The Histopathology of Breast Cancer- Part B

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

Medullary carcinoma

Definition

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.

Epidemiology

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.

Imaging

These tumors are well circumscribed and may represent a benign lesion.






Medullary carcinoma appears well circumscribed on mammogram.

Pathology

Gross

Medullary carcinomas are well circumscribed, soft, fleshy, with necrosis and haemorrhage.

Microscopy

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.

Invasive carcinoma with medullary features.
Medullary carcinoma with lymphoplasmacytic infiltrate and tumour cells with atypical nuclei.

Prognosis

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.

Treatment

Complete excision with adjuvant chemotherapy and radiation. 

Carcinoma with apocrine differentiation

Definition

Tumour which have >90 % cells with cytological or immunohistochemical features of apocrine cells. 

Epidemiology

It accounts for 1-4 % of all breast carcinomas.

Imaging

Imaging findings do not differ much from that of invasive ductal carcinoma.

Pathology

Gross

Cannot be distinguished from ductal carcinoma. Often multicentric.

Microscopic

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.

Image result for apocrine carcinoma breast type A

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.

Image result for GCDFP-15 apocrine carcinoma breast

Immunohistochemistry

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

Definition

Ductal carcinoma or lobular carcinoma that resembles gastric carcinoma with due to acidic mucin that fills the cytoplasm and displaces the nucleus.

Pathology

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.

Clinical features

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.

Image result for signet ring breast carcinoma
Signet ring lobular carcinoma

Metaplastic carcinoma

Definition

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

Epidemiology

These account for less than 5 % of invasive breast carcinomas.

Imaging features

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.

Pathologic features

Gross

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.

Microscopy

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.

Image result for metaplastic breast carcinoma
Low grade adenosquamous
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.

Image result for metaplastic fibromatosis breast carcinoma
Fibromatosis like metaplastic carcinoma
Squamous cell carcinoma

Consists of variable extent of squamous differentiation featuring pavemented tumor cells, with squamous whorls, keratinisation and intercellular bridges.

Image result for metaplastic breast carcinoma
Squamous component

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.

Image result for spindle cell breast carcinoma
Metastatic carcinoma with mesenchymal differentiation

The mesenchymal component of these tumours may include osteoid, chondroid, rhabdomyoid and neuroglial elements. 

Prognosis

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

Definition

Invasive carcinoma with papillary architecture greater than 90%.

Epidemiology

Extremely rare tumour in its pure form.

Image result for papillary breast carcinoma

Imaging

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.

Pathology

Image result for papillary breast carcinoma gross

Gross

Solid fleshy and friable appearance due to papillary formation.

C:\Users\sujoy\AppData\Local\Packages\Microsoft.Office.Desktop_8wekyb3d8bbwe\AC\INetCache\Content.MSO\806E1F86.tmp

Microscopy

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.

Prognosis

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

Definition

It accounts for less than 0.1% of all breast malignancies. It is similar histologically to salivary gland adenoid cystic carcinoma.

Imaging

Margins may be well defined or ill defined on mammogram. 

Epidemiology

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.

Pathology

Gross

They may appear greyish white, circumscribed, circular and nodular with cystic areas or maybe ill defined.

Microscopic

Prognosis

Excellent prognosis,  can be managed by wide excision alone.

Micropapillary carcinoma

Definition

Tumour is composed of small clusters of cells within clear stromal spaces and is seen at a mean age of around 59 years.

Clinical features

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.

Epidemiology

Less than 2% of invasive breast cancers

Pathology

Gross

Tumour has lobulated appearance

Microscopy

Avascular clusters of epithelial cells seen floating in mucinous material. These cells have abundant eosinophilic cytoplasm, round vesicular nuclei and prominent nucleoli.

Image result for micropapillary carcinoma breast
Clusters of tumour cells floating in mucinous material

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.

Prognosis

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.

Leave a Reply