The document discusses the histopathology of breast cancer, detailing the structure of the female breast, types of benign and malignant lesions, and classifications of breast carcinoma. It covers the progression from non-proliferative breast changes to various forms of carcinoma, emphasizing the importance of molecular classification for prognosis and treatment. Additionally, it reviews diagnostic approaches and the 'triple test' method for accurately classifying breast masses.

1. Histopathological
Interpretation of Breast
Cancer
Dr. Umme Kulsum Munmun
MD (Pathology)
Assistant Professor
Department of Pathology
Cumilla Medical College

2. • Female breast is composed of 15-
20 modified apocrine sweat
glands
• In resting adult breast, the
glandular portion is composed of
clusters of small secretory lobules
or acini ( lobular units)
• The lobules are connected by
small terminal ducts to the main
excretory or lactiferous ducts
opening into the nipple
• The surrounding stroma is of two
types : intralobular and
interlobular
• Each elements are the source of
both benign and malignant
lesions

3. Histology
• Two types of cells line the ducts and
lobules
 Luminal cuboidal cells-
produce milk
 Contractile
myoepithelial cells  lie on
the basement membrane 
assist in milk ejection
during lactation and
provide structural
support to the lobules
• The stroma is composed of loose
connective tissue and fat
• After menopause, the lactiferous
apparatus undergoes atrophy and
the stroma becomes more fibrous

5. Benign Epithelial Proliferations
 Classified into three groups
- non-proliferative breast changes
- proliferative breast diseases without atypia
- proliferative breast diseases with atypia

6.  Recent immunophenotypic and molecular studies indicated a
linear progression from normal epithelium through usual
hyperplasia, atypical hyperplasia and carcinoma in situ to invasive
cancer

7. Non- proliferative breast changes
 Non-proliferative breast changes (fibrocystic changes) include: cyst, fibrosis
and adenosis
 May present with irregular lumpy area
 Not associated with an increased risk for breast cancer

8.  Adenosis is defined as an increased number
of acini per lobule
 Preserved 2 cell layer (inner epithelial and
outer myoepithelial cells)

9.  Prominent sclerosing adenosis, one of the features of fibrocystic changes, is
demonstrated here by the appearance of a proliferation of small ducts in a fibrous
stroma. Although it is benign, the gross and mammographic appearance may
mimic carcinoma.

10. Sclerosing Adenosis

11. Proliferative breast disease
without atypia
 Lesions characterized by proliferation of epithelial cells without
atypia
 Associated with a small increase (1.5 to 2 times) in the risk of
subsequent carcinoma
 Commonly detected as mammographic densities, calcifications or
as incidental findings in biopsies performed for other reasons
 Also called ‘usual ductal hyperplasia’, ‘epithelial hyperplasia’,
‘epitheliosis’ etc

12. Usual Ductal Hyperplasia
The lumens are filled with
heterogenous , mixed population of
luminal and myoepithelial cell types
Nuclei are oval, normochromatic
Presence of peripheral elongated
clefts

13. Usual Ductal Hyperplasia:
Streaming effect, induced
by the oval cells arranged in
parallel bundles
Irregularly shaped bridges
connecting opposite
portions of the wall. Cells in
this bridges have oval
nuclei arranged parallel to
the long axis of the bridge

14. Proliferative breast disease with
atypia
 Associated (4 to 5 times) with moderately increased risk of
carcinoma
 Includes two forms: atypical ductal hyperplasia and atypical lobular
hyperplasia

15.  ADH can have all of the cytologic features seen in low-grade DCIS.
Architecturally, too, the lesions are similar, The differentiating
feature, however, is the extent of the process.
 Differentiation from low grade DCIS : size ≤ 2 mm, involvement:
less than 2 separate ducts or only a portion of involved duct

16. Atypical Ductal Hyperplasia

17. In ALH, the lobules are normal sized and still contain
identifiable lumina. This image shows the spectrum of
findings from ALH to LCIS.
• ALH is found in fewer than 5% of biopsies
• Incidental finding , no radiologic correlates
• ALH consists of cells identical to those of LCIS but the cells do not fill or
distend more than 50% of the acini within a lobule

