Thyroid transcription factor-1 positive primary breast cancer: a case report with review of the literature
© Klingen et al; licensee BioMed Central Ltd. 2010
Received: 28 May 2010
Accepted: 17 June 2010
Published: 17 June 2010
This case describes an infiltrating breast tumour with thyroid transcription factor-1 (TTF-1) positive staining and ductal differentiation in a 72-year-old woman. The presence of ductal carcinoma in situ with positive TTF-1 is a strong indication that this is a primary tumour and not a metastasis from lung.
On PET scan and CT follow up there were no other tumours found in this patient. We are not aware of any previously reported TTF-1 positive primary breast carcinoma with ductal differentiation.
TTF-1 is a tissue-specific transcription factor expressed in epithelial cells of the lung and the thyroid, including C-cells as well as certain areas of the brain. TTF-1 is expressed in approximately 72% of pulmonary adenocarcinomas, and may be a valuable marker for identifying the lung as the site of origin of a metastatic adenocarcinoma.
A 72-year-old gravida 1/para 1 woman presented with a palpable mass in the left breast.
Her sister died of breast cancer some years earlier. There was a past history of operated parathyroid adenoma some years ago but no previous history of any malignancy. The patient was a non- smoker and had never used hormonal drugs.
Clinical examination demonstrated a palpable tumour in her left breast in the upper inner quadrant, no fixation to skin or underlying fascia.
Mammography from upper inner quadrant of the left breast showed a dense, relatively well defined, oval shaped mass lesion with a microlobulated margin measuring 51 × 33 × 35 mm with coarse calcifications centrally in the mass and in addition finer micro calcifications antero lateral to the main tumour, malignant in appearance. The total maximal diameter including the calcifications was approximately 6 cm.
Ultrasound left breast showed an irregular solid malignant appearing tumour, corresponding to the mammographic lesion, measuring approximately 38 mm maximal diameter. No enlarged lymph nodes in the left axillae. PET scan and CT scan showed no other malignancy other than known breast tumour.
As no other origin for the tumour was found, the patient was treated with left mastectomy and sentinel lymph node mapping. The sentinel node was normal. The patient had an uncomplicated recovery and was discharged the next day following the operation.
Materials and methods
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We believe this case represents TTF-1 positive infiltrating ductal breast carcinoma, histological grade 3. The tumour was heterogeneous with small areas of basal-like and neuroendocrine differentiation.
In three large studies of primary breast carcinomas [1–3] there were 96, 51 and 35 (total 182) carcinoma cases, respectively, that were all TTF-1 negative. Only a few cases of TTF-1 primary small-cell carcinoma in breast have been reported [4, 5]. Yamamoto described two small-cell breast carcinomas with positive TTF-1 whilst Ersahin reported one case of small-cell breast carcinoma which was positive for TTF-1 and basal-like markers. In the case we report, we found no areas typical for small cell carcinoma growth, although some areas with trabecular growth gave a partial neuroendocrine impression. Because of heterogeneous growth with focally oval and spindled shaped nuclei, a metaplastic carcinoma was considered. It is difficult to rule out this alternative, but a lack of squamous or heterologous metaplasia makes this less possible.
The initial investigations of the biopsy gave suspicion of metastasis from lung cancer because of the positive TTF-1 reaction. Previous studies have shown that lung cancer, malignant melanoma and lymphoma are the three most common candidates for secondary breast tumours [6–8]. An almost round tumour could resemble a metastasis, but some high grade primary tumours can also have this shape. In our case the tumour was deep seated in the breast (6 mm from the chest wall). This correlates poorly with secondary breast tumours which are often found near to the skin [6, 8].
The presence of a positive TTF-1 reaction in the in situ component as well as in the invasive component in this case gives strong support for primary breast carcinoma. We are not aware of any previously reported TTF-1 positive ductal carcinoma in situ of non small-cell type. In order to be quite sure that this represented breast ducts and not vessels with tumour tissue or peritumoral retraction artefacts, we also investigated these areas with MA and p63. Both markers were positive for myoepithelial cells.
HER2/neu expression can be seen in both carcinomas of breast and lung . Our findings with C-erb-2 protein score 2+/3+ and SISH without gene amplification have no differential value in this case. We found weak postive reaction for PGR in the core biopsies. Positive reactions for both ER and PGR have been reported for lung cancer  and give therefore no support to either breast cancer or metastasis diagnosis.
In agreement with Ersahin et al we found a positive expression of the basal-like marker CK5/6. This was especially noticeable in the in situ component, but only scattered positive cells in the invasive component. This can possibly represent a dedifferentiation in the tumour tissue. Previous studies have considered ductal carcinoma in situ with basal- like phenotype as a possible precursor to invasive basal-like cancer [13, 14].
Our case showed high grade ductal carcinoma in situ and invasive tumour, and such tumours are more commonly basal like than low to intermediate grade lesions .
We have presented an unusual case of TTF-1 positive primary infiltrating ductal carcinoma with focal basal-like and neuroendocrine differentiation. The in situ component with positive TTF-1 is the most important indication that this represents a primary tumour. Despite the fact that TTF-1 is known as a specific marker for lung and thyroid tumours, this case shows that primary non small-cell breast carcinomas can also be positive.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
We thank Marianne Odnakk Ludahl and Henning Jørgensen (Department of Pathology, Vestfold County Hospital) for excellent technical assistance.
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