No single institution sees enough cases of MBC to achieve a series of meaningful size for histological evaluation and comparison with FBC. Those large published series that are available for analysis have been derived from national studies [1–3]. In 1948, Norris and Taylor from the US Armed Forces Institute of Pathology (AFIP), reviewed the specimens from 113 cases of MBC which comprised 2.4% of the total pool of breast cancer material.

They reported that the gross features of MBC were similar to FBC, with most being firm gritty and containing yellowish and haemorrhagically streaked foci. Because of the absence of surrounding breast tissue most were more evident than FBC. Microscopically, 8 (7%) were ductal carcinoma in situ (DCIS). The predominant histological type was ductal carcinoma of no special type, diagnosed in 92 (81%). Results are summarised in Table 5.1, which shows that 9 (10%) were of papillary type. Although Paget’s cells were seen in the epidermis of 12 (11%), no clinical cases of Paget’s disease had been diagnosed.

Visfeldt amassed 265 Danish cases of MBC and was able to histologically type and grade 187 of them. The predominant type was invasive ductal carcinoma and in this series, no cases of invasive lobular cancer were seen. It was possible to grade 150 of the invasive ductal carcinoma of which 44 (29%) were grade I, 81 (54%) grade II and 25 (17%) grade III. Special types included medullary 4, papillary 5, cribriform 5, and Paget’s disease 3.

Using data from the Swedish Cancer Registry acquired between 1958 and 1967 Hultborn et al. reported 190 cases of male breast cancer and the specimens underwent central histopathological review [4]. All of the cancers were of ductal type but four were DCIS. There were no pure mucinous cancers but three showed partial mucinous change and another three showed medullary change. The Sloane-Kettering Memorial group amassed 104 MBC patients with 106 breast cancers [5]. Most were IDC but there were two medullary/tubular cancers. Donegan et al. reviewed 217 cases of MBC reported to 18 tumor registries in Wisconsin and reported that they were overwhelmingly of invasive ductal type 196/217 (90%) [6]. There were 12 DCIS, 4 invasive papillary carcinomas, 1 phyllodes tumour, 1 leiomyosarcoma and 1 inflammatory carcinoma.

Muir et al. conducted a case control study with 59 cases from the Saskatchewan Cancer Foundation collected between 1970 and 1996 [7]. The controls were stage matched FBC cases and histological review of tumour grade was carried out together with IHC for ER, PR, HER2, p53 and Bcl2. Results are outlined in Table 5.1. Of the MBC specimens, 85% were grade III, compared with 50% of FBC but MBC were more frequently ER+ve (81% vs 69%). Most noticeably HER2 amplification was less frequent in MBC (5% versus 17%) as was overexpression of p53 (9% versus 28%).

Between 1979 and 1999, Ben Dhiab et al. collected 123 Tunisian MBC cases, summarised in [8] In 2006 a larger series of 759 archival cases from the AFIP was reported by Burga et al. The majority, 85% were invasive ductal carcinoma (IDC) and 26 were a mixture of IDC and mucinous with 21 being pure mucinous cancers. Carcinoma associated with Paget’s disease of the nipple was reported in 34 cases (4%). There were 19 cases where the malignancy was a secondary within the breast with the commonest primary site being melanoma. Pure invasive lobular carcinoma was diagnosed in only three cases with a mixed ductal/lobular pattern in another 3.

A large French cohort of 489 cases was reported by Cutuli et al. in 2010 [9]. There were 462 (95%) which were IDC and of these 22% were grade I, 51% grade II and 20% grade III. Bourhafour et al. from the National Institute of Oncology, Rabat Morocco acquired data on 127 MBC seen between 1985 and 2007 [10]. IDC comprised 96% of the cases and 82% of these were grade II/III. There were 2 with Paget’s disease and 2 ILC. Aggarwal et al. reported 51 cases of MBC from the Veterans Affairs Medical Center and of these 90% had IDC with 5 DCIS and one sarcoma [11]. A series of 42 Nigerian MBC cases reported that 15 were grade I, 7 grade II and 20 grade III [12]. There were 37 (88%) IDC, 1 papillary, 2 ILC and 2 mixed IDC/ILC (Table 5.2).

Like Gaul, intracystic papillary lesions may be divided into three parts: benign, non-invasive (DCIS) and invasive. All these have been described in males as rare lesions but for the most part long-term follow-up has been lacking so the behaviour of these diverse intracystic abnormalities is only patchily understood.

In 1946 Moronet reported a 31 year old man with a 2 year history of intermittent bloody right nipple discharge who was treated by total mastectomy [13]. Histology showed extensive intraductal papilloma (IDP) with no evidence of malignancy. Reviewing paediatric breast lesions seen at the Toronto Hospital for Sick Children over a 40 year period, Simpson and Barson described a 7-month-old Native American boy with a lump under the right nipple of the right breast, present for 4 months [14]. The lump measured 5 cm and was excised together with the nipple and proved to be a benign papilloma. This was the youngest male case of benign IDP and subsequent reports have been summarised in Table 5.3. Volmer et al. reported a 26 year-old male who had a pituitary adenoma and gynaecomastia and presented with mass that was an IDP [15].

