Final Diagnosis -- Follicular Hyperplasia with Focal Monocytoid B-Cell Proliferation
Lymph node, right axillary, biopsy-
Follicular hyperplasia with focal monocytoid B-cell proliferation, clusters of epithelioid histiocytes, and focal abscess formation
Final diagnosis comment:
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
- 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
- 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.
- 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)
- 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