Spherulosis Research Articles

Collagenous spherulosis with lobular carcinoma in situ: a potential diagnostic pitfall

Sir,Collagenous spherulosis is a rare, benign breast lesion occurring in less than 1% of benign breast biopsies. Collagenous spherulosis was first described by Clement et al.1 as a lesion often see...

Cytological diagnosis of collagenous spherulosis of breast associated with fibroadenoma: Report of a case with review of literature

Collagenous spherulosis of the breast is a rare incidental finding frequently associated with other benign lesions of the breast. The estimated incidence of this innocuous condition is only about 0.2% in cytological material. It is of utmost importance to differentiate collagenous spherulosis from its malignant mimics to avoid unnecessary treatment. This article discusses the cytological findings of a case of collagenous spherulosis of breast associated with fibroadenoma, along with a brief review of literature.

A case of mucinous spherulosis of the breast diagnosed retrospectively in FNA material

We describe for the first time the cytologic features of mucinous spherulosis (MS), a variant of collagenous spherulosis (CS) of the breast characterized by cribiform structures containing lightly basophilic material, embedded in a loosely mucinous acellular background. Histologically, the lesion was part of a complex hyperplasia containing foci of sclerosing adenosis, and foci of atypical ductal hyperplasia (ADH). Immunohistochemical study showed reactivity with smooth muscle actin and focally for cytokeratin 14. Cytologic features of MS were recognized retrospectively and consisted of intermediate to large round hyaline spherules, naked or surrounded by myoepithelial cells. A fibrillary radial appearance was observed with Diff-Quick stain. We draw attention to the importance of recognizing these features because they can easily pose problems either by being overlooked or overdiagnosed as mucinous carcinoma. Differential diagnosis is briefly discussed.

The sclerosing variant of adenoid cystic carcinoma. A previously unrecognized neoplasm of major salivary glands

We report 2 cases of a previously unrecognized sclerosing variant of adenoid cystic carcinoma (ACC) of major salivary glands. One of the tumors arose in the parotid and the other in the submaxillary gland of young adult patients. The tumors were composed predominantly of varying-sized large sclerotic and hypocellular nodules containing myoepithelial cells and pseudovascular spaces, most likely the result of artifactual retraction. In moderately cellular nodules, there were numerous small globules or spherules surrounded by myoepithelial cells similar to those of collagenous or mucinous spherulosis. Focal cribriform areas and ductal structures lined by epithelial cells were also identified. Both tumors showed perineural invasion. Electron microscopy revealed that both large nodules and small globules or spherules were composed of excessive amounts of basement membrane and thick-banded collagen fibers. The myoepithelial cells showed immunoreactivity for smooth muscle actin (SMA), S100 protein, and vimentin. Collagen IV showed variable reactivity in both the large nodules and small spherules. More cases of the sclerosing variant of ACC and long-term follow-up of the patients are needed to determine the biologic behavior of this unusual but distinctive variant of ACC.

Collagenous Spherulosis of Breast

Collagenous spherulosis is a rare benign lesion that can microscopically mimic atypical ductal hyperplasia, cribriform ductal carcinoma in situ, or adenoid cystic carcinoma. Seventy-nine cases of collagenous spherulosis in women aged 36 to 90 years (mean age, 52 +/- 11 years) were identified from the University of Texas M. D. Anderson Cancer Center pathology files from the last 10 years. The pathology reports and slides from 59 patients were reviewed. This study does not attempt to evaluate the overall incidence of collagenous spherulosis because only cases with an actual diagnosis of collagenous spherulosis in pathology report were reviewed. The aim of this study was to investigate the underlying pathology within collagenous spherulosis and its relation to other pathologic findings within the specimen. Collagenous spherulosis was present as multiple foci ranging in size from 0.1 to 0.3 cm in 44 (75%) of the 59 cases. Collagenous spherulosis was associated with benign lesions of the breast in 41 cases, with atypical ductal hyperplasia in 3 cases, and with lobular carcinoma in situ in 15 cases. Microcalcifications were found in lesions involved by collagenous spherulosis in 15 cases. In summary, although collagenous spherulosis was mostly associated with benign breast lesions, in our study it was also frequently seen in association with lobular carcinoma in situ. Collagenous spherulosis could present as a mammographically suspicious mass or density and could be associated with microcalcifications. Increased numbers of cases of collagenous spherulosis may be expected in the future as a result of breast cancer-screening programs. Caution is needed not to overinterpret collagenous spherulosis as atypical or ductal carcinoma in situ, especially on core needle biopsy specimens.

