Adenoid cystic carcinoma of the breast with late recurrence and high-grade transformation

Case presentation

A woman in her 60s presented with a left chest wall lump for 1 year and pain of 2-week duration. Twelve years ago, she had a lump in the upper outer quadrant of her left breast and underwent a lumpectomy at an outside hospital. It was a T1 tumour and histology was reported as AdCC of the breast with positive margins. Hence, she came to our hospital for further management. A slide review at our institute confirmed the diagnosis of AdCC; however, blocks were not available to perform immunohistochemistry (IHC). The patient opted for a mastectomy and eventually underwent a mastectomy with axillary dissection. Histopathology of the mastectomy specimen showed no residual tumour. She was started on tamoxifen empirically for 5 years, per our policy for cases with unknown receptor status. She was on regular follow-up until 4 years ago and was lost to follow-up thereafter.

She had paroxysmal supraventricular tachycardia for the last 15 years and dyslipidaemia for the last 2 years. No other comorbidities or family history of malignancy was present.

Examination showed a 5×5 cm firm-to-hard lump with irregular margins and reddened skin confined to the lateral end of the previous surgical scar (figure 1). There was associated local rise of temperature and tenderness. Further ultrasonography and guided core biopsy of the lesion were also performed.

Investigations

A mammogram of the right breast showed heterogeneously dense breast parenchyma. There were no suspicious masses, architectural distortion or calcification in the right breast as confirmed on tomosynthesis sequences.

Left chest wall ultrasound revealed an irregular hypoechoic solid mass with irregular margins measuring 3.7×3.1×4 cm. Another smaller adjacent lesion was also noted measuring 2.1×1.4×3 cm. The masses had heterogeneous echotexture with intralesional vascularity and posterior enhancement. Radiologically, the masses were reported as Breast Imaging Reporting And Data System- BIRADS 4c. Possibility of recurrent AdCC or angiosarcoma was considered on radiology.

Histopathological examination of the specimen obtained by core biopsy showed a poorly differentiated neoplasm where cells were arranged in sheets with extensive areas of necrosis. The cells had scant cytoplasm with ovoid hyperchromatic nuclei. No cribriform areas suggestive of AdCC were seen. Possibility of small cell carcinoma was considered.

IHC for cytokeratin showed focal positivity, while IHC for CD34, CD31, synaptophysin and LCA was negative, ruling out angiosarcoma, lymphoma and small cell carcinoma. Even though morphology was not suggestive of AdCC, IHC for CD117 and p63 was performed given the previous diagnosis. CD117 turned out to be positive while myoepithelial marker p63 was negative. Possibility of AdCC recurrence was considered in view of CD117 positivity; however, the present case did not show diffuse cytokeratin positivity or highlight myoepithelial cells on p63, unlike a typical case of AdCC (figure 2).

Positron emission tomography-CT was then performed, and it showed thickening in chest wall (figure 3). Because of absent distant metastasis, we proceeded with wide local excision of the lesion. Surgical resection involved excision of the lump along with the underlying serratus anterior fibres over which the tumour was resting.

On gross examination of the excised sample, two distinct lesions were identified abutting each other (figure 4). One of the lesions was soft to firm in consistency, measuring 4.5×4×4 cm (lesion 1) and the other lesion was firm measuring 3×2.5×2 cm (lesion 2). On microscopy, sections studied from two lesions showed different morphological patterns. Lesion 1 showed neoplastic cells arranged in sheets with extensive necrosis and brisk mitosis. The cells had scant cytoplasm and ovoid vesicular nuclei with few showing conspicuous nucleoli. Solid-basaloid morphology was not seen. Lesion 2 revealed neoplastic cells arranged in lobules and nests separated by fibrous septae. Within the nests, cells showed cribriform and solid pattern. Cells had round-to-ovoid vesicular nuclei with prominent nucleoli and eosinophilic cytoplasm.

Eosinophilic basement membrane-like material was noted in luminal spaces. Areas of necrosis and frequent mitosis were also noted (figure 5). The lesions showed abrupt transition between each other (figure 6). IHC on lesion 2 (with classic AdCC morphology) showed CD117 positivity in luminal cells, p63 positivity in myoepithelial cells and diffuse cytokeratin positivity. IHC for oestrogen receptor, HER2/neu, synaptophysin and CD56 was negative. Ki67 was around 15%–20%. IHC in lesion 1 (with poorly differentiated morphology) showed focal CD117 staining with negative p63 staining. Cytokeratin and synaptophysin positivity were noted in occasional cells. Oestrogen receptor, HER2/neu and CD56 were negative with Ki67 of 70%–80%. The cribriform areas in lesion 2 raise the differential of an invasive cribriform carcinoma (ICC). However, CD117 positivity and oestrogen receptor negativity with positive p63 excluded ICC. Considering the morphological and IHC findings, we had areas of classic AdCC and distinct areas of poorly differentiated carcinoma leading to the diagnosis of AdCC of the breast with high-grade transformation. Margins of excision were free of tumour.

Treatment

Her case was discussed in multidisciplinary tumour board. Because of the long disease-free interval, absence of distant metastasis and the patient’s reluctance to undergo chemotherapy, it was decided to withhold chemotherapy. However, given the size and recurrent nature, local RT was offered. She underwent adjuvant RT with 50 Gy/25# over 5 weeks.

Outcome and follow-up

She tolerated the treatment well and during a follow-up CT scan after 1 year, she was detected to have local recurrence and distant metastatic nodules in both lungs. However, she decided to continue treatment elsewhere.