18. Stromal tumor
Fibroadenoma

19. Phyllodes Tumour

20. Classification of Breast
Carcinoma
 In situ carcinoma:
- Ductal Carcinoma in situ (DCIS)
- Lobular Carcinoma in situ (LCIS)
 Invasive carcinoma:
- Invasive ductal carcinoma, not otherwise specified
- Invasive lobular carcinoma
- Tubular carcinoma
- Cribriform carcinoma
- Mucinous (Colloid) Carcinoma

21. - Medullary carcinoma
- Microinvasive carcinoma
- Papillary carcinoma
- Micropapillary carcinoma
- Apocrine carcinoma
- Metaplastic carcinoma
- Neuroendocrine carcinoma
- Inflammatory carcinoma
 Rare salivary gland type tumour:
- Acinic cell carcinoma
- Adenoid cystic carcinoma

22. Ductal Carcinoma In Situ
 Confined to the ductal-lobular system
 No evidence of invasion through the basement membrane into the
surrounding stroma Majority are non-palpable and detected
mammographically as microcalcifications (70 - 80%)
 Less frequently presents as palpable mass, nipple discharge, Paget
disease of the nipple
 8-10 times higher risk for subsequent development of invasive breast
carcinoma compared to general population

23.  Many morphologic variants exist:
- comedocarcinoma (High grade) and
- solid, cribriform, micropapillary, clinging etc
 Papillary carcinoma is a very distinct type, arise from large ducts
 Others originate in terminal duct lobular unit

24. Usual Ductal Hyperplasia DCIS with Cribriform Pattern:

25.  DCIS with Micropapillary Pattern:
 Papillary fronds and tufts lacking fibrovascular cores
projecting into duct lumen
 Tips of fronds may fuse, forming bridges and arcades

26.  Papillary DCIS:
 Papillary fronds containing prominent fibrovascular septa projecting into
duct lumen, papillary cores generally lack myoepithelial cell layer

27. DCIS with solid pattern:
Lumen of ducts or lobules filled with sheets of cohesive cells
Cells are evenly spaced especially in low or intermediate grade DCIS

28.  Flat or Clinging Pattern:
 1 - 2 layers of generally high grade malignant cells lining a gland with a large
empty lumen

29.  Comedo DCIS:
 Central expansile necrosis containing cellular debris, generally associated with
high grade DCIS, frequently associated with coarse microcalcifications

30. Lobular Carcinoma in Situ (LCIS)
 No specific clinical features
 Most times incidental finding in biopsy for some other mass
producing lesion such as a fibroadonoma
 No specific clinical features

31.  Classify as LCIS if lobular proliferation involves, expands or
distorts at least 50%+ acini in lobule; otherwise call atypical
lobular hyperplasia

32. LCIS

33.  E-cadherin immunohistochemistry is used commonly in surgical pathology
practice to help distinguish lobular carcinoma in situ from ductal
carcinoma in situ and
 invasive lobular carcinoma from invasive ductal carcinoma in histologically
problematic or indeterminate cases.

34. Loss of E- Cadherin in LCIS

35. Collision of DCIS and LCIS

36. Invasive ductal carcinoma (NOS)
 Most common type of invasive breast carcinoma (75 - 80%)
 Lacks features of any other subtypes (i.e. is a diagnosis of exclusion)

37. Microscopic (histologic) description
 Sheets, nests, cords or individual cells
 Tubule formations are prominent in well differentiated tumors
but absent in poorly differentiated tumors
 Tumor cells are more pleomorphic than lobular carcinoma
 Calcification in 60% of cases, variable necrosis
 Often DCIS (up to 80%), perineural invasion (28%)
 Mitotic figures are often prominent
 No myoepithelial cell lining (as seen in DCIS or benign lesions)
 Angiolymphatic invasion: In 35%

38. Invasive Ductal Carcinoma (NOS)

39. Angiolymphatic Invasion

40. Invasive Lobular Carcinoma
 Special subtype of invasive breast carcinoma characterized by
discohesive tumor cells arranged in single files or as individual
single cells

41. Invasive Lobular Carcinoma

42. Medullary Carcinoma
 Younger age
 less than 5% of all invasive breast cancers
 Well circumscribed, 2 - 3 cm in size, soft and fleshy (may
resemble fibroadenoma

