Encyclopedia of Pathology

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

Collagenous Spherulosis

  • Alena SkalovaEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-28845-1_4744-1

Synonyms

Definition

Collagenous spherulosis (CS) of the breast is a benign lesion most frequently associated with other benign proliferative processes, including papilloma, papillary duct hyperplasia, radial sclerosing lesions, sclerosing adenosis, and atypical ductal hyperplasia. Originally reported by Clement et al. in 1987, the lesion was first described as an incidental microscopic finding of intraluminal clusters of collagen-rich, eosinophilic, or star-shaped fibrillar spherules (Clement et al. 1987).

Clinical Features

  • Incidence: Collagenous spherulosis (CS) is very rare, with an estimated incidence of less than 1% in excisional specimens (Resetkova et al. 2006) and about 0.2% in cytology material (Sola Perez et al. 1993). CS may go unrecognized in about 48% of cases or may be misdiagnosed as atypical hyperplasia in 17% of cases or as in situ and/or invasive carcinoma in 11% of cases (Mooney et al. 1999).

  • Age and sex: The patients were all women ranging in age from 36 to 90 years (mean age, 52 years; median age, 50 years) in the largest published study (Resetkova et al. 2006).

  • Treatment and outcome: Although rare, CS is a distinct, morphologically well-defined entity most often reported in association with benign proliferative changes. Processes most frequently associated with collagenous spherulosis lesions include columnar cell hyperplasia, radial scar, sclerosing adenosis, papillomas, ductal hyperplasia without atypia, and adenomyoepithelioma (Reis-Filho et al. 2004). Less frequently, CS has been observed in specimens with a concurrent malignant process, most commonly lobular carcinoma in situ (LCIS) (Resetkova et al. 2006; Mooney et al. 1999). Association of CS with LCIS and other benign and malignant breast lesions is interpreted as most likely coincidental. CS could present as a mammographically suspicious mass or density and could be associated with microcalcifications. Treatment of the patient and clinical outcome of CS is dependent on accompanying breast lesion.

Macroscopy

CS is an incidental finding in breast samples removed for other reasons, and it is not visible at macroscopy.

Microscopy

CS is characterized by presence of eosinophilic intraluminal collagen-rich spherules measuring 20–100 μ in diameter, surrounded by flattened myoepithelial cells (Fig. 1 H&E). Most frequently, it shows a central floccular aggregate with radiating spikes that merge with the scalloped projections at the periphery. The material may also be finely granular and more evenly distributed in concentric onion skin-like pattern. The periphery of the sphere may be marked by an eosinophilic cuticle of variable thickness and staining intensity (Fig. 2 H&E). The hyaline material present within the intraluminal space is rich in collagen type IV of the basement membrane origin.
Fig. 1

Collagenous spherulosis (CS) associated with benign columnar cell hyperplasia

Fig. 2

The eosinophilic spherules of CS have a concentric fibrillary pattern with darker peripheral staining

Immunophenotype

The myoepithelial cells surrounding the basement membrane deposits in CS express myoepithelial markers, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin, p63 (Fig. 3a P63 immunostaining), and cytokeratin 14 (CK14) (Fig. 3b CK14 immunostaining).
Fig. 3

Immunostainings with p63 (a) and CK 14 (b) highlight myoepithelial cells, which form incomplete lining of the spherules

Differential Diagnosis

Cribriform architecture characterizes, in addition to CS, a broad spectrum of benign and malignant proliferations in the breast, chiefly invasive cribriform carcinoma, ductal carcinoma in situ, and adenoid cystic carcinoma (AdCC) (“Adenoid Cystic Carcinoma”). The differential diagnosis can be especially challenging in needle core biopsies (Rabban et al. 2006).

AdCC of the breast is a rare, special type of invasive breast carcinoma, accounting for 0.05–0.10% of all primary carcinomas of the breast. The myoepithelial immunophenotypic overlap between cribriform pattern AdCC of the breast and CS could lead to diagnostic pitfalls in evaluating cribriform lesions of the breast, especially in core needle biopsies. While smooth muscle actin and p63 are expressed by both entities, other myoepithelial markers, calponin and smooth muscle myosin heavy chain, are expressed only by CS and thus can be used to distinguish it from AdCC (Reis-Filho et al. 2004). In contrast, the staining for c-kit and EMA may facilitate identification of the ductules characteristic for AdCC.

References and Further Reading

  1. Clement, P. B., Young, R. H., & Azzopardi, J. G. (1987). Collagenous spherulosis of the breast. American Journal of Surgical Pathology, 11, 411–417.CrossRefGoogle Scholar
  2. Mooney, E. E., Kayani, N., & Tavassoli, F. A. (1999). Spherulosis of the breast. A spectrum of mucinous and collagenous lesions. Archives of Pathology & Laboratory Medicine, 123, 626–630.Google Scholar
  3. Rabban, J. T., Swain, R. S., Zaloudek, C. J., Chase, D. R., & Chen, Y. Y. (2006). Immunophenotypic overlap between adenoid cystic carcinoma and collagenous spherulosis of the breast: Potential diagnostic pitfalls using myoepithelial markers. Modern Pathology, 19, 1351–1357.CrossRefGoogle Scholar
  4. Reis-Filho, J. S., Fulford, L. G., Crebassa, B., et al. (2004). Collagenous spherulosis in an adenomyoepithelioma of the breast. Journal of Clinical Pathology, 57, 83–86.CrossRefGoogle Scholar
  5. Resetkova, E., Albarracin, C., & Sneige, N. (2006). Collagenous spherulosis of breast: Morphologic study of 59 cases and review of the literature. American Journal of Surgical Pathology, 30, 20–27.CrossRefGoogle Scholar
  6. Sola Perez, J., Perez-Guillermo, M., Bas Bernal, A., et al. (1993). Diagnosis of collagenous spherulosis of the breast by fine needle aspiration cytology: A report of two cases. Acta Cytologica, 37, 725–728.PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology, Faculty of Medicine in PlzenCharles UniversityPlzenCzech Republic
  2. 2.Biopticka laborator s.r.oPilsenCzech Republic