Spherulosis Research Articles

Immunohistochemical marker profiles for the differentiation of collagenous spherulosis from adenoid cystic carcinoma of the breast

Collagenous spherulosis (CS) is a rare breast lesion of unknown histogenesis. Adenoid cystic carcinoma (ACC) is a rare basal-like breast carcinoma with low histological grade. CS is a benign lesion but resembles ACC. Both lesions show a similar histomorphology and feature bilineage differentiation. This study compared immunohistochemical markers in CS and ACC.We compiled n = 13 CS cases and n = 18 mammary ACCs. Fourteen marker proteins (ER, PR, HER2, GATA3, CK7, E-cadherin, CD117, CK5/14, p40, p63, SMA, CD10, calponin, P-cadherin) were evaluated by immunohistochemistry (IHC). MYB rearrangement, a common alteration in ACC, was assessed by fluorescence in situ hybridization.Patient age ranged between 40-60 years for CS lesions and 30–90 years for ACCs. 7/13 (54%) CS cases harbored a lobular carcinoma in situ (LCIS) in the luminal component. One CS/LCIS lesion occurred in a carrier of a pathogenic germline variant in CDH1/E-cadherin. MYB rearrangement was detected in 0/11 (0%) CS and 6/16 (37%) ACC cases (P = 0.054). CS was associated with expression of ER in the luminal component (P < 0.001), E-cadherin loss in the luminal component (P = 0.045), and expression of CD10 and calponin in the basal component (P < 0.001). Furthermore, CS was associated with GATA3 expression in the luminal component (12/13 [92%] versus 5/18 [27%], P < 0.001).In summary, IHC for GATA3 and E-cadherin may contribute to the differential diagnosis between CS and ACC, although these markers are not exclusively expressed in either lesion. Histologic evaluation has to take into account that CS is frequently colonized by LCIS, requiring thorough correlation of histomorphology and immunohistochemical features.

Collagenous Spherulosis Presenting as Architectural Distortion on Mammography.

Collagenous Spherulosis Presenting as Architectural Distortion on Mammography.

Sifter and Mesh-Cribriform Carcinoma Breast

Invasive cribriform carcinoma breast emerges as a low grade subtype of invasive carcinoma breast. Neoplasm preponderantly (&gt;90%) delineates a pure cribriform architecture or may represent as a mixed tumour composed of 10% to 90% of variant morphological subtype. Tumefaction is constituted of islands or nests of malignant epithelial cells demonstrating spherical or angulated contours or configure well defined cribriform spaces articulated by arches of epithelial cells, thereby delineating a sieve-like appearance with intercellular lumens impregnated with secretions. Miniature tumour cells display mild to moderate pleomorphism with absent nuclear atypia. Cribriform carcinoma breast is immune reactive to Oestrogen receptors(ER) or progesterone receptors (PR) and immune non-reactive to HER2 or diverse myoepithelial markers. Cribriform carcinoma breast requires segregation from neoplasms as adenoid cystic carcinoma, cribriform variant of ductal carcinoma in situ, collagenous spherulosis, well differentiated neuroendocrine tumour or well differentiated invasive breast cancer of no special type (NST). Neoplasm may be appropriately ascertained by mammography or ultrasonography of the breast. Cribriform carcinoma breast may be appropriately alleviated by primary surgical eradication of the lesion.

Usual breast lump with unusual features.

The co-existence of granulomatous mastitis and collagenous spherulosis in a breast lump is an uncommon finding. The awareness of cytomorphological features can help corroborate a cytological diagnosis. A palpable breast lump in an elderly female warrants urgent attention and fine needle aspiration is a rapid, reliable method of evaluation. An elderly female with a firm breast lump mimicking malignancy was subjected to fine needle aspiration cytology (FNAC). Smears showed ill-formed granulomas, inflammatory cells and homogeneous hyaline stromal globular elements intermingled with the benign ductal epithelial and myoepithelial cells.

MYB RNA In Situ Hybridization Is a Useful Diagnostic Tool to Distinguish Breast Adenoid Cystic Carcinoma From Other Triple-negative Breast Carcinomas.

