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Uncommon Presentations of Cancer Patients

CASE 1. Metastatic Breast Cancer Presenting With Panhypopituitarism

Departments of Medicine-Division of Endocrinology, Pathology and Radiology, University of Saskatchewan; and the Department of Medical Oncology, Saskatoon Cancer Center, Saskatoon, Saskatchewan, Canada.

A 60-year-old white female was referred to the endocrinology clinic with a 6-month history of unintentional weight loss, vomiting, and fatigue. Her past medical history was significant for stage III estrogen/progesterone receptor–negative infiltrating ductal carcinoma of the breast treated 12 years ago with modified radical mastectomy and adjuvant chemotherapy with cyclophosphamide, fluorouracil, and methotrexate (CMF). Her disease had been in remission until the above presentation. Physical examination was remarkable for a blood pressure of 110/80 mmHg without an orthostatic change and a pulse of 54/min. Extraocular movements and visual fields were intact and there was no organomegaly or lymphadenopathy. Laboratory investigations were consistent with the diagnosis of panhypopituitarism. Magnetic resonance imaging of the brain demonstrated a 9.5 mm x 2.7 cm x 3.3 cm nonenhancing cystic-necrotic mass in the anterior aspect of the pituitary without extrasellar extension (Figs 1A and B, arrows). Bone scan demonstrated foci of increased activity at the level T6, T11, and L2, and the computed tomography scan showed multiple spiculated mass lesions in the right apex and middle lobe and left lower lobe of the lungs, as well as a lytic lesion at T6 and in the right sixth rib. The patient had a biopsy of the right upper lobe lung nodule followed by transphenoidal hypophysectomy. The pathology from both the lesions revealed moderately differentiated adenocarcinoma; the cells were estrogen-receptor–and progesterone-receptor–negative and strongly positive for ErbB-2 by immunohistochemistry and were similar in histology (Fig 2A, B, and C) and immunohistochemical profile to the primary breast carcinoma resected 12 years ago (Fig 2D, E, and F).

View larger version (85K): [in this window] [in a new window]   Fig 1. Magnetic resonance imaging of the brain demonstrating a nonenhancing cystic-necrotic mass.

View larger version (81K): [in this window] [in a new window]   Fig 2. Immunohistochemical profile of the (A) breast, (B) lung, and (C) pituitary; and previous immunohistochemical profile from 12 years ago of (D) breast, (E) lung, and (F) pituitary.

This patient had several poor prognostic characteristics at initial presentation: premenopausal status, stage III disease, and the now determined ErbB-2 overexpression by immunohistochemistry. Studies have shown that DNA amplification or protein overexpression of this oncogene correlates with a worse prognosis.⁴ Retrospective analyses by several groups have addressed the predictive value of ErbB-2 on different chemotherapeutic regimens and have suggested that anthracycline-based chemotherapies may be superior to CMF,^5-8 more so in cases where topoisomerase-II is overexpressed.⁸ Thus, the 12-year disease-free survival of this patient with several poor prognostic indicators, treated with adjuvant CMF—a regimen that would be considered suboptimal today—is noteworthy. This can be partly explained by a recent retrospective study where patients who overexpressed ErbB-2 had a poor outcome overall, while those who had received CMF fared better than those on observation alone.⁹ Other studies have shown in a small group of patients that p21^Cip1 overexpression concomitantly with ErbB-2 overexpression was associated with resistance to CMF.¹⁰ On the other hand, those who had ErbB-2 overexpression alone without p21^Cip1 overexpression derived benefit from CMF. This case illustrates that pituitary metastases are an uncommon but important cause of panhypopituitarism and may be the initial manifestation of widely metastatic recurrent cancer. The prolonged disease-free survival in the patient, despite initial poor prognostic markers, also suggests that prognostics as well as prediction of resistance or sensitivity to chemotherapy based on single molecular markers is relative and not absolute.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

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