MALIGNANT TUMORS

Carcinoma of the breast

• Incidence: rarely develops before the age of 25 years, age peak during perimenopausal years.
• Risk factors: positive family history, long reproductive life- means early menarché and late menopause, more frequent in nulliparous than in multiparous women, exogenous estrogens -still controversial, but some data show moderately increased risk with high-dose therapy of menopausal symptoms (HRT-hormone replacement therapy), oral contraceptive -no clear-cut increased risk, obesity- increased risk attributed to synthesis of estrogens in fat deposits, geographic influences- five times more common in the States than in Japan
• Genetics and family history: about 5-10% ca is believed to be related to inherited gene mutations
• BRCA-1-relatively recently discovered gene on chromosome 17q21
• BRCA-2-gene located on chromosome 13q12-13, both genes are suppressor, they are responsible of familial breast cancer- screening for mutation of these genes in women with positive history
• Classification- two major categories- invasive (infiltrating) and noninvasive

most tumors are invasive, careful examination and screening mammography- increases a number of in situ diagnosed tumours

Classification of breast cancer:

1. noninvasive carcinoma
• intraductal carcinoma- ductal ca in situ
• intraductal papillary carcinoma
• lobular carcinoma in situ
2. invasive carcinoma:

• invasive ductal carcinoma
• invasive lobular carcinoma
• medullary carcinoma
• colloid carcinoma (mucinous, gelatinous)
• Paget carcinoma of the nipple
• tubular carcinoma
• invasive papillary carcinoma
• adenoid cystic carcinoma
  

• Features common to invasive carcinomas

• local invasion into adjacent structures- tumor fixation, retraction of the nipple, dimpling of the skin
• lymphatic invasion-causes lymph node metastases- about two-thirds of breast carcinomas present with lymph node metastases- axillary, supraclavicular and mammary nodes often involved
• blood vessel invasion- metastases to the skin, lung, liver, bone marrow, etc.

Factors influencing the prognosis

• tumor size- minimal cancer is less than 1 cm -associated with favorable prognosis, most tumors are detected 4cm in diameter
• lymph node spread and number of positive nodes- two thirds of breast cancers are detected as lymph node positive- 5year survival for lymph node negative patients-80%, for positive patients only 50%
• histological grading- degree of differentiation, nuclear polymorphism, mitotic count
• estrogen/progesterone status-70% breast cancers contain ER/PR
• proliferative activity-
• presence of activated gene-c-erbB-2/HER-2/neu overexpression of transmembrane oncoprotein-in about 15% of breast cancers- more aggressive behavior
  

Grading and staging of breast cancer

Cancers may be first divided as follows:

• nonmetastasizing tumors- intraductal or comedocarcinoma without stroma invasion, in situ lobular carcinoma

• uncommonly metastasizing tumors-pure colloid, medullary cancer, tubular adenocarcinoma, adenoid cystic ca

• metastasizing- all other types

STAGING: TNM system- size of primary tumour- nodal involvement, distant metastases

Ductal carcinoma - the most common type of breast carcinoma-over 90% of breast ca arise within the ducts

• may exist as ductal carcinoma in situ or invasive

• noninvasive type = carcinoma in situ -tumor restricted to intraductal proliferation without penetrating the basement membranes of ducts- ducts may be dilated and filled with carcinoma cells-

• sometimes central necroses with comedo-like appearance -called comedocarcinoma

• Invasive ductal carcinoma

• Grossly- the tumor is poorly defined, firm, palpable mass -hard consistency
• some tumors exhibit marked fibroplasia- increased production of dense fibrous tumor stroma- desmoplastic carcinoma-skirrhus
• attachment to adjacent structures, fixation to the pectoral fascia, dimpling of the skin, retraction of the nipple
• on section-the tumor is retracted below the cut surface
• histologically: tumor consists of anaplastic duct epithelial cells disposed in cords, solid foci, tubules, glandular and cribriform anastomosing structures
• frequent finding- perineural and intravascular invasion - breast cancer has usually high propensity for dissemination

Lobular carcinoma

• may exist as lobular carcinoma in situ or invasive
• In situ -histologically distinctive proliferative lesion characterized by proliferation in one or more terminal duct-acinar units
• in most cases- asymptomatic, incidental finding, not palpable, no picture on mammo
• composed of the cells loosely cohesive, that are uniform in size, small, round to oval in shape, with low mitotic rate
• it is not a precancerous lesion, it is associated with slightly increased risk of ductal or lobular invasive ca
• Invasive- these tumors are of particular interest because they may be bilateral and/or multicentric within the same breast
• grossly: poorly circumscribed, rubbery
• histologically: consists of single layered cords of cancer cells infiltrating the breast- often with skirrhous pattern indian file pattern
• the cells are small, uniform with little cytologic polymorphism

Medullary carcinoma

• this variant is rare, accounts for about 1% of all breast carcinomas
• tends to produce larger masses-of soft consistency
• on section-soft, fleshy appearance, with foci of necroses and hemorrhages
• histologically: carcinoma is characterized by solid syncytium-like sheets of large cell with vesicular nuclei, frequent mitoses, and by abundant lymphocytic infiltration in the stroma, these tumors do not have desmoplasia
• prognosis is better than that of ductal cancer- 10-year survival is 70 to 90%

Colloid (mucinous) carcinoma

• this variant tends to occur in older women, the tumour grows slowly
• grossly-large gelatinous mass, the tumor is extremely soft
• histologically: composed of large lakes of mucinous extracellular matrix- floating within the mucin there are small islands of cancer cells
• better prognosis

Paget disease of the nipple

• is a special form of ductal breast cancer that arises in major ducts and extends to the skin of the nipple
• grossly: erosions and exematoid changes of the nipple-with discharge
• histologically: the squamous epithelium of the skin is infiltrated by carcinoma cells- Paget cells
• these cells are large, with pale cytoplasm and many mitoses
• careful studies often reveal the presence of ductal invasive or noninvasive breast cancer.
  

Category: Pathology Notes