Understanding a Complex Case: A 59-Year-Old Woman with Aphasia, Anemia, and a Large Breast Mass

Table of Contents

• Case Presentation: Initial Symptoms and Findings
• Patient History and Background
• Differential Diagnosis: What Could This Be?
• Diagnostic Approach and Testing
• Pathological Findings and Final Diagnosis
• Treatment Plan: Radiation and Medical Oncology
• Clinical Implications for Patients
• Limitations and Considerations
• Recommendations for Patients
• Source Information

Case Presentation: Initial Symptoms and Findings

A 59-year-old woman arrived at a multidisciplinary breast oncology clinic for evaluation of a long-standing breast lesion that had been growing for many years. Three weeks before this evaluation, she had been admitted to another hospital with concerning symptoms including fever, confusion, and word-finding difficulties (aphasia). During that initial presentation, medical staff noted she was inattentive and disoriented, with mild expressive aphasia but no motor deficits.

Doctors observed a large, bleeding exophytic mass (growth protruding from the skin) in her right breast. Imaging studies provided critical information about her condition. A computed tomography (CT) scan of her head showed a wedge-shaped area consistent with an acute infarction (stroke) in the left temporoparietal region of her brain.

Laboratory tests revealed significant abnormalities in her blood counts. Her hemoglobin level was critically low at 4.3 g per deciliter (normal range: 11.0 to 15.0), indicating severe anemia. Her mean corpuscular volume was 69.7 fl (normal: 80.0 to 100.0), suggesting microcytic anemia, and her platelet count was elevated at 922,000 per microliter (normal: 130,000 to 400,000).

Further imaging with CT scans of her chest, abdomen, and pelvis revealed the extensive nature of her breast mass. The tumor measured 14.9 cm by 16.2 cm by 20.0 cm, appearing as both cystic (fluid-filled) and solid components. The scans also showed prominent lymph nodes in multiple areas and suspicious lesions in her ribs and lungs that could indicate metastatic disease (cancer spread to other organs).

Patient History and Background

The patient reported first noticing a palpable lesion in her right breast when she was 32 years old - approximately 27 years before her current presentation. She had pursued some evaluation with breast imaging at that time and recalled being told the lesion was benign. No biopsy had been performed initially.

For the intervening 27 years, the patient had received limited medical care. She attributed this lack of medical attention to ongoing demands of caring for her young child and various personal and work stressors. She reported that the breast lesion had grown slowly but steadily during those years, with more rapid growth occurring approximately 2 years before her presentation.

This accelerated growth was accompanied by skin breakdown, discomfort, and drainage that the patient initially thought might be related to chronic infection. Her medical history included menarche (first period) at age 10 and menopause at age 50. She had one pregnancy and had used hormonal contraception for 15 years during her lifetime, but never received hormone replacement therapy.

At the time of presentation, her performance status was rated as 1 on the Eastern Cooperative Oncology Group scale (where 0 is fully active and 5 is deceased). She had a family history of breast cancer in her maternal aunt. She lived in New England with her adult son and operated a small business. She reported occasional alcohol use but no cigarette smoking.

Differential Diagnosis: What Could This Be?

The medical team considered multiple possibilities for this long-standing, slow-growing breast mass. The differential diagnosis included both malignant (cancerous) and benign (non-cancerous) processes.

Common breast cancer types were evaluated:

• Hormone receptor-positive (HR-positive) cancers: Account for approximately 70% of breast cancers, driven by estrogen-dependent signaling pathways
• HER2-positive cancers: Represent about 20% of breast cancers, dependent on HER2 pathway activation
• Triple-negative breast cancers: Account for approximately 10% of invasive breast tumors, negative for estrogen receptors, progesterone receptors, and HER2 overexpression

The extremely prolonged 27-year course made some diagnoses less likely. HER2-positive and triple-negative breast cancers typically wouldn't show such prolonged growth without more severe systemic symptoms or metastatic spread earlier in the disease process. The presentation was also atypical for common benign lesions including fibroadenomas, cysts, abscesses, or fat necrosis.

