Metachronous or synchronous male breast and prostate cancers a duality to lookout for.

Case 1

A 64 year old black male, retired forensic pathology auditor, was referred to urology clinic at CHBAH from medical oncology at the end of June 2018 with a prostate specific antigen (PSA) of 43.82 ng/dL. His hospital attendance had begun in October 2016 when he presented to the breast unit with a 2 years history of a painless progressively enlarging left breast lump with further investigations revealing carcinoma of the left breast. He was diabetic, hypertensive on treatment, and HIV negative. There was no known family history of breast, prostate or any other cancers. There was no history of undescended testes, testicular injury or mumps orchitis. A left modified radical mastectomy was performed in April 2017. He was previously a smoker, smoking 6 cigarettes per day for 40 years (12 pack-year), and quit in May 2017.

On physical examination, performed in June 2018, scars from left mastectomy and axillary lymph nodes dissection were noted. He had a normal right breast with no palpable lumps. Digital rectal examination revealed an approximately 30 g firm prostate with a nodule on the left lobe. The rest of the examination was unremarkable.

Investigations and results

Mammography (October 2016). Mammograms showed the left breast was Breast Imaging Reporting and Data System (BIRADS) category 6 and BIRADS category 1 for the right breast.

Core biopsy of the left breast (October 2016). Pathological diagnosis: An invasive carcinoma of no special type.

Immunohistochemistry: Estrogen receptors: Strong positivity in 67–100% of cells.

Progesterone receptors: Strong positivity in 34–66% of cells. HER2neu: Score 1+ Negative. Ki-67: 20%

Left breast and axillary dissection histopathology assessment (April 2017). Pathological diagnosis: Infiltrating duct carcinoma. On macroscopic examination the left breast nipple and skin were unremarkable. On section a tumour was noted in the lower outer and inner quadrants. It measured 40mm in maximal diameter. Microscopically, the tumour comprised infiltrating epithelioid cells in a nested growth pattern, with some tubule formation. There was marked nuclear pleomorphism, and eight mitotic figures were noted in ten high power fields. The modified Bloom and Richardson classification was Grade 2. Five lymph nodes were identified, and all of these contained tumour metastases.

Immunohistochemical stains were positive for estrogen receptors, negative for progesterone receptors, and equivocal for HER2. FISH testing was negative for HER2 amplification. Ki67 staining showed a proliferation index of 20% (Figure 1). The PSA immunochemistry staining was negative confirming primary breast carcinoma.

Figure 1. Breast carcinoma showing an adenocarcinoma with marked nuclear pleomorphism.

(H&E stain, X400 magnification).

Bloods tests.

-Prostate specific antigen: 43.82ng/dL (normal range=0–4.5)

-Lactate dehydrogenase: 254 U/L (normal range=48–115)

-Calcium: 2.63 mmol/L (normal range=2.15–2.50)

-Alkaline phosphatase (ALP): 49 U/L (normal range=53–128)

Prostate biopsy. Microscopic examination of the prostate core biopsies demonstrated an invasive prostatic adenocarcinoma. The tumour comprised predominately infiltrative, poorly formed, fused glands, and a minor component of more well differentiated glandular areas that splayed muscle fibres. The poorly formed fused glands were compatible with a Gleason pattern of 4 and the well-formed glands were compatible with a Gleason pattern of 3 (Gleason score = 7; WHO grade group 3). The tumour cells had large nuclei, conspicuous nucleoli and abundant pale eosinophilic cytoplasm (Figure 2). The immunohistochemical profile of the tumour (CK 7 and CK20 negative; PSA monoclonal positive) confirmed primary prostatic origin.

Figure 2. Prostatic adenocarcinoma.

(H&E stain, X400 magnification).

Computerised tomography (CT) scan of the brain, chest and abdomen. Global cerebral involutional changes, postsurgical changes in the left chest wall and axilla, and sclerotic lesions at L3 and right iliac bone were found on the CT scans.

Bone scan. Active pathology at L3 and right iliac bone were found on Bone scan.

Management

Initially assessed as T2N0M0 in October 2016, he was put on tamoxifen 20 mg per os daily. 6 months later (April 2017) in view of disease progression to T4bN1Mx, a left mastectomy and left axillary lymph nodes dissection was done. Tamoxifen was replaced by anastrozole 1 mg daily and He was then referred for chemo-radiation. He received 4 cycles of chemotherapy AC-T (Adriamycin, cyclophosphamide and taxol) completed in January 2018. A second primary cancer, a prostatic adenocarcinoma was diagnosed in July 2018, almost 2 years after the initial one, for which he is currently on Goserelin 10.8 mg subcutaneously every 3 months. He has so far received 2 injections (July and October of 2018) and will follow up in 3 months for the next injection, and PSA/testosterone monitoring will be done at 6 months as per the hospital policies (funds restrictions). He is unlikely to be given radiation therapy for curative intent as the disease was found to be metastatic.

