Atypical Cause of Breast Mass and Lymphadenopathy

A 34-year-old woman with a positive family history of breast cancer presents with a palpable mass in the left lateral upper quadrant of the chest with ipsilateral palpable axillary lymphadenopathy. Her mother was diagnosed with breast cancer at age 66 years. She denies associated fever, chills, night sweats, weight loss, breast pain, nipple discharge, or other breast changes. Workup of the concerning area includes breast ultrasonography, which shows a 12 x 12 mm hypoechoic lesion. Mammography is deferred and, instead, magnetic resonance imaging (MRI) is performed, which shows a lesion with thin, marginal spiculation. The lesion is classified as Breast Imaging Reporting and Data System (BI-RADS) category 4, indicating that it is suspicious for malignancy and that further workup with a breast biopsy is recommended.   

Making the Diagnosis

In patients who present with lymphadenopathy, malignancy must be ruled out using imaging and biopsy.^1,2 In this patient, the suspected malignancy is breast cancer. In patients under 40 years old, ultrasonography is the preferred breast imaging modality because younger patients tend to have denser breast tissue that may obscure tumors if mammography is utilized.³ For patients older than 40 years, a mammogram can be ordered and the results can be used to determine if a biopsy is warranted based on the BI-RADS classification scoring (Figure).⁴ Other imaging modalities that may aid in the diagnosis include computed tomography (CT), MRI, and positron emission tomography (PET) scans.

Figure. BI-RADS Categories⁴

Category	Definition
0	Incomplete: additional imaging is necessary to adequately evaluate
1	Negative: normal imaging results
2	Benign findings
3	Probably benign findings: follow up with imaging in 6-12 months then regularly until the finding is considered stable
4	Suspicious abnormality: biopsy should be considered 4A: low likelihood of being cancer 4B: moderate likelihood of being cancer 4C: high likelihood of being cancer
5	Highly suggestive of malignancy
6	Known biopsy-proven malignancy

A breast mass and lymph node biopsies were performed and found necrotizing granulomas, ruling out a diagnosis of breast cancer. Necrotizing granulomas are associated with necrotizing granulomatous lymphadenitis. A pathology report indicating necrotizing granulomas should also raise suspicion for other diagnoses including but not limited to sarcoidosis, tuberculosis, lymphoma, fungal infections, bacterial adenitis, and cat scratch disease (CSD). Therefore, patients with regional lymphadenopathy should be asked if they have had any contact with animals to rule out animal-to-human transmissible diseases such as CSD, bubonic plague, and tularemia.⁵

After further follow-up questioning of the patient, concern was raised for CSD. The next step was to test for Bartonella henselae, the bacteria responsible for CSD, using a Warthin-Starry silver stain.⁵ Other serology tests that can be ordered include immunoglobulin G (IgG), IgM, and polymerase chain reaction (PCR) for B henselae.⁵ Laboratory testing for B henselae has poor sensitivity and specificity, often having a cross-reactivity with B quintana, the bacteria that causes trench fever.⁵ However, it is still important to obtain laboratory testing after making a clinical diagnosis of CSD.

Cat Scratch Disease Diagnostic Criteria

Diagnosis of cat scratch disease is made in patients with 3 out of the following 5 criteria⁶:

1. Contact with animals and presence of scratch or cutaneous primary lesion
2. Presence of regional lymphadenopathy
3. Ruling out other causes of lymphadenopathy with serology/culture tests
4. Positive intradermal test with specific antigen
5. Expected histopathologic changes in examined lymph nodes

The patient lives with a cat, presents with a minor scratch on her left arm, and has left axillary lymphadenopathy; additionally, her lymph node biopsy showed expected histopathologic changes consistent with CSD. All of these factors lead to a working diagnosis of CSD. The diagnosis was later confirmed with a positive IgM serology test for B henselae, indicating an acute infection of CSD.

