33 Special Types of Invasive Breast Carcinoma: Diagnostic Criteria ...

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of the breast. Lancet 1928;1:801-804. 11. Scarff TW, Handley RS. Prognosis in carcinoma of the breast. Lancet 1938;1:582-583. 12. Bloom HJG. Prognosis in carcinoma of the breast. Br J Cancer 1950;4:259-288. 13. Bloom HJG. Further studies on prognosis of breast carcinoma. Br J Cancer 1950;4:347-367. 14. Bloom HJG, Richardson WW. Histological grading and prognosis in breast cancer. Br J Cancer 1957;11:359-377. 15. Fisher EF, Sass R, Fisher B. Histological grading of breast cancer. Path Annu 1980; 15(1):239-251. 16. Doussal LE, Tubiana-Hulin M, Friedman S, Hacene K, Spyratos F, Brunet M. Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR). An improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 1989;64:1914-1921. 17. Simpson JF, Page DL. Status of breast cancer prognostication based on histopathologic data. Am J Clin Pathol 1994;102(Suppl 1):S3-S8. Basal-like and triple-negative breast cancers Breast cancer encompasses multiple entities with distinct morphological features and clinical behaviors – that is, diversity resulting from distinct genetic, epigenetic, and transcriptomic alterations. This is true for invasive ductal carcinomas of no special type (IDC-NST), wherein tumors of the similar histological appearance and grade may have different outcomes and responses to systemic therapy. This results from not only individual tumor characteristics, but also from patient-specific characteristics (such as immune and angiogenic response). These patient or tumor characteristics interact in poorly understood ways and determine the eventual natural history of the disease. Using gene expression microarrays, some have proposed a new taxonomy for breast cancer based on their molecular features. This microarray approach has identified at least five molecular breast cancer subtypes: 1) luminal A, 2) luminal B, 3) normal breast-like, 4) HER2 over-expressing, and 5) basal-like. Although incompletely -9-
studied, this taxonomy identifies subgroups of breast cancer that were to some extent already known and the stability or utility of the assigned subtypes has been questioned. Indeed, this taxonomy is not be used by UCSD oncologists. Nonetheless, the most robust distinction observed by microarray is between estrogen receptorpositive and ER-negative breast cancers, and none has generated as much interest as the basal-like group. Although there is no clear-cut histologically defined basal cell in breast epithelium, the myoepithelial cell is well defined. So-called basal-like breast cancer has been extensively reviewed, and there remains no internationally accepted definition for basal-like breast cancer. Some use microarraybased expression profiling to define basal-like breast cancers, whereas others use immunohistochemical markers. Unfortunately, direct comparisons between the proposed immunohistochemical markers and microarray-defined molecular subtypes are scarce. Immunohistochemical marker panels that have been proposed to define basal-like breast cancers include: (1) lack of ER, PR, and HER2 expression (“triplenegative” immunophenotype); (2) expression of one or more high-molecular-weight/ basal cytokeratins (CK5/6, CK14, and CK17); (3) lack of expression of ER and HER2 in conjunction with expression of CK5/6 and/or epidermal growth factor receptor (EGFR); and (4) lack of expression of ER, PR, and HER2 in conjunction with expression of CK5/6 and/or EGFR. These high-molecular-weight keratins also highlight myoepithelial cells. Despite the different definitions for basal-like breast cancers, these tumors may have somewhat distinctive clinical presentations, histological features, response to therapy, sites of distant relapse, and outcome. Basal-like tumors are heterogeneous, account for up to 15% of all breast cancers, affect younger patients, are more prevalent in African- American women, and often present as interval cancers. The majority classify as IDC- NST type, are high histological grade, have high mitotic indices, show central necrotic or fibrotic zones, have pushing borders, have conspicuous lymphocytic infiltrate, and often display medullary-like features. However, not all basal-like cancers are of the IDC-NST type. Indeed, the majority of medullary and atypical medullary, metaplastic, secretory, myoepithelial, and adenoid cystic carcinomas also have a basal-like phenotype. A subgroup of lobular carcinomas express high-molecular-weight cytokeratins, but may not show a basal- -10-
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33 Special Types of Invasive Breast
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Special Types of Invasive Breast Ca
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INVASIVE BREAST CARCINOMAS CONSIDER
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ER Neg. PR Neg. HER2 Neg. CK 5/6 Po
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Triple-negative Breast Carcinomas
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E-cadherin E-cadherin EGFR ++ ER ne
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ER/PR Positive HER2 Negative INVASI
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Tubulolobular Signet-ring Histiocyt
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Illustrative Example: 61 y/o female
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E-Cadherin ER PR 10/8/2011 17
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LCIS vs DCIS • Patients with lobu
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Examples of E-cadherin staining in
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Classic Low-grade DCIS - E-cadherin
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E-cadherin IHC CASE D 10/8/2011 25
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E-cadherin IHC CASE E 10/8/2011 27
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Literature Summary: Correlation of
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10/8/2011 31
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CD10 SMA MIB-1 10/8/2011 33
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Carter et al. Cancer 1977 & 1983
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Differential Diagnosis: 1. Invasive
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10/8/2011 39
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SYNAPTOPHYSIN SMA 10/8/2011 41
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Nassar et al. (AJSP 2006;30:501-7.)
