What is the appropriate immediate management for a patient with left breast and nipple pain, swollen axillary lymph nodes, flank pain, a low anion gap, and elevated mean corpuscular hemoglobin?

Immediate Management of Suspected Occult Breast Cancer with Axillary Lymphadenopathy

This patient requires urgent diagnostic workup for occult breast cancer, beginning with bilateral breast imaging (mammography and ultrasound), followed by breast MRI if initial imaging is negative, and core needle biopsy of the axillary lymph nodes to establish tissue diagnosis. 1

Initial Diagnostic Approach

Imaging Studies (Perform Immediately)

• Bilateral mammography should be obtained first to evaluate for any occult primary breast lesion, as adenocarcinoma with positive axillary nodes in a woman is highly suggestive of breast primary. 1

• Bilateral breast ultrasound must be performed in conjunction with mammography, as this combination is more sensitive for detecting occult lesions, particularly in women with dense breast tissue. 1

• Breast MRI should be performed if mammography and ultrasound are negative or indeterminate, as MRI identifies the primary breast lesion in approximately 70% of patients with biopsy-proven axillary metastases and negative conventional imaging. 1

• Axillary ultrasound should be performed to better characterize the lymphadenopathy and guide biopsy. 1

Tissue Diagnosis (Critical Next Step)

• Core needle biopsy of the axillary lymph nodes (preferred over fine needle aspiration) should be performed immediately to establish histologic diagnosis and allow for immunohistochemical analysis. 1

• Immunohistochemical staining for ER/PR and HER2 must be obtained on the biopsy specimen, as elevated ER/PR levels provide strong evidence for breast cancer diagnosis and guide subsequent treatment decisions. 1

Staging Workup for Distant Metastases

• Chest and abdominal CT should be performed to evaluate for distant metastases, particularly given the concerning flank pain which could indicate renal or retroperitoneal involvement. 1

• The flank pain warrants specific attention to rule out renal involvement or other visceral metastases that would upstage the disease. 1

Laboratory Evaluation

Address the Metabolic Abnormalities

• Low anion gap (reference range now 3-11 mmol/l with modern ion-selective electrode methods) may indicate hyperglobulinemia, which can occur with multiple myeloma or other plasma cell dyscrasias. 2

• Elevated MCH combined with low anion gap raises concern for a paraproteinemia or IgG multiple myeloma, which has been reported with anion gaps as low as 2 mmol/l. 2

• Serum protein electrophoresis and immunofixation should be obtained to rule out concurrent plasma cell dyscrasia, as the combination of low anion gap and elevated MCH is suspicious for this diagnosis. 2

• Complete metabolic panel, albumin, and total protein should be checked, as hypoalbuminemia can also cause decreased anion gap. 2

Critical Clinical Pitfalls

Do Not Delay Tissue Diagnosis

• Never proceed with empiric treatment without histologic confirmation, as the differential diagnosis includes primary breast lymphoma (which presents with breast mass and axillary adenopathy but requires entirely different treatment), inflammatory breast cancer, or metastatic disease from an occult primary. 3, 4

• Primary breast lymphoma accounts for 0.5% of breast malignancies and can present with palpable breast masses and axillary lymphadenopathy, requiring systemic chemotherapy rather than surgical resection. 3, 4

Rule Out Inflammatory Breast Cancer

• Assess for erythema occupying at least one-third of the breast, peau d'orange, or rapid onset of symptoms (less than 6 months), as these features suggest inflammatory breast cancer rather than occult primary. 5

• History of symptoms not responding to at least 1 week of antibiotics should raise suspicion for inflammatory breast cancer. 5

Avoid Premature Surgical Intervention

• Do not perform frozen section or primary axillary dissection until invasive carcinoma is confirmed on permanent histology. 1

• Excisional biopsy of axillary nodes should be avoided; core needle biopsy provides adequate tissue for diagnosis and receptor testing. 1

Treatment Algorithm Based on MRI Findings

If MRI Identifies Primary Breast Lesion (70% of cases)

• Proceed with ultrasound or MRI-guided biopsy of the breast lesion to confirm diagnosis. 1

• Treat according to the clinical stage of breast cancer based on tumor size and nodal involvement. 1

If MRI is Negative (30% of cases)

For T0, N1, M0 disease (limited axillary involvement):

• Option 1: Axillary lymph node dissection plus whole-breast irradiation with or without nodal irradiation. 1

• Option 2: Modified radical mastectomy plus axillary lymph node dissection. 1

• Systemic therapy (chemotherapy, endocrine therapy, or trastuzumab) should be administered according to recommendations for stage II or III disease based on receptor status and nodal burden. 1

For T0, N2-N3, M0 disease (extensive axillary involvement):

• Neoadjuvant chemotherapy, trastuzumab (if HER2-positive), and endocrine therapy (if hormone receptor-positive) should be considered first. 1

• Following neoadjuvant therapy, proceed with axillary lymph node dissection and mastectomy as for locally advanced disease. 1

Addressing the Metabolic Abnormalities in Context

• The low anion gap and elevated MCH are not directly related to breast cancer management but require parallel investigation for plasma cell dyscrasia or other hematologic conditions. 2

• If multiple myeloma is confirmed, this would represent a separate primary malignancy requiring concurrent hematology/oncology management, as breast cancer and multiple myeloma can coexist. 2

• The flank pain could represent either metastatic breast cancer (requiring staging CT) or renal involvement from myeloma (requiring additional workup including bone marrow biopsy if paraprotein is detected). 2