Abstract
The introduction of screening mammograms has revolutionized the early detection of breast cancer. However, it remains the most common cancer in women in the United States, excluding skin cancer. As the incidence rates continue to rise, unusual presentations have become more frequent. Additionally, healthcare barriers can lead to delayed detection of breast cancer, resulting in unexpected complications. The occurrence of pyogenic liver abscess (PLA) in diabetic cancer patients, due to the synergistic effect of insulin-like growth factor-1 in tumorigenesis and abscess formation, is well documented. PLA is also prevalent in hepatocellular, colorectal, and pancreato-biliary tumors. However, the occurrence of PLA as an initial presentation of isolated advanced breast cancer without these comorbidities is understudied. This may be due to direct spread of infection from affected skin or spread via lymphatics or vasculature in the setting of immunosuppression from cancer. We present an exceedingly rare case of PLA, complicated by pulmonary embolism, in an elderly female with newly diagnosed stage IIIB breast carcinoma.
Introduction
Liver abscesses are defined as purulent masses caused by bacterial, fungal, parasitic, or amoebic infections. 1 These abscesses typically occur due to biliary disease, arterial hematogenous seeding, direct inoculation from infection or injury, and are predominantly localized to the right lobe of the liver. 2 Although the incidence of liver abscesses is low, they are the most common visceral abscesses, accounting for 48% of all visceral abscesses and 13% of all intra-abdominal abscesses in a study of 540 cases.3,4 The annual incidence rate of liver abscesses is approximately 2.3 per 100 000 people, with a higher occurrence in men than in women (3.3 vs 1.3 per 100 000). Significantly higher rates, up to 17.6 cases per 100 000, have been observed in East Asian countries. 3 Risk factors for liver abscesses include diabetes mellitus, preexisting hepatobiliary or pancreatic conditions, liver transplantation, and regular proton-pump inhibitor use. Additionally, geographic and individual factors, such as the primary invasive liver abscess syndrome linked to Klebsiella pneumoniae, play a role. 3
The development of liver abscesses involves a complex interaction of microbial invasion, host immune reactions, and inflammatory responses. Prompt identification and treatment, typically with antibiotics and drainage, are crucial for managing these infections. Several pathways can lead to the spread of infection to the liver, resulting in a pyogenic abscess. A large portion of pyogenic liver abscesses (PLAs) originate from bacteria coming from bowel leakage and peritonitis that travel to the liver via the portal vein. 5 Infection or insult to the biliary tract or from underlying biliary tract disease, such as gallstones or malignancy, is also a direct pathway. Additionally, polymicrobial infections in the systemic circulation may spread to the liver. 5 In rare instances, abscesses have been shown to develop from surgical or penetrating injuries, such as those caused by the migration of a swallowed foreign body. 6
Although the link between PLA and cancers, especially colorectal and other gastrointestinal cancers, is relatively rare, it is substantial enough to warrant consideration by clinicians of potential underlying cancers when diagnosing and managing these cases. PLA can occur as a complication of colorectal cancers through necrosis and infection of hepatic metastases or through an independent metastatic process. 7 Another rare association between PLA and gastric cancer is highlighted by the occurrence of hematogenous complications.8,9 A recent comprehensive population-based study shows higher occurrences of gastrointestinal cancers—including colorectal, small intestine, biliary tract, and pancreatic cancers—in patients with PLA. These findings indicate that PLA could serve as a marker or potential risk factor for underlying gastrointestinal malignancies. 10 PLAs are also found to be associated with nonmetastatic colorectal cancers, suggesting regional variability in microbial and clinical presentation. 11 While literature has shown a connection to various cancers, PLA as an initial sign of advanced breast cancer is exceptionally rare and poorly studied.
This case is unique because it involves a PLA resulting from the contiguous and hematogenous spread of Streptococcus anginosus bacteria from an infected, fungating breast cancer to the liver. The case also emphasizes the need to consider unconventional presentations in cancer diagnostics and highlights the importance of thorough management approaches for patients with complex clinical pictures.