Immunophenotypic overlap between adenoid cystic carcinoma and collagenous spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers

Adenoid cystic carcinoma of the breast is a rare neoplasm whose cribriform architecture may mimic invasive cribriform carcinoma, cribriform ductal carcinoma in situ, and collagenous spherulosis. The diagnosis may be even more challenging in needle core biopsies. Immunohistochemical expression of p63 and c-kit distinguishes adenoid cystic carcinoma from invasive cribriform carcinoma and ductal carcinoma in situ. A formal comparison of the immunophenotype of adenoid cystic carcinoma to collagenous spherulosis has not been reported. Of concern is the overlap in myoepithelial markers between these two entities. Both may express S100, smooth muscle actin, and p63. This overlap may cause diagnostic confusion yet is under-emphasized in the literature. The expression profile of newer myoepithelial markers has not been studied in this setting. We evaluated smooth muscle actin, p63, calponin, smooth muscle myosin heavy chain, as well as c-kit, in nine cases of cribriform pattern adenoid cystic carcinoma of the breast in comparison to 12 cases of collagenous spherulosis. Both entities strongly expressed p63 and smooth muscle actin; in adenoid cystic carcinoma, the basaloid myoepithelial-like tumor cells expressed these markers, but the ductular epithelial cells did not. Neither calponin nor smooth muscle myosin heavy chain was expressed in adenoid cystic carcinoma but both were strongly expressed in collagenous spherulosis. Whereas the ductular epithelial cells of adenoid cystic carcinoma were positive for c-kit in all cases, collagenous spherulosis was negative for c-kit. Positive p63 expression by a cribriform breast lesion is not sufficiently specific to confirm a diagnosis of adenoid cystic carcinoma. A broader panel that includes calponin or smooth muscle myosin heavy chain and c-kit is required to exclude collagenous spherulosis in settings in which the distinctive morphologic features that separate these entities are not conspicuously present. Reliance on p63 or smooth muscle actin alone poses a potential diagnostic pitfall in evaluating cribriform breast lesions.

Urothelial Signet-Ring Cell Carcinoma of the Renal Pelvis with Collagenous Spherulosis: A Case Report

We present a unique case of urothelial carcinoma of the right renal pelvis. It occurred in a 58-year-old woman. The tumor was located in the renal pelvis with extension into the adjacent renal medulla and cortex. Two years after surgical excision the patient is free of recurrence and metastasis. The tumor was well demarcated, without capsule, firm, solid, and whitish on the cut surface. It was 3x4 cm in largest diameter and without signs of necroses and hemorrhages. The tumor did not infiltrate the ureter. Histologically the predominant pattern of the tumor was adenocarcinomatous differentiation, and only very rare foci of urothelial carcinoma composed of typical transitional cells were found. No signs of intestinal type of metaplasia and adenocarcinoma, changes similar to the cystitis cystica or cystitis glandularis, were found in the tumor or in its vicinity. Most of the tumor looked like solid nests composed of cells with intracytoplasmic lumens. The resulting appearance was that of typical signet-ring cell change. These solid nests were usually surrounded by columnar epithelium, which in many areas formed papillary structures. A very striking feature was formation of collagen spherules. Small collagen spherules were often surrounded by a layer of the neoplastic cells so that collagenous rosettes were formed. In some areas these collagenous spherules clustered together so that they formed areas of collagenous spherulosis. The collagen in the spherules reacted positively with collagen IV. Ultrastructurally these spherules were formed by basal membrane-like material. Intracytoplasmic lumens of the signet-ring cell change were endowed by slender microvilli at ultrastructural level.

