Lobular carcinoma in situ

— uniform cells populating the lobule.

— >50% of the acini in the lobule expanded and filled.

— potentially multifocal (70%) and bilateral (30-40%).

— epithelial proliferation of lesser extent (e.g. with preservation of lumina) is designated atypical lobular hyperplasia.

Luminal Polarization Dcis

Figure 22.2. Ductal carcinoma in-situ (DCIS) versus atypical ductal hyperplasia (ADH) versus florid hyperplasia without atypia (FHWA): cytology and histology. DCIS features smooth, punched-out luminal borders within involved basement-membrane-bound space. The cytological features are regular and present throughout the entire population of at least two basement-membrane-bound spaces. FHWA is the most densely cellular and extensive of the proliferative disease without atypia lesions, also called "papillomatosis". There are ragged, often slit-like luminal borders. The nuclei throughout the involved area show variablity and tendency to a swirling pattern, as illustrated. ADH has features predominantly of non-comedo, cribriform DCIS, but also some features of proliferative disease without atypia or normally polarized cells within the same basement-membrane-bound space. (Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia. Hum Pathol 1992;23:1095-1097, copyright © 1992, with permission from Elsevier)

Figure 22.2. Ductal carcinoma in-situ (DCIS) versus atypical ductal hyperplasia (ADH) versus florid hyperplasia without atypia (FHWA): cytology and histology. DCIS features smooth, punched-out luminal borders within involved basement-membrane-bound space. The cytological features are regular and present throughout the entire population of at least two basement-membrane-bound spaces. FHWA is the most densely cellular and extensive of the proliferative disease without atypia lesions, also called "papillomatosis". There are ragged, often slit-like luminal borders. The nuclei throughout the involved area show variablity and tendency to a swirling pattern, as illustrated. ADH has features predominantly of non-comedo, cribriform DCIS, but also some features of proliferative disease without atypia or normally polarized cells within the same basement-membrane-bound space. (Page DL, Rogers LW. Combined histologic and cytologic criteria for the diagnosis of mammary atypical ductal hyperplasia. Hum Pathol 1992;23:1095-1097, copyright © 1992, with permission from Elsevier)

Distinction between DCIS and lobular carcinoma in situ (LCIS) is not always easy, e.g. lobular cancerization by low-grade DCIS and, rarely, mixed lesions occur. Loss of E-cadherin expression favours a lobular proliferation.

Microinvasion

— <1 mm from the adjacent basement membrane with infiltration of non-specialized interlobular/interductal stroma.

— the presence of multiple foci of microinvasion should be noted, but it is classified according to the largest focus and not the sum total of them.

Minimal invasive cancer

— variably defined as <0.5cm or <1cm maximum dimension. Invasive carcinoma

Ductal

— no specific type (NST): 70-75% of breast cancer. Lobular

— classical: 40%; single files of small cells/targetoid periductal pattern/AB-PAS positive intracytoplasmic lumina.

Figure 22.3. Schematic demonstration of diagnostic criteria for lobular carcinoma in-situ (LCIS). There is distention and distortion of more than half the acini, and an absence of central lumina. When these changes are less well developed (i.e. <50% of acini involved) atypical lobular hyperplasia (ALH) is diagnosed. Note that the pagetoid spread into adjacent ducts is more common in LCIS, but may be seen in ALH. (Page DL, Kidd TE, Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991;22:1232-1239, copyright © 1991, with permission from Elsevier)

Normal

LCIS ALH

Normal

LCIS ALH

Figure 22.3. Schematic demonstration of diagnostic criteria for lobular carcinoma in-situ (LCIS). There is distention and distortion of more than half the acini, and an absence of central lumina. When these changes are less well developed (i.e. <50% of acini involved) atypical lobular hyperplasia (ALH) is diagnosed. Note that the pagetoid spread into adjacent ducts is more common in LCIS, but may be seen in ALH. (Page DL, Kidd TE, Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991;22:1232-1239, copyright © 1991, with permission from Elsevier)

— alveolar: nested pattern of 20 or more cells.

— trabecular: bands of cells two to four across.

— pleomorphic: classical pattern but with cytological atypia.

— mixed: 40%; more than one component of these types but each is <80% of the tumour area.

— tubulolobular: classical pattern with focal microtubules which are less distinct than in tubular carcinoma.

Special types

— tubular: round, ovoid, angular tubules/single cell layer/cytoplasmic apical snouts/fibrous stroma.

— cribriform: invasive cords and islands with the morphology of cribriform DCIS comprising punched out lumina and cytoplasmic apical snouts.

— colloid (mucinous): pushing margins, extracellular mucin with small clusters (10-100 cells) of uniform epithelial cells.

— papillary: encysted (intracystic) in-situ or invasive. Invasion is either (a) a dominantly invasive carcinoma with a pushing margin and papillary pattern, or (b) an encysted papillary carcinoma with focal invasion and the invasive component can be papillary or ductal, NST. Note also invasive micropapillary carcinoma (micropapillae without cores set in clear spaces—the "inside-out" tumour with an external rim of apical cytoplasm), which correlates with lymphovascular and axillary node metastases. Also seen as a component of 5% of ductal, NST tumours.

— medullary, classical: sharply circumscribed margin, >75% is pattern-less tumour cell syncytium with grade 3 cytology, peri-/intratumoral stromal lymphoplasmacytic infiltrate with absence of glands and scant fibrous stroma.

— medullary, atypical: contains up to 25% ductal, NST, or an irregular margin with focal infiltration, or adjacent DCIS. Probably better regarded as invasive ductal, NST, with medullary features. The term medullary-like carcinoma has been suggested to encompass both classical and atypical medullary cancers, particularly as the observer reproducibility rates are so low.

Mixed types

— mixed differentiation ductal and lobular.

— tubular mixed—stellate mass, central tubules with peripheral less differentiated adenocarcinoma.

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