Case Description
We report the case of a 73-year-old African-American female with a history of a right breast mass for 1 year presented with abdominal pain, dysphagia which is more with solids than liquids and diarrhea for 5 days. She reported unquantifiable but significant weight loss in the past year. Vital signs on admission were significant for temperature of 98.9F, heart rate 109 beats per minute, blood pressure 128/90 mmHg, respiratory rate 18 per minute, and saturating 99% on room air. Physical exam revealed a fungating, ulcerative right-sided breast mass 14 cm × 10 cm, which was immobile and fixed to skin and surrounding tissue. No palpable lymphadenopathy or hepatosplenomegaly appreciated. There was mild tenderness to palpation in the right upper quadrant. Laboratory workup on admission was significant for low hemoglobin of 5.6 g/dL, leukocytosis of 20 900 cells/mL (differential: 80.8% neutrophils, 12.6% lymphocytes, 0.2% basophils, 0.2% eosinophils and 6.2% monocytes), and thrombocytosis of 925 000 cells/mL. C-reactive protein was elevated to 273 mg/L (reference range: <5 mg/L). Liver enzymes were also noted to be high, aspartate aminotransferase 60 U/L, alanine transaminase 46 U/L and alkaline phosphatase to 174 U/L (Table 1). CT scan of the chest abdomen and pelvis with contrast showed a heterogeneously enhancing ulcerated right breast mass with axillary lymphadenopathy and bilateral segmental and subsegmental pulmonary emboli without evidence of right heart strain (Figures 1 and 2A). It also showed a 16 cm hepatic fluid collection with air fluid level in the right lobe of liver consistent with abscess with some suprahepatic and subhepatic collections representing additional loculated infections.
Relevant Laboratory Workup.
Abbreviations: H, high; L, low; GCDFP-15, gross cystic disease fluid protein 15; HER-2, human epidermal growth factor receptor 2.
CT chest findings on initial presentation showing breast mass, para-aortic lymphadenopathy, and pulmonary embolism; Blue arrow: Pulmonary embolism; Green arrow: Para-aortic lymph nodes; Red arrow: Breast mass.
(A) Hepatic abscess before drainage and (B) hepatic abscess after drainage. Red arrow: Breast mass; Yellow arrow: Liver abscess.
She was transfused 1 unit packed red blood cells to maintain haemoglobin more than 7 g/dL. Therapeutic low molecular weight heparin started for pulmonary embolism seen on CT scan after hemoglobin stabilisation. She underwent CT-guided drainage of hepatic abscess which drained 760 cc foul smelling thin brown fluid (Figure 2B). Fluid cultures from hepatic abscess (grown in Sheep’s blood agar, Lowenstein-Jensen media and Phenylethyl alcohol blood agar) grew Gemella morbillorum and S. anginosus. Mycobacterial infection was ruled out by AFB stain and culture. Fungal cultures were negative. Fluid cytology was negative for malignancy, but oncology advised that this is nonspecific for ruling out the malignancy.
Right breast mass biopsy was performed. Initial biopsy of the breast mass by surgery showed mucinous neoplasm but specimen was inadequate and was inconclusive. Repeat breast biopsy revealed well-differentiated invasive ductal carcinoma with mucinous features and was estrogen receptor positive and human epidermal growth factor receptor 2 negative (Figure 3A-C). Right axillary node biopsy also revealed invasive ductal carcinoma (Figure 4) and left axillary lymph node biopsy showed reactive lymph node tissue. Wound cultures were collected from the fungating breast mass, and she was given ceftriaxone, metronidazole, and linezolid. Antibiotic regimen was later changed to vancomycin, cefepime, and metronidazole as the cultures from breast mass grew pseudomonas, S. anginosus, and coagulase negative staphylococcus.
(A) Right breast biopsy: invasive ductal carcinoma with mucinous feature (H&E 40×); Red arrow: Mucinous feature.(B) Right breast biopsy: invasive ductal carcinoma with mucinous feature (H&E 100×); Red arrow: malignant cells. (C) Right breast biopsy: invasive ductal carcinoma with mucinous feature (H&E 400×); Red arrow: malignant cells.
Axillary lymph node biopsy: invasive ductal carcinoma with mucinous feature (H&E 100×); Red arrow: malignant cells.
Patient was treated with 2 weeks of intravenous antibiotics. Advised to follow-up with oncology outpatient for evaluation with PET scan and treatment of the invasive ductal malignancy and was discharged with 2 weeks of amoxicillin/clavulanic acid to complete a 4 week total antibiotic course for the liver abscess.