Observations on the Pathologic Diagnosis of Selected Unusual Lesions in Needle Core Biopsies of Breast

Pathologic diagnoses rendered on needle core biopsies of mammary lesions are primary determinants of further intervention. Such biopsies are being performed for an ever-widening range of diseases in an attempt to reliably and efficiently render a diagnosis. This review is intended to provide practical guidance to pathologists in dealing with selected unusual lesions encountered in these biopsies. Herein we offer advice on avoiding common diagnostic errors and on considering the relevant differential diagnosis of mucocele-like lesions, spindle-cell metaplastic carcinoma, adenomyoepithelioma, pseudoangiomatous stromal hyperplasia (PASH), collagenous spherulosis, myofibroblastoma, vascular lesions, and lymphoid infiltrates in the breast.

Criteria for the Diagnosis of Fibroepithelial Lesions of the Breast with Liquid-Based Cytology

To establish diagnostic criteria for diagnosing and differentiating fibroepithelial lesions of the breast on ThinPrep (Cytyc Corp., Boxborough, Massachusetts, U.S.A.).Eighty-four fibroepithelial lesions were sampled by ultrasound-guided aspiration biopsy. Based on smears and histologic correlates, there were 55 fibroadenomas, 26 papillary neoplasms and 3 phyllodes tumors. The ThinPrep slides for each sample were reviewed retrospectively and evaluated for specific morphologic and cytologic features.On ThinPrep slides, 95% of the fibroadenomas had a predominance of single myoepithelial nuclei, 89% had staghorn clusters, and 47% had myxoid stroma. Among the papillary neoplasms, 8% had a predominance of single columnar ductal cells, 31% had papillary groups, 23% had vessels, and 27% had collagenous spherulosis. The ThinPrep preparations of the phyllodes tumors showed that 67% had single myoepithelial nuclei, 33% had a predominance of single ductal cells, 67% had staghorn clusters, and 0% had myxoid stroma. A majority of the fibroadenomas and the papillary neoplasms showed mild to moderate ductal epithelial hyperplasia. A majority of the phyllodes tumors showed moderate ductal epithelial hyperplasia.Fibroepithelial lesions of the breast can be accurately differentiated using ThinPrep samples based on the evaluation of specific cytologic and morphologic features, including the presence of staghorn clusters, fibromyxoid stroma, vessels, collagenous spherulosis, papillary clusters and predominance of myoepithelial nuclei or columnar cells in the background. However, the degree of ductal epithelial hyperplasia does not aid in the diagnosis.

Extracellular Hyaline Material in Association with Other Cytologic Features in Aspirates from Collagenous Spherulosis and Adenoid Cystic Carcinoma of the Breast

To reevaluate breast aspirates showing extracellular hyaline material (EHM) and globules to assess if clinicoradiologic and cytologic features could help in differentiating between benign and malignant lesions, especially collagenous spherulosis (CS) and adenoid cystic carcinoma (ACC). Fine needle aspiration was performed on 884 patients with breast lumps. The cytomorphologic features of 6 cases showing EHM, including classic hyaline globules (HGs), were analyzed in detail. Three cases also had hemorrhagic nipple discharge. Tissue diagnosis (4) and mammography (6) were available. Aspirate smears revealed high cellularity composed of monolayers: clusters of uniform, small cells; EHM; and HGs surrounded by similar cells. Benign naked nuclei and stromal fragments (4), nuclear pleomorphism (3), apocrine cells (2), foam cells (2), naked HGs (2) and spindle cells in proximity to HGs were also seen (4). Nipple discharge smears showed foam cells, erythrocytes (3) and epithelial cell clusters with hyaline material (1). The cytologic diagnosis was CS (4) and ACC (2). Histopathology confirmed the diagnosis of CS (2) and ACC (1). There may be a morphologic overlap between the cytomorphologic features of CS and ACC, leading to diagnostic errors. The presence of EHM and HGs in association with bland cellular features should be interpreted with caution to avoid erroneous diagnoses. Histopathology is mandatory in these cases because of their different prognostic implications.

