Journal of Cytology

: 2014  |  Volume : 31  |  Issue : 2  |  Page : 99--101

Cytological diagnosis of collagenous spherulosis of breast

Uday A Gokhale, Annu Nanda, G Rajasekharan Pillai 
 Department of Pathology, Sultan Qaboos Hospital, Salalah 211, Oman

Correspondence Address:
Annu Nanda
G 506, Somvihar, Sector 12, R K Puram, New Delhi - 110 022


Collagenous spherulosis is a rare entity usually seen in association with benign breast lesions. It is often picked up incidentally with a reported incidence of about 0.2% in cytological material. There are very few reports describing cytomorphological features of collagenous spherulosis. To the best of our knowledge this is the only case reported from the middle-east region. The presence of hyaline spherules surrounded by a single layer of benign myoepithelial cells is the hallmark of collagenous spherulosis on FNA. However, due to close cytological resemblance, it can be misdiagnosed as adenoid cystic carcinoma of the breast. A 40-year-old woman presented with a history of a painless lump in the infraareolar region of left breast for a year. Fine needle aspiration was performed. The smears showed scanty cellularity comprising of cohesive clusters and a few branching fragments of benign ductal epithelial cells closely intermingled with many spherical, acellular homogenous hyaline globules. Few bare bipolar nuclei were noted in the background. A diagnosis of collagenous spherulosis associated with benign proliferative breast disease was made. Cytopathologists need to be aware of this entity in order to differentiate it from adenoid cystic carcinoma of the breast which requires radical treatment.

How to cite this article:
Gokhale UA, Nanda A, Pillai G R. Cytological diagnosis of collagenous spherulosis of breast.J Cytol 2014;31:99-101

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Gokhale UA, Nanda A, Pillai G R. Cytological diagnosis of collagenous spherulosis of breast. J Cytol [serial online] 2014 [cited 2022 Dec 6 ];31:99-101
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Collagenous spherulosis of the breast was first described by Clement et al. [1] in 1987. It is a rare entity, which is encountered as an incidental microscopic finding in women in the third to fifth decade of life. It has been frequently seen in association with benign proliferative lesions of the breast, including sclerosing adenosis, radial scar, intraductal papilloma, fibroadenoma, adenomyoepithelioma, atypical ductal hyperplasia, etc. [2],[3]

The presence of hyalinized spherules may cause a diagnostic difficulty with malignant entities of breast like adenoid cystic carcinoma. [4] As collagenous spherulosis is an innocuous lesion not requiring any therapeutic intervention, it is of utmost importance to diagnose it correctly to avoid unnecessary treatment. [5] There have been very few reports in the English literature describing cytological features of collagenous spherulosis. [4],[5],[6],[7],[8],[9],[10],[11] We report a case of collagenous spherulosis detected by fine-needle aspiration cytology and discuss the cytomorphological findings to differentiate it from adenoid cystic carcinoma of the breast.

 Case Report

A 40-year-old woman presented with a history of a painless lump in the left breast for 1-year. On examination, a soft nodule measuring 1 cm × 1 cm was palpable in the left infraareolar region. The lump was subjected to fine-needle aspiration with a 22 G needle and a 20 mL syringe. Two attempts were made as the yield of the material was scanty. Air-dried smears were stained with May-Grünwald-Giemsa (MGG) stain and the ethanol fixed smears with Papanicolaou stain.

On microscopic examination, the smears showed cohesive clusters and a few branching fragments of benign ductal epithelial cells intimately mixed with many spherical, acellular homogeneous hyaline globules [Figure 1]. Many detached globules were also noted and a few globules showed laminar concentric layers lined by a single layer of uniform, small, oval or comma shaped cells [Figure 1]. A few dispersed bare, bipolar cells were also seen in the background with occasional fragments of adipose tissue. The color of these spherules was green in PAP stained smears and purplish-pink in MGG stained smears [Figure 2]. Periodic acid Schiff (PAS) stain showed strong positivity for these globules.{Figure 1}{Figure 2}

A diagnosis of collagenous spherulosis associated with benign proliferative breast disease was rendered. The case has not yet been biopsied, but no signs of progression have been observed on close clinical and mammographic follow-up of 1-year.


Collagenous spherulosis of the breast is a rare benign lesion with reported incidence of <1% in excisional specimens and about 0.2% in cytology material. [2],[6] The number of reported cases of collagenous spherulosis are few because of the lack of awareness of this entity among the cytopathologists and the limited volume of diagnostic cells and spherules in the aspirated material. [6] It may be encountered in both palpable as well as nonpalpable masses associated with other proliferative lesions. [1],[6] Although rare, it is a distinct entity with well-defined cytologic, microscopic, and ultrastructural features. [12]

Collagenous spherulosis is characterized by the presence of acellular, eosinophilic spherules varying 20-100 nm in size. [1] These spherules show a fibrillar structure either arranged in star shaped configuration or a laminar concentric appearance with central ring like structures or more commonly as hyalinized globules. [1] Some of the spherules may eventually calcify and are encountered as microcalcifications on mammography. [2] They are composed of abundant basement membrane material produced as a result of proliferation of myoepithelial cells. [12] The stimulus for its formation is unclear, but the association of collagenous spherulosis with fibrotic lesions suggests that localized fibrosis may serve as a promoting environment. [4]

Histochemically, these spherules are rich in collagen intravenous and basement membrane like proteoglycans such as heparan sulfate, laminin, and fibronectin. [5],[7] As a result they stain blue with trichrome, pinkish red with Van Gieson, black with reticulin and are variably positive with PAS and Alcian blue stains. [7] Immunohistochemical and ultrastructural studies confirm that the cells surrounding these spherules are myoepithelial in nature and are positive for cytokeratin, S-100 protein, actin, calponin, p63 and smooth muscle myosin. [13] A variant, designated as mucinous spherulosis, has also been described predominantly showing spherules composed of basophilic mucinous material and exhibiting similar immunohistochemical reactivity. [12]

The presence of hyaline globules, may lead to a misdiagnosis of adenoid cystic carcinoma, a rare salivary gland-like tumor of the breast. [4],[5] On cytology, monolayered clusters of cells with little branching architecture, cells with low nuclear/cytoplasmic ratio and a single layer of nuclei surrounding the spherules are seen, as noted in our case. In contrast, adenoid cystic carcinoma of the breast shows syncytial, multilayered, branching clusters of cells having high nuclear/cytoplasmic ratio and the spherules surrounded by several layers of cells. [6] The presence of bare, bipolar nuclei in the background points toward diagnosis of collagenous spherulosis. [5] However, there exists an overlap between the cytomorphological features of these two entities posing a diagnostic challenge to cytopathologists. [4],[14] In such difficult cases, it is advisable to recommend an open biopsy to make an accurate diagnosis. [12] Immunohistochemistry is also useful in differentiating these entities as smooth muscle myosin heavy chain and calponin are uniformly and strongly positive in collagenous spherulosis and negative in adenoid cystic carcinoma. C-kit (CD117) is a sensitive marker of adenoid cystic carcinoma, which is not expressed in collagenous spherulosis. [13]


Although, collagenous spherulosis is rarely reported in cytological smears yet the real incidence may be much more. It is necessary for cytopathologists to be aware of this innocuous lesion and avoid a false positive diagnosis of malignancy. A proper correlation with imaging modalities and clinical features is recommended with continued follow-up.


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