Other considered possibilities included:

• Phyllodes tumors (a type of fibroepithelial lesion that can grow slowly over time)
• Various sarcomas (which can be locally progressive without systemic spread)
• Adenoid cystic carcinomas (typically slow-growing lesions with limited metastatic potential)
• Metastatic lesions from other primary cancer sites

The medical team also considered psychiatric factors that might contribute to delayed care, but found the patient had normal mental status, appropriate insight, and normal social functioning despite expressing some distrust of the medical system.

Diagnostic Approach and Testing

All patients with neglected breast lesions from presumed invasive processes require comprehensive evaluation. The standard approach includes systemic imaging for tumor staging and tissue sampling for definitive diagnosis.

When abnormal lymph nodes or suspicious lesions outside the breast are identified, additional tissue sampling in these areas is considered for complete staging, prognostic information, and treatment planning. Locally advanced tumors like this one often have complications including progressive pain, bleeding, and superimposed infection that may require additional interventions.

For this patient, the diagnostic process included multiple imaging studies and a biopsy. The initial incisional biopsy of the breast mass was performed under local anesthesia during her hospitalization. The pathological results would be critical for determining the exact cancer type and guiding appropriate treatment decisions.

Before definitive biopsy results were available, the medical oncology team considered low-grade, HR-positive, HER2-negative breast cancer as the statistically most likely diagnosis based on the slow growth pattern. However, less common invasive processes including sarcoma and adenoid cystic carcinoma remained strong possibilities in the differential diagnosis.

Pathological Findings and Final Diagnosis

The incisional biopsy of the breast mass provided definitive answers about the nature of this long-standing tumor. The pathological examination revealed carcinoma with a cribriform pattern (showing a sieve-like appearance) that was infiltrating the dermis, with myxoid material (gelatinous substance) present within the lumen.

Special immunohistochemical staining helped distinguish between possible diagnoses:

• Staining was positive for p63 in the intact myoepithelial cell layer
• Positive for CD117 in luminal epithelial cells
• Positive for MYB, a characteristic finding in adenoid cystic carcinoma

These findings confirmed the two-cell population typical of adenoid cystic carcinoma and ruled out cribriform carcinoma. Additional breast cancer biomarker studies were negative for estrogen receptor, progesterone receptor, and HER2 - making this a triple-negative cancer but with the specific pattern of adenoid cystic carcinoma.

The final pathological diagnosis was adenoid cystic carcinoma of the breast, a rare subtype accounting for less than 1% of all breast cancers. This diagnosis explained the unusually slow growth pattern over 27 years, as this cancer type is typically indolent (slow-growing) with limited metastatic potential compared to more common breast cancer types.

Treatment Plan: Radiation and Medical Oncology

Upon diagnosis, the medical team determined the patient couldn't safely manage basic wound care and dressing changes at home due to the risk of life-threatening bleeding. Given the locally destructive nature of the tumor and ongoing risks of bleeding and infection, a collaborative multidisciplinary treatment plan was developed.

Radiation Oncology Approach: The patient received urgent radiation therapy with three primary goals: achieving hemostasis (bleeding control), local tumor control, and conversion to a resectable disease state. She received three-dimensional conformal photon radiation therapy administered 5 days per week over a 7-week period for a total dose of 70 Gy in 35 fractions.

She also received concurrent cisplatin chemotherapy. The radiation targeted the breast, chest wall, and axilla on the right side using a tangential beam arrangement. Based on the low incidence of nodal spread in adenoid cystic carcinoma, elective nodal radiation beyond the axilla wasn't administered.

Adjacent skin areas not involved by tumor were treated with topical mometasone to reduce radiation-induced skin reactions. Toward the end of treatment, tumor malodor was managed with topical metronidazole cream. The patient experienced expected side effects including breast tenderness, skin redness (erythema), and focal moist desquamation (skin peeling).