A repeat CT abdomen and pelvis 1 month later showed a 3.5 cm × 2.4 cm mild residual fluid collection which was previously 16.3 cm × 9.3 cm × 13.4 cm. Subsequent CT scans showed complete resolution of the abscess. PET CT showed evidence of ipsilateral axillary nodal metastasis and absence of distal spread. She was diagnosed with T4N1M0 (stage IIIb) invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy with dose-dense doxorubicin and cyclophosphamide for 4 cycles followed by weekly taxol for 12 cycles followed by neoadjuvant anastrozole. Right total mastectomy was performed, and adjuvant anastrozole was started. Radiation oncology and surgery follow-ups continued.
Discussion
This case presents several rare and unique findings, including a PLA resulting from the contiguous and hematogenous spread of S. anginosus bacteria from an infected, fungating breast cancer to the liver. Breast cancer, despite advances in early detection and treatment, remains the most common malignancy among women in the United States. 12 While the incidence of PLA in patients with breast cancer is low, it is more frequently reported in association with hepatocellular, colorectal, and pancreato-biliary tumors. 13 The occurrence of PLA in breast cancer patients is an unusual and underreported phenomenon, which warrants further exploration to understand its clinical implications and prevalence.
G. morbillorum, a Gram-positive anaerobic coccus, is an uncommon pathogen often found in the oral flora and as a commensal organism in the upper respiratory tract. 14 Although it is rarely implicated in severe infections, it has been associated with cases of endocarditis, osteomyelitis, and, as seen in this case, PLAs. 15 Its role in abscess formation may be linked to its ability to form biofilms and persist in tissue environments, coupled with its potential for hematogenous spread. 16 The rarity of this pathogen, combined with its association with complex infections, underscores the importance of considering less-common pathogens in differential diagnoses when managing severe infections.
The mechanism by which hepatic abscesses develop in the setting of breast cancer is complex and multifactorial. One potential pathway involves the immunosuppressive effects of the cancer itself, which can predispose patients to infections. 17 Additionally, direct spread of infection from the skin or other metastatic sites can lead to liver abscess formation. 18 This case illustrates such an uncommon route of infection, potentially involving both contiguous and vascular spread from an infected breast mass to the liver. The close anatomical relationship between the fungating right breast mass and the liver abscess, as demonstrated by CT imaging, represents a previously undocumented clinical association. Recognizing the potential for contiguous and vascular dissemination of infectious complications in immunocompromised cancer patients is essential, even when there is no direct involvement of the liver by the tumor. In the context of diabetes or other comorbidities, the risk is further heightened due to the synergistic effects of insulin-like growth factor-1 promoting both tumor growth and abscess formation. 19
The prognosis for patients with hepatic abscesses associated with breast cancer is generally guarded and depends on several factors, including the timely diagnosis and management of both the abscess and the underlying malignancy. 4 Complications, such as pulmonary embolism, as seen in this case, further complicate the clinical course and can significantly impact outcomes. 20 Prompt recognition and treatment of PLA are crucial for improving survival rates. However, the overall prognosis remains poor, particularly for patients with advanced-stage cancer and additional health challenges, such as poor health literacy, which can delay presentation and treatment. 21
Conclusion
Advanced breast cancer can present with a multitude of complications, including venous thromboembolism, sepsis, and cardiopulmonary failure. This case highlights the importance of recognizing a rare pathway involving the contiguous and vascular spread of infection from an infected breast mass to the liver. The proximity of the fungating mass on the right breast and the liver abscess, as revealed by the CT scan, underscores a unique clinical association not previously documented. When evaluating multifocal hepatic lesions, it is essential to consider this possibility of contiguous or vascular spread of infection from the affected breast skin before concluding it to be metastasis. This case also raises awareness of prevailing barriers in healthcare, which, if left unaddressed, could result in otherwise avoidable catastrophic outcomes. It serves as a critical reminder for healthcare providers to consider less-common pathways and unconventional presentations, ultimately emphasizing the need for thorough and timely diagnostic and treatment approaches to improve patient outcomes.
Footnotes
Acknowledgements
We would like to express our gratitude to the clinical staff at The Brooklyn Hospital Centre for their exceptional care and support during the management of the patient described in this case report. We also thank our colleagues for their insightful discussions and contributions to the development of this manuscript. Lastly, we appreciate the guidance and resources provided by the Institutional Review Board, which facilitated the ethical approval for publication.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics Approval
Permission to report this case was granted by the Institutional Review Board of The Brooklyn Hospital Center Number: 2263278.
Informed Consent
Written informed consent was obtained from the patient for their anonymized information to be published in this article.
Prior Presentation
This abstract is not previously presented at a meeting.
