Encyclopedia of Pathology

Living Edition
| Editors: J.H.J.M. van Krieken

Complex Sclerosing Lesion

  • Anna SapinoEmail author
  • Balmativola Davide
Living reference work entry

Latest version View entry history

DOI: https://doi.org/10.1007/978-3-319-28845-1_4701-2



Complex Sclerosing Lesion (CSL) is a benign proliferation of the breast. While the term “radial scar” (Radial Scar) is typically reserved for small lesions (<1 cm), the term “complex sclerosing lesion” refers to a larger scar lesion (≥1 cm) characterized by fibroelastosis, sclerosis, and sclero-hyalinosis with entrapped ducts and a variety of epithelial structures with a complex pattern of growth, which can include intraductal papillomas, sclerosing adenosis, and usual-type ductal hyperplasia (Racz et al. 2017; Ellis and Simpson 2012; Eusebi and Millis 2010; Kennedy et al. 2003).

Clinical Features

Occasionally, CSLs may be palpable firm irregular masses (Hicks and Lester 2017) or a radiological finding of a mass with spiculated margins, but more commonly CSLs cause architectural distortion on imaging, frequently containing microcalcifications. These radiological patterns may be indistinguishable from invasive carcinoma. On ultrasound, CSL is seen as hypoechoic area or mass and at Magnetic Resonance Imaging (MRI) as an irregular enhancing lesion, usually with lower enhancement than invasive carcinoma (Hicks and Lester 2017).
  • Incidence

    Some authors suggest CSLs are not uncommon, being present in 14–28% of autopsy studies. However, the literature reports that only 0.03–0.09% of all diagnosis performed on core needle biopsies are CSLs. The majority of patients have multiple lesions and almost 50% have bilateral CSLs (Hicks and Lester 2017).

  • Age

    In analogy to radial scar, CSLs are lesions mainly detected during screening (mean age 50 years).

  • Sex

    CSLs are found in female breasts, but very occasionally CSL occurs in male breasts.

  • Site

    No specific site had been described as concerns laterality or quadrant of the breast.

  • Treatment

    The management of radiologically detected CSL is still controversial because the reported incidence of malignancy on excisional specimens following a diagnosis of CSL/RSL on core needle biopsy (CNB) varies widely, between 0% and 23% (Nakhlis et al. 2018). However, the majority of cancers associated with CSL are small, well-differentiated invasive carcinoma and low grade DCIS. On the other hand, some authors suggest that CSLs are associated with considerable risk of finding breast carcinoma in adjacent tissue, prompting recommendation for excision (Kennedy et al. 2003). In conclusion, if epithelial atypia is present on CNB, excision is recommended due to the risk of having malignancy associated to the CSL. It is possible to proceed with observation when radiological and pathological features agree on CSL diagnosed on vacuum-assisted CNBs in the absence of other associated high risk lesions (Racz et al. 2017). CSLs diagnosed on excisional surgery specimens do not require additional treatment (Patterson et al. 2004).

  • Outcome

    As above reported CSL itself is considered a proliferative benign lesion which exhibits various secondary alterations in the epithelium and carries an approximately twofold increased risk of breast cancer (Racz et al. 2017). For this reason, CSLs are diagnosed as “lesion of undetermined risk” on core biopsies.


At difference with radial scar, CSLs are generally of sufficient size to produce an irregular firm mass, of yellow-white color, indurated, sometimes with central retraction. The central core is usually firmer than the area of radiating arms; most lesions are <2 cm. The gross appearance may be indistinguishable from that of an invasive carcinoma (Ellis and Simpson 2012); nevertheless, CSLs are usually firm but not as hard as invasive carcinomas.


CSLs are heterogeneous lesions, characterized by lobulocentric proliferations and varying degrees of proliferative epithelial changes: cysts, epitheliosis/usual type hyperplasia, apocrine metaplasia, and sclerosing adenosis (Racz et al. 2017; Ellis and Simpson 2012). All these lesions may be associated with cytological atypia.

