A woman in her thirties with breast cancer and bilateral goitre

A woman in her late thirties was electively hospitalised on suspicion of a locally advanced carcinoma of the right breast. Her medical history showed that she had had type 1 diabetes mellitus since she was 11 and had been found to have an extra, non-functioning renal system. A couple of years previously, ultrasound and CT throat had been used at a local hospital to examine her for bilateral goitre. The conclusion of these tests was colloid nodular goitre with no suspicion of malignancy. There is no information as to whether cytology tests were carried out. The patient had two children. Several of the patient’s maternal aunts and uncles had died of cancer.

Suspicion of locally advanced carcinoma of the right breast arose following mammography conducted by a private X-ray institute. The patient suffered from breast tenderness and had requested the examination. The examination of breasts and axillae revealed possible malignant changes in the right breast, possible lymph node metastasis in the right axilla and non-specific changes in the left breast. The radiological diagnosis was regarded as certain, and the patient was referred directly for hospitalisation. Biopsies taken in connection with hospitalisation revealed ductal mammary carcinoma in the right breast and lymph node metastasis in the right axilla.

A cytological sample from a radiologically benign-seeming lesion in the left mamma revealed papillary cell groups without atypical signs. No biopsy was taken from this lesion. A further X-ray examination of the thyroid yielded an image consistent with nodular colloid goitre, but cytological samples contained too little material and were non-diagnostic. The patient received pre-operative chemotherapy and lost her hair. It proved difficult to find a wig that was large enough for her head. Seven months after the start of chemotherapy, ablatio of the right breast was performed with subsequent post-operative radiotherapy.

Because of pressure symptoms in the throat and respiratory discomfort, a further radiological examination was made of the thyroid, and cytological samples obtained, but these too failed to provide sufficient material for diagnosis. The patient's left thyroid lobe was removed the year after she was treated for cancer of the right breast, although there was no preoperative cytological diagnosis. A macroscopic examination of the left thyroid lobe revealed multiple tightly packed nodules (Fig. 1). A histological examination revealed an unusual image with tightly packed follicular adenomas and adenomatous colloid nodules (Fig. 2). The changes are consistent with findings in the literature described as characteristic of Cowden’s syndrome (CS), which is a dominant hereditary condition characterised by multiple benign and malignant neoplasms and hamartomas. The histology report indicated that the image could suggest Cowden’s syndrome, and the patient was referred for genetic testing. The same year as the left thyroid lobe was removed, a cavernous haemangioma was also removed from the skin of the left thigh.

The phosphatase and tensin homologue gene, PTEN, is a tumour suppressor gene and plays a central part in controlling cell proliferation, differentiation and apoptosis (1). Mutation of the gene contributes to increased cellular proliferation, and somatic mutations of the PTEN gene are associated with a number of different types of cancer (2, 3). PTEN hamartoma tumour syndromes (PHTS) are rare, hereditary conditions and due to germline mutations in the PTEN gene. The condition includes Cowden's syndrome, Bannayan-Riley-Ruvalcaba syndrome (BRRS), Proteus syndrome and Proteus-like syndromes and autism spectrum disorders associated with macrocephaly (4).

About two years after she had been found to have mammary carcinoma, the patient arrived with her mother for genetic counselling. Her mother related that the patient had been sick a great deal as a child. She was found to have nasal polyps during her childhood. She had a tonsillectomy and appendectomy, and was found to have diabetes mellitus. Her mother related that the patient had always had a large head, which was noticed for the first time when she was a newborn baby. The patient was monitored for a year on this account. The assessment during her childhood ruled out hydrocephalus as the cause of her large head circumference. The large circumference could be the reason why it was difficult to find a wig large enough for the patient’s head in connection with her chemotherapy.

It emerged that the patient had been referred for genetic evaluation 12 – 13 years previously because of a history of breast and ovarian cancer in her mother’s family. At that time the patient did not have cancer. Nor did her mother have cancer, and there was no indication for further genetic evaluation and testing. At that time, genetic testing options were relatively limited, and testing for PTEN gene mutation was not offered. The patient's father died when he was in his mid-fifties, but not of cancer.

In connection with the genetic counselling for which she was referred on account of suspected Cowden’s syndrome, skin manifestations were detected that were characteristic of PTEN mutation (papillomas and trichilemmomas). The genetic test revealed a mutation of the PTEN gene. This, coupled with the clinical picture, fitted Cowden's syndrome.

Further genetic tests were conducted on the family. The patient’s mother was tested, but she did not have a genetic defect in the PTEN gene. Because of the maternal family history of breast and ovarian cancer, an analysis was performed of her BRCA1 and BRCA2 genes, which did not reveal a mutation. The possibility that the PTEN genetic defect stemmed from the patient’s deceased father cannot be dismissed. Alternatively, it may have arisen de novo in the patient.

After being assessed by a medical geneticist, the patient was referred for examination of the remaining left breast. Two years had passed since carcinoma was diagnosed in the right breast. An MRI scan of the left breast revealed a suspected malignant lesion. A biopsy revealed infiltrating ductal carcinoma, and the patient underwent ablatio of the left breast. In parallel with the detection of the mammary carcinoma of the left breast, a further ultrasound of the right thyroid lobe found multiple nodules, some of them large and indeterminate. Cytological sampling from a small nodule in the right thyroid lobe revealed a cell picture consistent with a colloidal nodule, while the material from a large nodule was not diagnostic. In view of increasing pressure symptoms and throat discomfort, the remaining right thyroid lobe was removed a few months after ablatio of the left breast. The histology of the right thyroid lobe revealed a 90 mm follicular adenoma and several adenomatous colloidal nodules, consistent with findings in the left thyroid lobe.

MRI and CT scans of the patient later the same year showed changes consistent with skeletal metastases in the spinal column and pelvis and multiple small changes consistent with pulmonary metastases. Clinically, these changes were interpreted as spreading from the patient’s mammary carcinoma, and chemotherapy was started. The patient is alive, and receiving regular follow-up and treatment.