A previously healthy 31-year-old woman was referred to our cancer center following a recent discovery of a left breast lump. Her family history included an aunt who had died from ovarian cancer. Clinical examination revealed a nodular lesion located at the exterior upper quadrant of the left breast with no signs of inflammation or lymph node involvement. Routine hematological and biochemical investigations were unremarkable. Ultrasound study and mammography both showed a mass measuring 37 mm, classified as ACR4 (8). Biopsy of the mass revealed mammary parenchyma diffusely infiltrated by a moderately differentiated adenocarcinoma composed of variable sized glands in a discreetly fibrous stroma. These glands were lined by tall columnar epithelial cells displaying abundant eosinophilic cytoplasm, moderate atypia and rare mitoses. Some cells had intra-cytoplasmic mucin vacuoles (Figures 1 and 2).
An extensive immunohistochemical panel was performed and showed positivity with epithelial markers: CK7+ (strong and diffuse); CK20+ and CEA + (weak and focal).
Other stains such as: Oestrogen Receptor (ER), Progesterone Receptor (PR), HER2, Mammaglobin, GATA3, TTF1, P40, P63, CD117 and PAX8 were all negative (Figure 3).
The initial diagnosis proposed was a triple negative grade 1 invasive ductal carcinoma according to the modified Scarff-Bloom-Richardson classification system (9).
Consequent imaging by Computed Tomography revealed a well-defined cystic anterior mediastinal mass with central necrosis, measuring about 10 cm and compressing adjacent anatomical structures. It also showed atelectasis, pulmonary and pleural thickening, multiple pulmonary nodules as well as regional lymphadenopathy.
Scintigraphy revealed multiple bone foci at the levels of L3, S1 and S2 and at the level of the 6th intercostal rib.
A Positron-emission tomography scan found two suspicious hypermetabolic lesions in the left breast, multiple positive foci at the level of the left pleura, left lung, left adrenal gland and multiple bone sites associated with mediastinal lymphadenopathy. No anomalies in the gastrointestinal tract were found.
Subsequent biopsy of the mediastinal mass revealed a moderately differentiated adenocarcinoma similar in morphology to that found in the breast biopsy. Interestingly, the immunohistochemical study showed a strong positivity for CK8/18 and CK7, a focal positivity for CEA and a mitotic index of 60%. All other immunostains including CK20, CDX2 and breast tissue markers were negative. Based on these findings, a left anterior thoracotomy was performed to remove the mediastinal lesion.
On gross examination, the resected tumor measured 12 x 10 x 7 cm and weighed 99 g. It was well demarcated with no obvious signs of rupture. No definite capsule or lung parenchyma were identified. The external surface had a glistened variegated appearance with alternating yellowish and congested areas. On sectioning, the mass was unilocular with a predominantly smooth wall and contained grumous material with hair.
Multiple thickened bourgeon areas measuring up to 1.5 cm associated with small yellowish colored granules were discovered inside the wall and on its interior surface. No papillary excrescences were found.
Microscopically, the cystic wall consisted of fibrocollagenous tissue lined by cuboidal and/or tall columnar mucin secreting epithelium with areas of minimal chronic inflammation and vascular congestion (Figure 5). On sectioning of the thickened areas, mature elements of all three germ layers were found:
- mesodermal derivatives such as adipose tissue, cartilage, and muscle bundles,
- endodermal derivatives such as gastrointestinal tract tissue and ciliated bronchial tissue
- and ectodermal derivatives such as stratified squamous epithelium and sebaceous glands.
There were no immature teratomatous elements or other germ cell components associated. Furthermore, we noted multiple foci of atypical cells, arranged in groups or glands and surrounded by a reactive fibrous stroma. These cells contained abundant eosinophilic cytoplasm, sometimes with intracytoplasmic vacuoles and displayed a moderate degree of pleomorphism and atypia (Figure 5). The immunohistochemical profile was similar to that found in the breast biopsy and showed a positivity for cytokeratines, BerEP4 and CDX2, suggesting a digestive origin (Table 1).
A final diagnosis of a mature teratoma with somatic-type malignant transformation, most likely an adenocarcinoma, with secondary breast metastasis was concluded.
The patient’s postoperative course was uneventful and she was subsequently discharged. Unfortunately, the patient died a few months later.