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Special Types of Invasive Breast Ca
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Tubular carcinoma • It has been d
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Tubular carcinoma Histopathology
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Flat Epithelial Atypia When should
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Microglandular adenosis + reticulin
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mitosis ductal ductal, NST tubular
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Treatment • Breast conservation t
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Cribriform carcinoma Histopathology
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Cribriform carcinoma Prognosis •
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Cribriform Carcinoma Pearls of Path
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Clinicopathological features Mucino
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Case 4 Mucinous carcinoma Mixed muc
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Treatment • Breast conservation a
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Incipient mucocele-like lesion Cyst
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10/8/2011 73
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10/8/2011 75
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SMA Dx: Spindle-cell Breast Carcino
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Dx: Pure Squamous Carcinoma 10/8/20
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Osseous Differentiation (Osteosarco
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Spindle-cell Carcinoma of the Breas
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Phyllodes y Tumors Phyllodes Tumor
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Diagnosis: Benign g (Low-grade) Phy
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Diagnosis: Malignant (High-grade) P
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10/8/2011 91
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Page 97 and 98: Illustrative Case 10/8/2011 95
Page 99 and 100: SMA Calponin 10/8/2011 97
Page 101 and 102: Dx: Mixed Spindle-cell & Cl Classic
Page 103 and 104: Dx: Adenomyoepithelioma, Epithelioi
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Page 109 and 110: Case 1 • 40 year old female • B
Page 111 and 112: What is your diagnosis? 1. Invasive
Page 113 and 114: Case 4 • Irregular large breast m
Page 115 and 116: Case 6 • Needle core biopsy of a
Page 117 and 118: 343 What is your best diagnosis? 1.
Page 119 and 120: 349 Case 9 What is your diagnosis?
Page 121 and 122: Case 11 Case 11 Case 12 • A 68 ye
Page 123 and 124: Case 13 • Needle core biopsy of a
Page 125 and 126: What is your diagnosis? 1. Intracys
Page 127 and 128: What is your best interpretation? 1
Page 129 and 130: Case 18 What is your best interpret
Page 131 and 132: Case 20 • 35 year old female with
Page 133 and 134: Negative ER stain NEG ER Case 22
Page 135 and 136: What is your best interpretation? 1
Page 137 and 138: What is your diagnosis? 1. Secretor
Page 139 and 140: American Soiety of Clinical Patholo
Page 141 and 142: SPECIAL TYPES OF INVASIVE BREAST CA
Page 143 and 144: INVASIVE BREAST CARCINOMAS THAT ARE
Page 145: of lymphoid cells between sheets of
Page 149 and 150: molecular subtypes. Indeed, the pea
Page 151 and 152: In summary, basal-like breast cance
Page 153 and 154: Page et al. (15) described a pleomo
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Page 163 and 164: References (lobular carcinoma): 1.
Page 165 and 166: 25. Richter GO, Dockerty MB, Claget
Page 167 and 168: Breast Cancer Cooperative Group). L
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Page 171 and 172: whether these lesions are in situ o
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Page 179 and 180: outcome of patients with intracysti
Page 181 and 182: Case 3: History: A 73 year old fema
Page 183 and 184: cases. In this small tubular carcin
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Page 187 and 188: Sclerosing papillary proliferations
Page 189 and 190: 9. Bondeson L, Lindholm K. Aspirati
Page 191 and 192: 43. Green I, McCormick B, Cranor M,
Page 193 and 194: mucinous carcinoma (7,11,12,14). In
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with long-term follow-up [Abstract]
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cystic hypersecretory duct carcinom
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considerable secretion and/or morph
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4. Tavassoli FA, Norris HJ. Secreto
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Case 6: History: 66 year old female
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Adenoid cystic carcinoma (AdCC) is
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Because more than half of adenoid c
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Another family of salivary gland-ty
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Collagenous spherulosis is a recent
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cases: review of the literature and
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Case 7 the breast associated with l
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size (14). Metaplastic breast carci
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adenoma by others who prefer to avo
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survival rate than is usually repor
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it arises in other soft tissue site
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implies a relative risk for develop
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sclerosing adenosis wherein the str
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overgrowth (136). While acknowledgi
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As noted above, any soft-tissue sar
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J Med 73:1078-1082, 1973. 11. Barne
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40. Thorner PS, Kahn HJ, Baumal R,
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75. Fekete P, Petrek J, Majmudar B,
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microscopic, ultrastructural, and i
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2006 Apr;30(4):450-6 143. Liberman
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Case 8 Case history: A 50 year old
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secondary peripheral tumor nodules
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Definitive diagnosis of medullary c
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Pathol 1988;19:1340-6. 12. Rosen PP
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40. Di Bonito; Royen PM, Ziter FMH.
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Am J Clin Pathol 1979;72:383-389. 1
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