43. Medullary Carcinoma

44. Tubular Carcinoma

45. Tubular Carcinoma
A well differentiated variant with very favorable prognosis
2 - 6% of all malignant breast tumors

46. Mucinous Carcinoma
 Rare tumor occurring in older women
 Also called-
Colloid carcinoma
Mucinoid carcinoma
Gelatinous carcinoma
Mucoid carcinoma
Mucinous adenocarcinoma
 Gross description
Well circumscribed mass of variable size (from < 1 cm to > 20 cm) with
gelatinous cut surface

48. Microscopic (histologic) description
 Clusters / nests of tumor cells with low or intermediate nuclear
grade floating in pools of extracellular mucin

49. Metaplastic Carcinoma
 Heterogeneous group of invasive breast carcinomas characterized
by differentiation of the neoplastic epithelium towards squamous
cells or mesenchymal looking elements, including spindle,
chondroid and osseous cells

50. Metaplastic carcinoma

51. Molecular Classification
 The diverse histologic appearances of breast carcinomas and
putative precursor lesions are the outward manifestations of the
complex genetic and epigenetic changes that drive
carcinogenesis.
 For prognostic and therapeutic purposes, the molecular
classification of breast cancer is more pronounced now-a-days
 There appear to be three major genetic pathways of
carcinogenesis

52.  ER-positive, HER2-negative cancers arise via the dominant
pathway of breast cancer development, constituting 50% to 65%
of cases.
 HER2-positive cancers arise through a pathway that is strongly
associated with amplifications of the HER2 gene on
chromosome 17q
 They constitute approximately 20% of all breast cancers and may
be either ER-positive or ER-negative

53. ER-negative, HER2-negative cancers comprise about 15% of breast cancers
overall, but are the most common tumor type observed in patients with
germline BRCA1 mutations

54. Diagnostic Approaches of CA Breast
 There are several competing approaches to breast biopsy:
• Biopsy by aspiration or fine-needle aspiration (FNA)
• Core needle biopsy
• Surgical excision biopsy or lumpectomy

55.  Excisional biopsy is the most traumatic and expensive, but offers the best
diagnostic material
 Some studies show that Core Needle Biopsy to be more accurate than
FNA in the diagnosis of non-palpable breast lesions and in the diagnosis
of LCIS and infiltrating lobular carcinoma
 Core biopsy is also favored in lesions that appear fibrotic or collagenous
 ER, PR , Her2 immunohistochemistry can be performed on CNB sample if
representative tissue is provided

56.  FNA is the least expensive, most rapid and the most versatile of the three
approaches
 FNAC usually distinguishes accurately non-neoplastic and benign breast
diseases from malignant diseases
 Approximately 98% of palpable masses with unequivocally malignant
cytology yield invasive carcinoma at excision, the remaining few are high
grade DCIS

57.  High grade DCIS is easily recognized as malignant in smears
 Smears from low-grade DCIS are usually reported as ‘atypical’ or ‘suspicious’
with a recommendation for Core Needle Biopsy or Open Biopsy
 Moreover, cytological examination on its own cannot definitely diagnose
invasion
 It must also be recognized that a CNB diagnosis of DCIS will be upgraded to a
diagnosis of invasive carcinoma at surgical excision in approximately 20% of
cases

58.  However, focal invasion in predominantly in situ carcinoma can only be
assessed by histological examination of the excised lesions
 If present, a second stage extended surgery usually follows
 Intraoperative frozen section may also be helpful to decide definitive surgical
management

59. The Triple Test
 In case of classification of breast masses as benign or malignant, physical
examination is about 70% to 90% accurate
 Mammography alone is 85% to 90% accurate
 FNA biopsy alone is 90% to 99% accurate
 No single test allows detection of all breast cancers
 Consequently, an important clinical approach to the diagnosis and
management of patients with breast abnormalities is the combination of all
three tests
 This diagnostic triad is known as the triple test

60.  All three parameters of the triad (clinical evaluation, mammography, FNAC)
are definitively malignant (MMM)  1% chance of error  Definitive therapy
including mastectomy can be considered
 All three are unequivocally benign (BBB)  98% chance is that the lesion is
indeed benign  patient can be safely followed up
 Any other, lesser combination must be carefully evaluated in clinical context
and histologically examined

61.  Some benign breast lesions mimic malignancy clinically or radiologically
which can be diagnosed easily on FNAC
 These include traumatic fat necrosis, granulomatous mastitis, duct ectasia,
subareolar abscess, intraductal papilloma etc
 FNAC save anxiety, trauma, time and money at a time