Sclerosing lesions and breast lesions with sclerosis (SL/BLWS), characterised by adenosquamous proliferation or equivalent
| Details | Radial scar/complex sclerosing lesion (RS/CSL) | Infiltrating epitheliosis (IE) | Sclerosing papilloma (SP) | Ductal adenoma—with sclerosis (DA) | Nipple adenoma—sclerosing papillomatosis pattern (NA) | Subareolar sclerosing duct hyperplasia (SSDH) | Syringomatous tumour (ST) | Low-grade adenosquamous carcinoma (LGASC) |
| Nature | Benign | Benign—variant of RS/CSL | Benign | Benign | Benign | Benign | Generally indolent, locally infiltrative | Generally indolent, locally infiltrative, rarely metastasizing |
| Localisation | Breast parenchyma (central or peripheral) | Breast parenchyma (central or peripheral) | Breast parenchyma (central or peripheral) | Breast parenchyma, (central or peripheral) | Nipple | Beneath nipple or areola | Nipple, may invade breast parenchyma if large | Breast parenchyma, rarely involves nipple |
| Size | Varies, RS <10 mm, CSL >10 mm | Varies | Varies | Varies | Varies | Varies | Varies | Varies |
| Age at presentation | Broad range | Broad range | Broad range | Broad range, but mainly sixth decade | Broad range | Broad range, but mainly sixth decade | Broad range | Broad range |
| Presentation | Radiological abnormality or mass if large | Radiological abnormality or mass if large | Typically a radiological abnormality | Palpable mass and/or a radiological abnormality | Ulceration, nipple discharge, visible lesion or palpable thickening of nipple | Palpable mass and/or a radiological abnormality | Often as a palpable mass | Radiological abnormality or palpable mass if large |
| Histological architecture | Stellate, floral architecture, particularly if smaller (RS), larger lesions (CSL), may be more complex and disorganised | Non-stellate, irregular outline, infiltrative | May be confined to a duct or duct system or extend beyond duct, rounded to variably distorted and sclerotic | Rounded and contained within a duct or appearing to infiltrate into sclerotic periductal stroma | Mass forming, rounded to irregular, infiltrative appearing periphery | Irregular outline, central scarring | Irregular outline, infiltrative, typically confined to dermis and nipple stroma | May appear stellate and RSL like, typically has an irregular outline with invasion of breast parenchyma (adipose tissue) |
| Basic histological features | Smaller lesions (RS) show central nidus surrounded by a rosette-like corona comprising proliferative or fibrocystic disease. CSL may show multiple niduses. Nidus in early lesions contains ASP in mucoid, inflammatory stroma; late lesions characterised by hypocellular, fibroelastic nidus/zones | Predominant features is UDH/UDH-like proliferation with jagged edges an often proliferative growth pattern, variably accompanied by ASP (miniature LGASC-like proliferation) | Intraduct papilloma is the base lesion, distorted by sclerosis associated with variable ASP | Solid intraduct papilloma-like lesion is the base lesion, with variable sclerosis and distortion. Can appear stellate in appearance (eg, if sclerosis occurs centrally) | Papillomatosis pattern / florid UDH within ducts is base lesion, with variable sclerosing distortion | Variable papillary, ductal and stromal proliferation, central sclerosing papillary proliferation, irregular extension into small ducts at the periphery, small cysts with hyperplasia seen at the periphery of some lesions | Infiltrating ducts with squamous and glandular differentiation within a desmoplastic background. Stroma may be less spindled and less cellular and lymphoid aggregates less common than in LGASC, but disputed | Infiltrating ducts with squamous and glandular differentiation within a desmoplastic background. May show more cellular, spindle cell rich stroma than ST and lymphoid aggregates, but disputed |
| Prominence of ASP or equivalent proliferation | Characteristic within nidus of early RSL, diminished or absent in end-stage/late RSL | Varies, may be inconspicuous | Varies, may be more visible in ‘early’ lesions | Varies, may be more visible in ‘early’ lesions | Varies | Varies, may be more visible in ‘early’ lesions | Predominant feature | Predominant feature |
| Pattern of ASP or equivalent proliferation | Confined to nidus in early RSL. Diminished or totally absent in late RSL | Not confined to a central nidus, may be multiple. With prominent sclerosis it may be inconspicuous (essentially CSL-like pattern with UDH /UDH-like process predominating) | Within centre or periphery of lesion, but with prominent sclerosis it may be inconspicuous | Within centre or periphery of lesion, but with prominent sclerosis it may be inconspicuous | May be focal or scattered throughout lesion, but with prominent sclerosis it may be inconspicuous | May be central within lesion, but with prominent sclerosis it may be inconspicuous | Infiltrative within dermis and nipple stroma | Infiltrative within breast parenchyma. Can show limited infiltration and mimic an early, proliferative phase RSL |
| Immunohistochemistry | ASP is triple negative for ER, PR and HER2, shows inconsistent presence of myoepithelial-like cells with myoid markers (eg, SMA, myosin, calponin), shows coexpression of high molecular weight cytokeratins (eg, CK5/6) and p63. Myofibroblastic stroma expresses myoid markers, typically cuffing epithelium. Corona shows intact myoepithelial layer and heterogeneous ER and PR expression | UDH and UDH-like proliferation expresses CK5/6. Myoepithelial cells generally absent from UDH-like proliferation, often lacking expression of p63 and myoid markers. ASP when present stains as described earlier | Bilayer of epithelium and myoepithelium demonstrable, heterogeneous ER and PR expression. UDH expresses CK5/6. ASP stains as described earlier. Sclerosing areas show inconsistent myoepithelial component | Essentially same as sclerosing papilloma | Essentially same as sclerosing papilloma | Essentially same as sclerosing papilloma. Myoepithelial cells less demonstrable at lesions periphery | Triple negative for ER, PR and HER2. Luminal glandular and squamous immunophenotype, and an outer myoepithelial-like layer expressing p63, CK5/6 and CK14, but generally not myoid markers. The latter are expressed by desmoplastic stroma | Triple negative for ER, PR and HER2. Luminal glandular and squamous immunophenotype, and an outer myoepithelial-like layer expressing p63, CK5/6 and CK14, but generally not myoid markers. The latter are expressed by desmoplastic stroma which may form a lamellar cuff around tumour, or form sheets. Some spindle cells may express cytokeratin and p63 |
| Molecular genetics | PIK3CA mutations | PIK3CA and PIK3R1 mutations | PIK3CA/AKT pathway mutations (IP—sclerosis unspecified) | AKT1, GNAS and PIK3CA mutations | PIK3CA, KRAS and BRAF mutations | Unknown | Unknown | PIK3CA mutations and EGFR amplification |
| Treatment | Excision if large, symptomatic or associated high-risk lesion present, otherwise radiological surveillance | Excision if large, symptomatic or associated high-risk lesion present, otherwise radiological surveillance | Excision if large, symptomatic or associated high-risk lesion present, otherwise radiological surveillance | Excision if large, symptomatic or associated high-risk lesion present, otherwise radiological surveillance | Excision | Excision if large, symptomatic or associated high-risk lesion present, otherwise radiological surveillance | Excision | Excision |
ASP, adenosquamous proliferation; CSL, complex sclerosing lesion; EGFR, epidermal growth factor receptor; ER, oestrogen receptor; PR, progesterone receptor; RS, radial scar; UDH, usual ductal hyperplasia.