At low magnification, two different regions can be identified, although not pathognomonic of CSL:
  • Central nidus: It is formed by hyalinized collagen stroma with elastosis entrapping and distorting tubules (two cell layers are retained) (Fig. 1, H&E).

  • Corona: Sclero-hyalinized bands of connective tissue radiating from central nidus and containing distorted tubular structures, frequently pointed and of different size. These bands dissect normal parenchyma and/or cystic lobules and/or lobular structures with various degrees of proliferation and atypia (Fig. 2, H&E).

Fig. 1

Small tubules are entrapped in sclero-elastotic stroma in the central nidus of a complex sclerosing lesion

Fig. 2

At the periphery of the nidus are radial structures formed by sclero-hyalinized stroma entrapping distorted tubular structures

CSL frequently involves papillomas leading to the diagnosis of “complex papillary sclerosing lesions” (CPSL). The sclero-hyalinazed tissue is predominant in such cases and areas of infiltrating epitheliosis (Usual Ductal Hyperplasia) may be frequently seen. In some cases of CSL, multiple foci of “adenosquamous proliferation” (ASP), often regarded as representing benign squamous metaplasia, are situated within the nidus and permeated between ducts beyond the corona of the CSL, with reactive hypercellular stroma. ASP may be related to infarction in the instance of papilloma or following previous fine needle- or CNBs (Wilsher et al. 2017). These ASPs have been considered as precursors of metaplastic carcinoma (Metaplastic Carcinoma) (Denley et al. 2000), in particular low grade adenosquamous carcinoma (Low Grade Adenosquamous Carcinoma), which are not a rare event in CSL (Tan et al. 2015).


Immunostains for myoepithelial markers (e.g., p63 or p40, calponin, smooth muscle myosin heavy chain, cytokeratin 5/6) may be helpful to distinguish entrapped benign tubules from a tubular carcinoma; however, in areas of sclero-hyalinosis, the myoepithelium may be very attenuated or even undetectable (Fig. 3, Immunostaining for p63). In analogy, basal cytokeratins (CK5/6, CK14) may not be just expressed at the periphery by basal/myoepithelial cells but also by luminal epithelial cells, particularly in cases associated with ASP (Fig. 4, Immunostaining for Cytokeratins 5/6).
Fig. 3

Immunostaining for p63 stains nuclei of myoepithelial cells. In some tubules only rare nuclei are evident

Fig. 4

Immunostaining for Cytokeratins 5/6 shows positivity of luminal epithelial cells in a focus of adenosquamous proliferation in a complex sclerosing lesion

Molecular Features

No specific molecular genetics of CSL have been described (Ellis and Simpson 2012).

PIK3CA mutations are present in 50–75% of sclerosing lesions (Wilsher et al. 2017). The mutation is a hallmark of ASP in CSL (Wilsher et al. 2017). Evidence suggests that radial scar/complex sclerosing lesions, sclerosing papilloma or similar lesions, are phenotypically similar to low-grade adenosquamous carcinoma (Low Grade Adenosquamous Carcinoma); their distinction is often subjective and is poorly defined in the literature.

Differential Diagnosis

On core biopsy, it may be difficult to distinguish the distorted glandular structures of CSL from invasive carcinoma. Therefore, biopsies should be reported with caution, using phrasing as “consistent with radial scar/complex sclerosing lesion,” also considering the frequency of additional pathology on excision. The differential diagnosis with tubular carcinoma (Tubular Carcinoma) has already been considered in the chapter “radial scar” (Radial Scar) demonstration of myoepithelial cells by immunohistochemistry is useful.