Detraux et al. investigated a series of 7 males with nipple discharge using galactography [16]. Of these, two men had IDPs, two had intraductal carcinoma and there was one abscess and two cases of duct ectasia. Sara et al. described a 71 year-old man who had been taking phenothiazines for more than 10 years and complained of a coffee-coloured left nipple discharge [17]. There was a 10 cm mass which on resection proved to be an IDP. An 82 year old with a 10 cm mass was reported by Martorano Navas et al. and because of cytological atypia a mastectomy was performed for this IDP [18]. Georgountzos et al. reported a 56 year-old man who gave a 2 year history of intermittent bloody discharge from the left nipple [19]. He was taking no medications and aspiration yielded atypical cells so excision was performed which confirmed IDP.

Shim et al. reported a 22 year-old with a mass fixed to the chest wall which was a complex cystic lesion on ultrasound and proved to be an IDP after excision [20]. A second case of IDP after long-term phenothiazine to a 57 year-old schizophrenic was described by Yamamoto et al. [21]. Durkin et al. reported a 14 year-old boy with an IDP which had caused unilateral breast enlargement [22]. The case presented by De Vries et al. was a 29 year-old male with a 1 cm lump beneath the left nipple which was lobular and solid on ultrasound [23]. These cases indicate that IDP can occur at any age in the male and usually presents as a lump, sometimes with an associated blood stained discharge. The treatment has been surgical to date but it is possible that smaller lesions could be extirpated via a ductoscope.

These rare lesions may be indistinguishable clinically, radiologically and cytologically from IDP. Histologically the papillary lesion contains round/polyhedral carcinoma cells with mild atypia, rare mitoses and no stromal invasion. As Table 5.4 shows the cases occur predominantly in the sixth and seventh decades, usually presenting as a painless breast lump [21, 24–45].

Imoto and Hasebe reported a 62 year-old with intracystic papillary carcinoma together with four cases from the Japanese literature [29]. The first reported pre-operative diagnosis by ultrasound-guided core biopsy came from Pacelli et al. [32] The predominant surgical intervention has been either modified radical (MRM) or total mastectomy (TM). There are no 5-year follow-up data but the early outcomes indicate a good prognosis for males with intracystic papillary carcinoma in the absence of adjuvant radiotherapy or systemic therapy.

Invasive papillary carcinoma is a rare but sometimes aggressive variant of MBC. It is characterised by delicate pseudopapillary fronds without a fibrovascular core together with tubuloalveolar structures floating freely within clear lacunae. In 1958 Benet described a 64 year-old schoolmaster who gave a 2 year history of a gradually enlarging right breast lump treated in Mauritius by mastectomy [46]. This was reported as an intraductal papilloma with probable malignant change. He remained well without recurrence 4 years later (Table 5.5). Blaumeiser et al. reported a 77 year-old male with a breast lump [47]. As part of the work-up they carried out breast MRI. Because of the patient’s dyspnoea MRI was modified using T1 weighted spin echo (SE) sequence which outlined an irregular tumour mass hypodense on T2 weighted sequence. TI SE after gadolinium showed inhomogeneous enhancement of signal. These findings did not lead to a definite pre-operative diagnosis. He was treated by modified radical mastectomy with 0/9 nodes involved.

Zeppa et al. studied the cytology from a 3 cm breast lump in a 55 year-old male [48]. Smears were hypercellular with isolated cells and papillary structures. Cells showed tall and well-defined cytoplasm. DNA histogram showed aneuploidy and histology confirmed papillary carcinoma with lymphatic invasion extending to the chest wall. Erhan et al. reported a 66 year-old man with a 1.5 cm grade III invasive micropapillary carcinoma, who had lung and adrenal metastases at the time of diagnosis. These micropapillary invasive cancers are often aggressive and associated with early lymphovascular invasion. Khalbuss et al. described a 67 year-old with known prostate cancer who complained of a retroareolar painless mass [49]. Fine needle aspiration cytology yielded a cellular specimen with papillary clusters. IHC of the cell block was positive for mammaglobin and negative for PSA. Wide excision confirmed a grade II infiltrating papillary carcinoma with associated DCIS. Pant et al. made a pre-operative cytological diagnosis of papillary carcinoma which proved histologically to be a moderately differentiated invasive papillary carcinoma [50]. Arora et al. reported two cases of invasive papillary carcinoma, both treated by mastectomy and recurrence-free after a year [51].

Loss of heterozygosity (LOH) on 16q has been reported in infiltrating papillary FBC but Yoshida et al. reported no LOH in their 64 year old male patient [52]. Petinato et al. reported a series of 62 cases of micropapillary invasive cancer of whom one was male [53]. Of the 41 patients with follow-up data, 71% developed local relapse after an average of 30 months and 49% had died of metastatic disease indicating the poor prognosis of this particular cancer. After a core biopsy had shown invasive cancer Tsushimi et al. performed a mastectomy and axillary clearance for a node negative invasive papillary carcinoma [54]. Vagholkar also carried out a modified radical mastectomy for a 55 year-old male with invasive papillary carcinoma who, like the others in this series, proved to be node negative [55].