Discussion

Cat scratch disease is a bacterial infection that can spread from cats to humans through an open wound, bite, or scratch.⁵ The disease presents 3 to 30 days after the initial inoculation with a mild infection around the site.⁵ The most common sign is regional lymphadenopathy; however, fever, fatigue, headache, and decreased appetite also may occur.⁷ A study by Iannace et al found that the most involved lymph nodes were the axillary, supraclavicular, anterior cervical, preauricular, epitrochlear, inguinal, and femoral lymph nodes.⁶ Cats contract B henselae from fleas, and it is estimated that approximately 40% of cats have exposure to the bacteria at some point in their lives but most cats do not have symptoms.⁷ Kittens younger than 1 year are more likely to spread B henselae to humans because of their more playful nature.⁷

Treatment of Cat Scratch Disease

Antimicrobial treatment should be considered for patients with lymphadenitis from CSD.⁵ Although CSD is self-limited in most patients, the presence of lymphadenitis is concerning for systemic involvement and treatment ensures the prevention of serious complications. In clinical studies, most patients were given azithromycin as antibiotic treatment, but others were given rifampin, amoxicillin, fluoroquinolones, or tetracyclines as alternative antibacterial therapies. It is recommended that patients with lymphadenitis receive 5 days of azithromycin.⁵ The alternative therapy is doxycycline twice a day in combination with rifampin twice a day for 5 days. However, if the lymph nodes become erythematous with purulent discharge, needle aspiration is the best treatment.⁹

In this patient scenario, malignancy was ruled out before starting antibiotic therapy. Because CSD presenting as a breast mass is rare, providers may not think to order serology testing for B henselae initially.^6,8 The incidence of breast cancer increases with age and, therefore, if a woman over 40 years presented with a breast mass and lymphadenopathy, a surgeon may choose to excise the mass while obtaining lymph node samples for pathology. Antibacterial therapy would still be given if pathology revealed CSD as the etiology, but the diagnostic and treatment approach may be more aggressive in older individuals if malignancy is suspected.⁸

As primary care providers, it is important to evaluate for life-threatening conditions such as malignancy first in any patient presenting with a suspicious mass, with or without lymphadenopathy, before exploring other diagnoses.

Kar Lin, MPA, PA-C, is a physician assistant at Premier Primary Care in Smyrna, GA; E. Rachel Fink, MPA, PA-C, is an assistant professor and associate director of admissions in the Physician Assistant Program at Augusta University in Augusta, Georgia. She also practices at Augusta Urology Associates.

References

1. Dhal U, Hicklen RS, Tarrand J, Kontoyiannis DP. Cat scratch disease as a mimicker of malignancy. Open Forum Infect Dis. 2021;8(11):ofab500. doi:10.1093/ofid/ofab500

2. Dwan D, Baker CM, Zhang SC, Black CC, Zuurbier RA, diFlorio-Alexander RM. Atypical cat-scratch disease: a radiology-pathology correlation. Breast J. 2020;26(4):786-787. doi:10.1111/tbj.13581

3. Geisel J, Raghu M, Hooley R. The role of ultrasound in breast cancer screening: the case for and against ultrasound. Semin Ultrasound CT MR. 2018 Feb;39(1):25-34. doi:10.1053/j.sult.2017.09.006

4. Understanding your mammogram report. American Cancer Society. Updated January 14, 2022. Accessed March 27, 2023. https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/mammograms/understanding-your-mammogram-report.html 

5. Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10-52. doi:10.1093/cid/ciu444.

6. Iannace C, Lo Conte D, Di Libero L, et al. Cat scratch disease presenting as breast cancer: a report of an unusual case. Case Rep Oncol Med. 2013;2013:507504. doi:10.1155/2013/507504

7. Cat scratch disease. Centers for Disease Control and Prevention. Updated January 17, 2020. Accessed March 27, 2023. https://www.cdc.gov/healthypets/diseases/cat-scratch.html 

8. Marques LC, Pincerato K, Yoshimura AA, Andrade FEM, Barros ACSD. Cat scratch disease presenting as axillary lymphadenopathy and a palpable benign mammary nodule mimicking a carcinoma. Rev Soc Bras Med Trop. 2018;51(2):247-248. doi:10.1590/0037-8682-0362-2016

9. Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D. Recommendations for treatment of human infections caused by Bartonella species. Antimicrob Agents Chemother. 2004 Jun;48(6):1921-33. doi:10.1128/AAC.48.6.1921-1933.2004