Although this article has been written with medical professionals in mind, we have left ample opportunity for the concerned patient/caregiver to know more about a specific histopathological diagnosis, especially by incorporating prognosis (the outcome) and clinical features to expect in a certain tumor.
Continuing from The Histopathology of Breast Cancer- Part A
Has an incidence of 1-10 % and there is considerable inter-observer variation in this type of tumour and diagnosis depends on the type of classification system employed. This tumour includes:
- classical medullary carcinoma
- atypical medullary carcinoma and
- invasive carcinoma of no special type.
Classical medullary carcinoma accounts for less than 1 % of all invasive breast cancers. The rest are invasive carcinomas and atypical forms with medullary features. Patients usually belong to younger age groups.
These tumors are well circumscribed and may represent a benign lesion.
Medullary carcinoma appears well circumscribed on mammogram.
Medullary carcinomas are well circumscribed, soft, fleshy, with necrosis and haemorrhage.
Microscopy shows the presence of lymphoplasmacytic infiltrate, intermingling with high grade tumour cells in a sheet like pattern with very little stroma. There maybe mitosis, necrosis and bizarre giant cells(Invasive cribriform pattern is most among invasive breast carcinomas for osteoclast like giant cells). These tumours are usually triple negative and show mutation for p53. The tumour cells are poorly differentiated and have a syncytial pattern, this tumour is quite rare when strict diagnostic criteria are followed. They are mostly seen in younger patients and those with BRCA1 mutations. Despite their aggressive histologic appearance they have a more favourable prognosis than infiltrating ductal carcinoma.
Tumours with dense lymphocytic infiltrates are more likely to respond to chemotherapy. Classical medullary features have better prognosis than stage matched triple negative carcinoma, with 10 year survival rates exceeding 80%. When lymph nodes are present(>= 4 nodes) or if the patient has BRCA1 mutations, the prognosis becomes unfavourable.
Complete excision with adjuvant chemotherapy and radiation.
Carcinoma with apocrine differentiation
Tumour which have >90 % cells with cytological or immunohistochemical features of apocrine cells.
It accounts for 1-4 % of all breast carcinomas.
Imaging findings do not differ much from that of invasive ductal carcinoma.
Cannot be distinguished from ductal carcinoma. Often multicentric.
Growth pattern is similar to ductal carcinoma. Only the cells appear different. The cells typically have apocrine morphology with granular cytoplasm and enlarged nucleus with multiple nuclei. Necrosis and abundant mitoses are present in high grade lesions.
The cells are classified into Type A and Type B:
Type A: Abundant granules, intensely eosinophilic and PAS positive with diastase resistance. Nuclei are globoid and hyperchromatic. They have abundant nucleoli.
Type B: Vacuoles present in the cytoplasm giving a foam like appearance, and resemble histiocytes. Nuclear features are similar to Type A.
A large number of these tumours are positive for GCDFP-15. These tumours show positivity for CEA, and have been reported to express CK7, 8 AND 18. 50% of these tumours express CK20. Majority are hormone ER/PR negative and are positive for androgen receptors, this feature has been recognised as the ‘typical’ apocrine phenotype.
GCDFP-15 staining 50% show HER2 overexpression.
Breast carcinoma with signet cell differentiation
Ductal carcinoma or lobular carcinoma that resembles gastric carcinoma with due to acidic mucin that fills the cytoplasm and displaces the nucleus.
Signet ring cells are present. Favour ductal carcinoma if hypercellular and high nuclear grade with tubule formation.
Favour lobular carcinoma if hypocellular, and mild to moderate nuclear grade. Mostly positive for mucin and ER/PR positive.
Rare tumour, associated with poor prognosis with metastasis to GI tract and female genital tract.
Maybe metastatic from GI- If metastatic then signet cells will be positive for CDX2, ER negative, no DCIS.
Signet ring cell variant of lobular carcinoma- no DCIS, ER+ve and E-cadherin negative.
These are a heterogenous group of neoplasms with components other than epithelial, glandular.
WHO has classified metaplastic carcinoma into the following:
- Low grade adenosquamous carcinoma
- Fibromatosis like metaplastic carcinoma
- Squamous cell carcinoma
- Spindle cell carcinoma
- Carcinomas with mesenchymal differentiation
- Myoepithelial carcinoma
These account for less than 5 % of invasive breast carcinomas.
Large, lobulated masses with partially well and ill-defined margins on imaging. Sonography may show cystic areas within the tumour due to necrosis or haemorrhage.