Because of the absence of lobular differentiation in normal males, invasive lobular carcinoma is a rare form of MBC comprising <2% of cases. It is characterised microscopically as sheets of small rounded cells often displaying “Indian filing”, that is, single file cellular infiltration. Usually there is pure ILC but sometimes alveolar type is seen and less frequently pleomorphic, signet cell histiocytic or apocrine changes are seen. With immunohistochemical (IHC) staining the cells are e- cadherin negative.

Originally called small cell carcinoma this was originally described by Norris & Taylor in 1969 [1]. Since then there has been a steady dribble of cases and these are summarised in Table 5.2. Two cases of ILC out of a series of 16 MBC cases seen at the Medical College of Virginia were described by Giffler and Kay in 1976 [58]. In 1986 Sanchez et al. reported a case of invasive lobular carcinoma (ILC) of the breast in a 61 year old white phenotypic male [59]. After the diagnosis had been made the patient underwent endocrine and karyotypic analyses. Serum testosterone was within the normal range but there was elevation of FSH and LH with reduced urinary 17-ketosteroids. The patient’s leukocytes were subjected to cytogenetic analysis with 94% of the cells being 47XXY (Klinefelter’s).

Within a series of 4 cases of MBC, Chandrasekaran et al. reported that two were of Klinefelter’s genotype and both of them had ILC [60]. Briest et al. treated a 52-year-old man with ILC who was subsequently shown to be carrying a pathological mutation of BRCA2 [61]. Mariolis-Sapsakos et al. reported a case of ILC in a 74 year old man with two children and a duplication of the heterochromatic region of chromosome 1 [62]. They reviewed the available literature and found that there were 18 previous cases, of whom 9 (50%) had cytogenetic analyses performed. Klinefelter’s, 47XXY was confirmed in 3 (33%).

Moten et al. used the Surveillance, Epidemiology, and End Results database 1988-2008 to identify patients with ILC [63]. Of the 133,339 cases 171 (0.1%) were male who were more likely than women to have grade III cancers (26% versus 15%. Additionally, men were more likely to present with stage IV disease (9% versus 4%. Spencer and Shutter described the first case of a 58 year-old man who presented with bilateral ILC and increase in girth as result of carcinomatosis [64].

Maly et al. reported a 44 year-old Ashkenazi father of 3 who presented with a left breast lump which on biopsy proved to be a pleomorphic invasive lobular carcinoma (PILC) [65]. On microscopy these aggressive cancers contain hyperchromatic, pleomorphic cells with high nuclear/cytoplasmic ratio. Nucleoli are prominent and the cytoplasm is moderately eosinophilic with cells arrayed in dyscohesive sheets which lack e-cadherin expression. Cells often display signet-ring formation together with intracytoplasmic neo-lumina with targetoid appearance.

Since that first description of PILC in MBC there have been further sightings. Rohini et al. described a 55-year-old male with a left breast lump present for 5 months [66]. There were no known risk factors such as oestrogen or drug use. Despite having a reputation for being an aggressive lesion all three cases were alive without recurrence at the time of reporting. Cases are summarised in Table 5.6 [1, 56, 58, 60, 65, 67–84].

Secretory carcinoma is characterised by two particular histological features: presence of extensive intracellular and extracellular secretions and within the cells, granular eosinophilic cytoplasm. This rare cancer was first described by McDivitt & Stewart as juvenile carcinoma because of the young age at presentation [85]. It was subsequently dubbed secretory breast cancer (SBC) by Tavassoli et al. who reported 19 cases of whom one was a 9 year-old boy [86]. They found two cell types, A and B. The former were slightly granular with extensive secretions within the malignant cells and also in the extracellular lumens. Type B cells were round/polygonal shaped with granular or vacuolated cytoplasm. Invariably there was a mixture of the two cell types. The tumour was treated by local excision and the patient remained disease-free 21 months after surgery.

It is likely that the first case reported was a 6-year old boy with a left breast lump [87]. The biopsy was sent to several notable pathologists including Dr. Stewart and all were agreed that this was an adenocarcinoma although Dr. Stewart commented that he had never seen a cancer in so young an individual. Reviewing 9 breast tumours in infants and children seen at the Hospital for Sick Children, Toronto, over a 40-year period Simpson & Barson reported a 5 year-old boy with a secretory carcinoma. This was treated by excision and there had been no recurrence at the time of publication [88].

The full list of 25 reported cases of SBC is summarised in Table 5.7 [86–108]. Karl et al. reported a 3-year-old boy with a node positive SBC, treated by radical mastectomy, who survived without recurrence for an unspecified duration [91]. Unfortunately because of an urge to publish details of these rare cases very few studies reported a follow-up of ≥5 years. The exception was the report of Krausz et al. from the Hammersmith Hospital which included four females and one male [94]. Recurrence occurred in four cases after 3, 5, and 8 in females and 20 years in the MBC case. The latter patient presented in 1961 with a longstanding lump and was treated by total mastectomy and axillary irradiation. In 1981, after developing arm lymphoedema he was found to have axillary nodal, scalp and hepatic metastases which did not respond to chemotherapy.