Staging and Prognosis: The patient was diagnosed with stage IV adenoid cystic carcinoma of the breast (cT4b, cNX, cM1). Lymph-node involvement was considered equivocal, as lymph node involvement is very unusual in the cribriform variant of adenoid cystic carcinoma. The visible lymph nodes on CT scan may have represented reactive lymphadenopathy rather than cancer spread.

Clinical Implications for Patients

This case illustrates several important clinical implications for patients facing breast health concerns. The 27-year duration of symptom neglect highlights how personal circumstances, distrust of medical systems, and life stressors can create barriers to seeking timely medical care.

The case demonstrates that even extremely slow-growing breast abnormalities require medical evaluation. While adenoid cystic carcinoma typically has a better prognosis than more common breast cancer types, the extensive local growth in this case created serious complications including severe anemia from bleeding and neurological symptoms from a stroke possibly related to her overall medical condition.

This presentation also shows that rare breast cancer types can present differently than more common forms. The triple-negative status (negative for estrogen receptor, progesterone receptor, and HER2) would typically suggest a more aggressive cancer, but the adenoid cystic variant follows a different biological pattern with typically slower progression.

The multidisciplinary approach used in this case - involving medical oncology, radiation oncology, surgical oncology, and other specialists - highlights the importance of comprehensive care for complex cancer presentations, especially those with rare histologies that may require specialized treatment approaches.

Limitations and Considerations

Several important limitations and considerations emerge from this case study. As a single case report, the findings represent one patient's experience and may not be generalizable to all patients with similar conditions.

The extremely prolonged 27-year course before diagnosis is highly unusual, even for slow-growing adenoid cystic carcinoma. Most patients with this cancer type would likely seek medical attention sooner due to symptoms or visible changes, making this an exceptional case rather than a typical presentation.

The relationship between the breast cancer and the patient's stroke remains uncertain. While the stroke occurred in the context of severe anemia and possible hypercoagulable states associated with cancer, a direct causal relationship cannot be established from this case alone.

The treatment approach combining radiation therapy with concurrent cisplatin chemotherapy for adenoid cystic carcinoma of the breast is based on limited evidence, as this rare cancer type hasn't been studied in large clinical trials. Treatment decisions were made by extrapolating from experience with adenoid cystic carcinoma in more common locations like the head and neck.

Long-term outcomes for this specific treatment approach in breast adenoid cystic carcinoma remain unknown due to the rarity of the condition and the advanced stage at presentation in this case.

Recommendations for Patients

Based on this case, several important recommendations emerge for patients:

1. Seek prompt medical evaluation for any new breast abnormality or change in existing breast tissue, regardless of how slow-growing or asymptomatic it may seem
2. Maintain regular medical care even during busy life periods, as early detection of health issues significantly improves treatment options and outcomes
3. Discuss barriers to care openly with healthcare providers, who can often help address practical, financial, or psychological obstacles to receiving needed medical attention
4. Request explanations of any diagnosed breast conditions, including whether rare subtypes might require specialized treatment approaches
5. Consider genetic counseling if you have a family history of breast cancer, as this may influence screening recommendations

For patients diagnosed with rare cancer types like adenoid cystic carcinoma, seeking care at centers with multidisciplinary expertise in both breast cancer and rare tumor types may provide access to the most current treatment approaches and clinical trials.

This case powerfully demonstrates that even extremely slow-growing breast changes can eventually cause serious health complications, emphasizing the importance of regular breast awareness and timely medical evaluation of any concerning changes.

Source Information

Original Article Title: Case 26-2024: A 59-Year-Old Woman with Aphasia, Anemia, and a Breast Mass

Authors: Seth A. Wander, M.D., Ph.D., Janice N. Thai, M.D., Lori J. Wirth, M.D., Daniel E. Soto, M.D., Rebecca M. Kwait, M.D., and Bayan A. Alzumaili, M.D.

Publication: The New England Journal of Medicine, August 22/29, 2024, Volume 391, Pages 747-757

DOI: 10.1056/NEJMcpc2402489

This patient-friendly article is based on peer-reviewed research from The New England Journal of Medicine. It maintains all original medical information, data, and clinical findings while making them accessible to educated patients.