The tumour is well circumscribed, with a median size of 3-4 cm, usually firm, nodular. Squamous or chondroid areas are pearly white on cut surface.
Low grade adenosquamous cell carcinoma
Consists of nests and irregular, angulated epithelial tubules, with squamous differentiation and may form whorls or appear as islands with keratinisation. These islands invade the stroma and are surrounded by a lymphocytic infiltrate. Immunohistochemistry is positive for p63 and high molecular weight keratin. HER2 is usually negative.
Fibromatosis like metaplastic carcinoma
Low grade tumour, that closely resembles fibromatosis. It consists of long intersecting fascicles of spindle shaped cells with slender nuclei extending between breast lobules. IHC shows basal keratins and p63 positivity. These tumours are triple negative.
Squamous cell carcinoma
Consists of variable extent of squamous differentiation featuring pavemented tumor cells, with squamous whorls, keratinisation and intercellular bridges.
Cystic degeneration maybe seen. Giant cell reaction to keratin debris maybe seen. The acantholytic variant of squamous cell carcinoma can resemble angiosarcoma. The diagnosis of squamous cell carcinoma of the breast requires exclusion of skin primary or metastasis from elsewhere.
Spindle cell carcinoma
Spindle cells with moderate to marked nuclear pleomorphism and mitosis arranged in interlacing fascicles.An inflammatory infiltrate may accompany the malignant spindle cells. IHC shows p63 and high molecular weight keratin.
Metastatic carcinoma with mesenchymal differentiation
The mesenchymal component of these tumours may include osteoid, chondroid, rhabdomyoid and neuroglial elements.
Low grade adenosquamous and fibromatosis like metaplastic carcinomas behaving more indolently. May not respond to chemotherapy and have a worse prognosis than triple negative breast cancer. They may metastasize to the brain through hematogenous route.
Invasive papillary carcinoma
Invasive carcinoma with papillary architecture greater than 90%.
Extremely rare tumour in its pure form.
Radiological or palpable mass. Spiculations are rare, and abnormal microcalcifications may be seen. On ultrasound solid cystic mass may be seen, with papillary projections and internal echoes due to cellular debris and haemorrhage.
Solid fleshy and friable appearance due to papillary formation.
Papillary fronds are seen that invade into the surrounding stroma causing stromal dysplasia and inflammation at the advancing tumour front. Circumscribed, delicate and fibrovascular stroma. Cells have moderate to abundant cytoplasm, low/intermediate histological grade.
These cells stain positive for mucicarmine, alcian blue, and PAS.
IHC- ER, GCDFP-15, synaptophysin and neuron specific enolase.
Highly invasive form of breast cancer that has high chances of lymph node spread even when small in size. Prognosis is related to grade and stage.
Adenoid cystic carcinoma
It accounts for less than 0.1% of all breast malignancies. It is similar histologically to salivary gland adenoid cystic carcinoma.
Margins may be well defined or ill defined on mammogram.
It’s a rare tumour that is mostly seen in 25-80 years age group. Half these tumours are in nipple areola complex. This tumour tends to be associated with a favourable prognosis even when the tumour size is large.
They may appear greyish white, circumscribed, circular and nodular with cystic areas or maybe ill defined.
Excellent prognosis, can be managed by wide excision alone.
Tumour is composed of small clusters of cells within clear stromal spaces and is seen at a mean age of around 59 years.
Early nodal metastasis is seen due to reversal of cellular polarity and detachment of the cells from the stroma.
MUC1, Sialyl Lewis X and CD15 exhibits the reversed polarity. The lymphocytes that infiltrate the tumour lack cytotoxic phenotype.
Less than 2% of invasive breast cancers
Tumour has lobulated appearance
Avascular clusters of epithelial cells seen floating in mucinous material. These cells have abundant eosinophilic cytoplasm, round vesicular nuclei and prominent nucleoli.
Lymphovascular invasion seen. Psammoma bodies are often present. There are no mitoses, no necrosis and no lymphocyte invasion.
IHC- these tumours stain positively for MUC1,ER/PR/HER2, p53,bcl2, GCDFP-15.
Very poor prognosis, majority of patients have lymph node metastasis at the time of presentation, with a very high recurrence rate and mortality rate. Focal component of these tumours are found in 6 % of all breast carcinomas, and their presence indicates a poor prognosis irrespective of the amount of micropapillary component. Presence of micropapillary component mucinous tumours have no clinical significance.