Case 2

A 68 year old black male, retired teacher, was referred to urology clinic at CHBAH in May 2018 from medical oncology with a PSA of 113 ng/dL. He first presented in December 2016 to CHBAH breast unit with a 1 year history of a painless right breast lump with further investigations revealing carcinoma of the right breast. He reported that his father died of cancer, but does not know which cancer it was. He had no medical history, was HIV negative, and had no history of undescended testes, mumps orchitis or testicular injury. He was a heavy smoker who smoked 20 cigarettes per day for 40 years (40 pack-year) and quit in July 2016. Right mastectomy and axillary lymph nodes dissection was performed in April 2017.

On physical examination, scars from right mastectomy and axillary lymph nodes dissection were observed. He had a normal left breast with no palpable lumps. Digital rectal examination revealed an approximately 40 g hard nodular prostate. The rest of the examination was unremarkable.

Investigations and results

Mammography (December 2016). Mammograms showed the left breast was BIRADS category 1 and BIRADS category 5 for the right breast.

Core biopsy of the right breast (December 2016). Pathological diagnosis: Infiltrating duct carcinoma displaying cribriform features.

Immunohistochemistry: Estrogen receptor positive; strong 3+ intensity staining in >91% of tumour cells. Progesterone Receptor positive; strong 3+ intensity staining in 70% of tumour cells. HER2 negative score 1+ in approximately 10% of tumour cells. Ki-67 the tumour proliferation index approaches 30%.

The right breast histopathological assessment. Histopathological examination showed an infiltrating duct carcinoma (Figure 3), with a Nottingham combined histopathological grade of 1/3 (tubules 1, pleomorphism 2 and mitoses 1). Estrogen and progesterone receptors were expressed diffusely within the tumour cells (Figure 4). Foci of low-grade cribriform ductal carcinoma in situ were also evident (Figure 5). The PSA immunochemistry staining was negative confirming primary breast carcinoma.

Figure 3. Breast infiltrating duct carcinoma (H&E stain, X200 magnification).

Figure 4. Oestrogen receptors diffusely expressed in the breast carcinoma (estrogen receptor (ER) immunohistochemistry, X200 magnification).

Figure 5. Breast cribriform ductal carcinoma in situ (DCIS) (H&E stain, X200 magnification).

Bloods tests.

-Prostate specific antigen: 113ng/dL (normal range=0–4.5)

-Lactate dehydrogenase: 289 U/L (normal range=48–115)

-Calcium: 2.56 mmol/L (normal range=2.15–2.50)

-ALP: 73 U/L (normal range=53–128)

Prostate biopsy. Biopsy results showed an invasive prostatic adenocarcinoma (Figure 6), with a modified Gleason score of 9, and grade group 5, which was infiltrating into skeletal muscle (Figure 7). The proportion of tumour infiltration was >90% within the cores. There were areas of lymphatic invasion and perineural invasion.

Figure 6. Invasive prostatic adenocarcinoma (H&E stain, X200 magnification).

Figure 7. Invasive prostatic adenocarcinoma infiltrating into skeletal muscle (H&E stain, X200 magnification).

Bone scan. No evidence of osteoblastic metastases was found.

Management

He was assessed from the beginning in December 2016 as T4bN0Mx, he was put on tamoxifen 20 mg per os daily. 4 months later (April 2017), due to disease progression on tamoxifen from T4bN0Mx to T4bN1Mx, a right mastectomy and right axillary lymph nodes dissection was done prior to referring him for chemo-radiation. He received 6 cycles of chemotherapy FAC, (Fluorouracil, Adriamycin and cyclophosphamide) completed in January 2018; he is still on tamoxifen. A second primary non metastatic cancer arising from the prostate, a prostatic adenocarcinoma, was diagnosed in May 2018, 17 months after the first primary. He is currently on Goserelin 10.8 mg subcutaneously every 3 months and has already received 2 doses. He is awaiting radiation therapy to the right chest. PSA/testosterone monitoring will be performed at 6 months as per the hospital policies (funds restrictions). Radiation oncologist will consider external beam radiotherapy at the time of radiation for right chest.