Cytology of collagenous spherulosis of the breast: a diagnostic dilemma--report of three cases.

Collagenous spherulosis is a rare incidental finding seen in association with benign breast lesions. Cytological findings in three cases of collagenous spherulosis diagnosed on fine needle aspiration are presented. The presence of hyaline pink globules surrounded by benign myoepithelial cells in Giemsa stained smears was a diagnostic feature. Associated lesions were atypical papillary hyperplasia (2) and fibroadenoma (1). Adenoid cystic carcinoma was the close differential diagnosis on cytology. Awareness of this entity is important to avoid a false positive diagnosis of malignancy.

Complex Collagenous Spherulosis of the Breast Presenting as a Palpable Mass: A Case Report with Immunohistochemical and Ultrastructural Studies.

Collagenous spherulosis is a rare, benign breast lesion occuring in less than 1% of benign breast biopsies. All previously reported cases have been discovered as incidental microscopic findings in association with a range of benign to malignant processes. The authors report the first case of collagenous spherulosis presenting as a palpable mass. Immunohistochemistry and electron microscopy performed on this lesion demonstrated the presence of two cell types: epithelial cells and myoepithelial cells with associated basement membranelike material. Collagenous spherulosis may mimic adenoid cystic carcinoma since the epithelial proliferation and spherule formation in collagenous spherulosis closely resembles the changes in adenoid cystic carcinoma. However, adenoid cystic carcinoma is an invasive lesion that is almost always palpable, while collagenous spherulosis is almost always an incidental microscopic finding. Our case illustrates that collagenous spherulosis can also result in a palpable mass, thus palpability of the lesion cannot be used to differentiate these conditions.

Collagenous spherulosis versus shadow cell differentiation in endometrioid adenocarcinoma

Collagenous spherulosis versus shadow cell differentiation in endometrioid adenocarcinoma

Uncommon morphologic patterns of lobular neoplasia.

Discussions of the morphology of lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in-situ) usually emphasize the commonplace characteristics. Occasional cases deviate from the expected appearance and thereby cause diagnostic confusion. Unusual cytologic alterations include the formation of signet-ring cells and the presence of nuclear pleomorphism. The growth of lobular neoplasia in breast tissue altered by atrophy, sclerosing adenosis, collagenous spherulosis, and benign tumors gives rise to unexpected patterns that one might mistake for normal tissue, invasive carcinoma, or ductal carcinoma in situ. Solid involvement of ducts by lobular neoplasia and uncommon forms of "pagetoid" growth both resemble the appearance of atypical ductal hyperplasia or ductal carcinoma in situ. The authors illustrate these unusual cytologic and architectural findings and discuss features that permit proper diagnosis and interpretation.

Spherulosis of the Breast

Abstract Objective.—Collagenous spherulosis of the breast is an uncommon localized pattern of basement membrane material deposition that may be mistaken for atypical proliferations or carcinoma. This report describes 9 cases in which the predominant or exclusive appearance of the spherules was basophilic instead of eosinophilic. Design.—The files of all cases of collagenous spherulosis diagnosed at the Armed Forces Institute of Pathology were reviewed to ascertain the frequency of diagnosis. Results.—Spherulosis with a predominantly basophilic pattern had a histochemical and immunohistochemical profile similar to collagenous spherulosis and was associated with more collagenous-appearing forms in 7 of 9 cases. Review of 81 cases showed that collagenous spherulosis was correctly diagnosed in 15% of referrals and was mistaken for intraductal or invasive carcinoma in 11% of cases. Conclusions.—Mucinous and collagenous patterns appear to be related forms of spherulosis. They are underrecognized by pathologists...

