Final Diagnosis -- Follicular Hyperplasia with Focal Monocytoid B-Cell Proliferation

FINAL DIAGNOSIS:

Lymph node, right axillary, biopsy- Follicular hyperplasia with focal monocytoid B-cell proliferation, clusters of epithelioid histiocytes, and focal abscess formation

Warthin-Starry stain is positive for rod-like bacilli, strongly suggestive of cat scratch disease. Clinical correlation is required.

What is the criteria for a diagnosis of cat-scratch disease?

The clinical diagnosis of cat scratch disease can be made when three of the four following critteria are met (all four in an atypical case):

• Exposure to a cat and the presence of a scratch or primary dermal or eye lesion
• Positive cat scratch disease antigen skin test.
• Regional lymphadenopathy with negative culture results for other possible causes of lymphadenopathy ("sterile" pus aspirated)
• Characteristic changes in lymph node biopsy specimen

Clinical features of cat scratch disease:

• Most common cause of chronic benign lymphadenopathy in the US with approximately 24,000 cases per year
• Eighty-five percent of cases occur in patients under the age of 18 years, but can occur at any age
• A history of exposure to a cat is found in the majority of cases
• A skin papule associated with a cat scratch often precedes the onset of solitary lymphadenopathy 1 or 2 weeks later
• Disease is usually usually mild with associated fever and malaise, and is self-limited
• Up to 2% of patients experience severe manifestations including encephalopathy or bone and solid organ involvment
• Caused mainly by transmission of Bartonella henselae from cats to humans
• Occasiona cases of cat scratch disease caused by Afipia felis have been reported as well

Morphologic findings associated with cat scratch disease in the lymph node:

• Follicular hyperplasia with monocytoid B-cell population
• Small foci of necrosis with neutrophils, often within aggregates of monocytoid B-cells
• Hyperplastic paracortex
• Sinuses contain histiocytes, immunoblasts, and neutrophils
• Over time, foci of necrosis enlarge and coalesce and are surrounded by palisading histiocytes, forming the characteristic stellate abscesses
• Warthin-Starry stain coats the bacilli with silver granules making them larger and easier to identify
• Bacilli are most numerous in early lesions and can be found singly, in chains, or in large clumps, and absent in stellate abscesses

Bartonella henselae:

• Major arthropod vector is the cat flea (Ctenocephalides felis) for cat-to-cat transmission, but is not believed to be directly responsible for transmision to humans
• Contamination of cat claws by flea feces is hypothesized mechanism of transmission to humans
• Serologic studies indicate that B. henselae is globally endemic in cats (feral and domesticated) with prevalence of antibodies greater in warm and humid climates
• Bartonella henselae is also the causative agent of bacillary angimatosis

Identification of Bartonella henselae

By Culture:

• Can be cultured on cell-free media, including freshly prepared rabbit-heart-infusion agar plates, as well as various formulations of blood or chocolate agar
• Requires more than 7 days of incubation, therefore is not identified by routine culture protocols in clinical microbiology laboratories
• The presence of small curved weakly gram-negative bacilli, that are catalase negative, oxidase negative, requiring more than seven days incubation is highly suggestive of either
• Bartonella henselae or B. quintana (causative agent of trench fever)
• Antimicrobial susceptibility testing is usually not appropriate given its slow growth
• Generally, B. henselae is susceptible to most antibiotics in vitro, with the exceptions of nalidixic acid, and occasionally penicillin, ampicillin, tetracycline,or vancomycin.

By serology:

• Has largely replaced the practice of the antigen skin test
• Most are either immunofluorescence assays (IFA) or enzyme immunoassays (EIA) using bacterial whole cell antigens
• IFA and EIA has been shown to be superior to the antigen skin test
• Significant cross reactivity exists between B. henselae and B. quintana

By polymerase chain reaction (PCR) detection of B. henselae DNA:

• Higher sensitivity than serologic assays
• Assays directed against genes for either 16S ribosomal RNA, citrate synthase (gltA), or 60-kDa heat shock-like protein (htrA)
• Assay for 16S ribosomal RNA had the highest sensitivity (100%), versus for citrate synthase (94%), or 60-kDa heat shock-like protein (69%) (ref: Avidor B et al. J Clin Microbiol 35 :1924-1930)

REFERENCES

• Avidor B, et al. (1997) Molecular diagnosis of cat scratch disease: a two step approach. J Clin Microbiol 35:1924-1930.
• Avidor B, et al. (2001) DNA amplification for the diagnosis of cat-scratch disease in small-quantity clinical specimens. Am J Clin Pathol 115:900-909.
• Bergmans AMC, et al. (1995) Etiology of cat scratch disease: comparison of polymerase chain reaction detection of Bartonella (formerly Rochalimaea) and Afipia felis DNA with serology and skin tests. J Infect Dis 171:916-923.
• Bergmans AMC, et al. (1997) Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay. J Clin Microbiol 35:1931-1937.
• Ferry JA and Harris NL (1997) "Bacterial Infections", from Atlas of Lymphoid Hyperplasia & Lymphoma, L Day (Editor), Saunders, WB Company, pg. 17-21.
• Mouritsen CL, et al. (1997) Rapid polymerase chain reaction-based detection of the causative agent of cat scratch disease (Bartonella henselae) in formalin-fixed, paraffin-embedded samples. Hum Pathol 28:820-826.
• Relman DA, et al. (1990) The agent of bacillary angiomatosis: an approach to the identification of uncultured pathogens. New Engl J Med 323:1573-1580.
• Sander A, et al. (1999) Detection of Bartonella henselae DNA by two different PCR assays and determination of the genotypes of strains involved in histologically defined cat scratch disease. J Clin Microbiol 37 :992-997.
• Slater LN and Welch DF (1999) "Bartonella species, including cat-scratch disease", from Mandell, Douglas & Bennett's Principles & Practice of Infectious Diseases, JE Bennett, GL Mandell, R Dolin, RG Douglas (Editors), Saunders, WB Company, pg 2444-2456.

Contributed by Mark Fung, MD