Gobbi et al. (2003) showed that distinction from metaplastic carcinomas (Metaplastic Carcinoma) arising in radial sclerosing lesions (RS, CSL, CPSL) and “pseudoinfiltrative glands” is often difficult and stressed that “to avoid overdiagnosis of malignancy in the reactive process, the lesion should present increased cellularity and clumps of cytokeratin positive plump spindle cells, besides the ‘reactive’ spindle cells and squamous elements”. It has also been stated that ductules of radial scars do not display a syringoid appearance (Ho et al. 2006).

References and Further Reading

  1. Denley, H., Pinder, S. E., Tan, P. H., Sim, C. S., Brown, R., Barker, T., Gearty, J., Elston, C. W., & Ellis, I. O. (2000). Metaplastic carcinoma of the breast arising within complex sclerosing lesion: A report of fivecases. Histopathology, 36, 203–209.CrossRefGoogle Scholar
  2. Ellis, I. O., & Simpson, J. F. (2012). Radial scar and complex sclerosing lesion. In S. R. Lakhani (Ed.), WHO classification of tumors of the breast (pp. 114–115). Lyon: IARC Press.Google Scholar
  3. Eusebi, V., & Millis, R. R. (2010). Epitheliosis, infiltrating epitheliosis, and radial scar. Seminar in Diagnostic Pathology, 27, 5–12.CrossRefGoogle Scholar
  4. Gobbi, H., Simpson, J. F., Jensen, R. A., Olson, S. J., & Page, D. L. (2003). Metaplastic spindle cell breast tumors arising within papillomas, complex sclerosing lesions, and nipple adenomas. Modern Pathology, 16, 893–901.CrossRefGoogle Scholar
  5. Hicks, D. G., & Lester, S. C. (2017). Diagnostic pathology: Breast (2nd ed.). Philadelphia: Elsevier.Google Scholar
  6. Ho, B. C., Tan, H. W., Lee, V. K., & Tan, P. H. (2006). Preoperative and intraoperative diagnosis of low-grade adenosquamous carcinoma of the breast: Potential diagnostic pitfalls. Histopathology, 49, 603–611.CrossRefGoogle Scholar
  7. Kennedy, M., Masterson, A. V., Kerin, M., & Flanagan, F. (2003). Pathology and clinical relevance of radial scars: A review. Journal of Clinical Pathology, 56, 721–724.CrossRefGoogle Scholar
  8. Nakhlis, F., Lester, S., Denison, C., Wong, S. M., Mongiu, A., & Golshan, M. (2018). Complex sclerosing lesions and radial sclerosing lesions on core needle biopsy: Low risk of carcinoma on excision in cases with clinical and imaging concordance. Breast Journal, 24, 133–138.CrossRefGoogle Scholar
  9. Patterson, J. A., Scott, M., Anderson, N., & Kirk, S. J. (2004). Radial scar, complex sclerosing lesion and risk of breast cancer. Analysis of 175 cases in Northern Ireland. European Journal of Surgical Oncology, 30, 1065–1068.CrossRefGoogle Scholar
  10. Racz, J. M., Carter, J. M., & Degnim, A. C. (2017). Challenging atypical breast lesions including flat epithelial atypia, radial scar, and Intraductal papilloma. Annals of Surgical Oncology, 24, 2842–2847.CrossRefGoogle Scholar
  11. Tan, Q. T., Chuwa, E. W., Chew, S. H., Lim-Tan, S. K., & Lim, S. H. (2015). Low-grade adenosquamous carcinoma of the breast: A diagnostic and clinical challenge. International Journal of Surgery, 19, 22–26.CrossRefGoogle Scholar
  12. Wilsher, M. J., Owens, T. W., & Allcock, R. J. (2017). Next generation sequencing of the nidus of early (adenosquamous proliferation rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic precursor lesion. Journal of Pathology: Clinical Research, 3, 115–122.PubMedGoogle Scholar

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Authors and Affiliations

  1. 1.Unit of PathologyCandiolo Cancer Institute FPO-IRCCSCandioloItaly
  2. 2.Department of Medical SciencesUniversity of TorinoTurinItaly