Spherulosis of the breast. A spectrum of municous and collagenous lesions.

Collagenous spherulosis of the breast is an uncommon localized pattern of basement membrane material deposition that may be mistaken for atypical proliferations or carcinoma. This report describes 9 cases in which the predominant or exclusive appearance of the spherules was basophilic instead of eosinophilic. The files of all cases of collagenous spherulosis diagnosed at the Armed Forces Institute of Pathology were reviewed to ascertain the frequency of diagnosis. Spherulosis with a predominantly basophilic pattern had a histochemical and immunohistochemical profile similar to collagenous spherulosis and was associated with more collagenous-appearing forms in 7 of 9 cases. Review of 81 cases showed that collagenous spherulosis was correctly diagnosed in 15% of referrals and was mistaken for intraductal or invasive carcinoma in 11% of cases. Mucinous and collagenous patterns appear to be related forms of spherulosis. They are underrecognized by pathologists and maybe mistaken for atypia or malignancy.

Spherulosis of the Breast

Abstract Objective.—Collagenous spherulosis of the breast is an uncommon localized pattern of basement membrane material deposition that may be mistaken for atypical proliferations or carcinoma. This report describes 9 cases in which the predominant or exclusive appearance of the spherules was basophilic instead of eosinophilic. Design.—The files of all cases of collagenous spherulosis diagnosed at the Armed Forces Institute of Pathology were reviewed to ascertain the frequency of diagnosis. Results.—Spherulosis with a predominantly basophilic pattern had a histochemical and immunohistochemical profile similar to collagenous spherulosis and was associated with more collagenous-appearing forms in 7 of 9 cases. Review of 81 cases showed that collagenous spherulosis was correctly diagnosed in 15% of referrals and was mistaken for intraductal or invasive carcinoma in 11% of cases. Conclusions.—Mucinous and collagenous patterns appear to be related forms of spherulosis. They are underrecognized by pathologists and maybe mistaken for atypia or malignancy.

What makes collagenous spherulosis?

What makes collagenous spherulosis?

Collagenous Spherulosis: An Ultrastructural Study

Ultrastructural findings are described in two cases of collagenous spherulosis associated with intraductal hyperplasia and sclerosing adenosis. The spherules showed a variable composition of basement membrane, banded collagen, and mineral deposition. Some spherules were connected to the periacinal stroma by a thin pedicle. The authors propose that spherules represent a peculiar form of stromal invagination that could be seen in a variety of breast lesions, rather than a form of intraductal hyperplasia.

Diagnostic Pitfalls in Aspiration Biopsy Cytology of Papillary Breast Lesions.

Our experience with 12 papillary breast lesions included eight intraductal papillomas, three primary papillary carcinomas, and one metastatic papillary ovarian carcinoma. Five of the eight intraductal papillomas displayed diagnostic findings including tridimensional papillary fragments of ductal cells with distended cytoplasmic vacoules and dense scalloped cytoplasm. Three intraductal papillomas displayed cohesive fragments containing epithelial cells surrounding metachromatic, globoid, and cylindrical structures that were bright red following Diff-Quik staining and pale blue following Papanicolaou staining. Such unusual findings may raise the differential diagnoses of adenoid cystic carcinoma and collagenous spherulosis. However, the metachromatic material of intraductal papilloma represents type-I collagen-rich stroma of hyalinized fibrovascular stalks, while the material of adenoid cystic carcinoma and collagenous spherulosis represents type-IV collagen. Two of the three primary papillary carcinomas displayed cytologic findings similar to those of intraductal papillomas except for increased anisonucleosis and cell dyshesion, while the third displayed innumerable psammoma bodies similar to the metastatic ovarian carcinoma.