes, where the accumulation of organisms in macrophages can clinically simulate neoplasms (1). Indeed, so abundant are the histiocytes in these lesions, they can be mistaken for metabolic storage diseases (2). Because of the patient setting of immunodeficiency, often with associated constitutional symptoms, malignant lymphoma is a prime differential diagnosis. Lesions can occur in isolation in extranodal sites, such as brain, resembling primary lymphoma in the immunodeficiency setting (3).

M. avium complex organisms are ideal for microscopic identification. They are very large and are avidly stainable, not only with acid-fast stains, but also with stains which detect carbohydrate elements in their cell walls, such as PAS and silver stains. If the pathologist includes this distinctive infectious agent in the initial differential diagnosis, even small samplings from needle aspiration procedures will allow a definitive diagnosis (4).

References

1. Wolf DA, Wu CD, Medeiros LJ.
   Mycobacterial pseudotumors of lymph node. A report of two cases diagnosed at the time ofpresentation using touch imprint preparations. Arch Pathol Lab Med. 1995; 119: 811-814.
2. Dunn P, Kuo MC, Sun CF.
   Pseudo-Gaucher cells in mycobacterial infection: a report of two cases. J Clin Pathol. 2005; 58: 1113-1114.
3. Morrison A, Gyure KA, Stone J, Wong K, McEvoy P, Koeller K, Mena H.
   Mycobacterial spindle cell pseudotumor of the brain: a case report and review of the literature. Am J Surg Pathol. 1999; 23: 1294-1299.
4. Ellison E, Lapuerta P, Martin SE.
   Fine needle aspiration diagnosis of mycobacterial lymphadenitis. Sensitivity and predictive value in the United States. Acta Cytol. 1999; 43: 153-157.

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