Breast adenoid cystic carcinoma (AdCC) has overlapping features with basal-like triple-negative breast carcinoma (TNBC), yet carries a more favorable prognosis, and accurate diagnosis is critical. Like salivary gland AdCC, breast AdCC demonstrates recurrent alterations in the MYB gene. Novel chromogenic RNA in situ hybridization (ISH) for MYB has emerged as sensitive and specific for salivary gland AdCC. Here, we evaluate MYB RNA ISH in invasive ductal carcinomas (IDCs) including basal-like TNBC, and in the histologic mimics ductal carcinoma in situ (DCIS) and collagenous spherulosis. MYB RNA ISH was also performed on previously constructed tissue microarrays containing 78 evaluable IDC, including 30 basal-like TNBC (EGFR+ and/or CK5/6+), 19 luminal A (ER+/HER-2-), 12 HER-2+ (ER-/HER-2+), 11 non-basal-like TNBC, and 6 luminal B (ER+/HER-2+). MYB RNA ISH overexpression was seen in 100% (n=18/18) of primary breast AdCC and 10% (n=8/78) of IDC (P<0.0001). MYB RNA ISH was overexpressed in 37% (n=7/19) of luminal A and 8% (n=1/12) of HER-2+ IDC, and in no cases of TNBC or luminal B IDC. The majority (67%, n=8/12) of DCIS and all (n=7) cases of collagenous spherulosis demonstrated overexpression of MYB RNA. MYB gene rearrangement was detected in 67% (n=4/6) evaluable AdCC. Although MYB RNA ISH overexpression cannot be used to distinguish between cribriform DCIS or collagenous spherulosis and AdCC, MYB RNA ISH is absent in basal-like TNBC and rare in ER+ or HER-2+ IDC. MYB RNA ISH could be a useful, sensitive, and rapid diagnostic adjunct in the workup of a triple-negative carcinoma in the breast.

Collagenous Spherulosis of Breast Diagnosed on Cytology: A Case Report

Collagenous Spherulosis of Breast Diagnosed on Cytology: A Case Report

Collagenous Spherulosis Associated with Lobular Carcinoma In Situ of the Breast: Two Case Reports.

Collagenous Spherulosis Associated with Lobular Carcinoma In Situ of the Breast: Two Case Reports.

Pathologic Spectrum of Secretory and Mucinous Breast Lesions

-The morphologic spectrum of secretory breast lesions encompasses benign, borderline, and malignant lesions. They are characterized by luminal pink, proteinaceous secretions and variable degrees of cytologic atypia ranging from low grade to high grade, with frequent papillary formations. Other lesions, benign and malignant, can also show luminal and extraluminal secretions and share similar features with secretory lesions, making them diagnostically challenging. -To discuss the differential diagnosis of secretory breast lesions, emphasizing the most important diagnostic features of benign and malignant lesions. Lesions with intraluminal secretions discussed at length in this review include pregnancy-like hyperplasia, cystic hypersecretory hyperplasia, collagenous spherulosis, microglandular adenosis, hypersecretory carcinoma, and secretory carcinoma. Lesions with extravasated mucin, such as mucocele-like lesions and mucinous carcinoma, are also briefly discussed. -Published articles obtained from a PubMed search of the English literature were the primary source for this review. -Lesions with secretory features described in this review show a pathologic spectrum, sometimes even within the same lesion. As a consequence, one should employ a low threshold for recommending reexcision on a core biopsy containing benign-appearing hypersecretory glands and use all ancillary data, including clinical presentation, imaging findings, morphology, immunohistochemistry, and molecular pathology, to render a final diagnosis.

The unique luminal staining pattern of cytokeratin 5/6 in adenoid cystic carcinoma of the breast may aid in differentiating it from its mimickers.

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n=14) and in collagenous spherulosis (n=5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1-specificity) at threshold settings of 0, 10, 50, and 70%. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.

Clinicopathologic features of collagenous spherulosis of the breast

To investigate the morphological features, immunohistochemical phenotype, diagnosis and differential diagnosis of collagenous spherulosis of the breast. Clinicopathologic observation, immunohistochemistry using EnVision method and histochemical staining were applied in 33 cases of collagenous spherulosis of the breast. Collagenous spherulosis of the breast was a benign lesion, consisting of proliferative myoepithelial and ductal epithelial cells. These cells were arranged in a cribriform pattern with esinophilic, round, oval or star-shaped fibrillary spherules in the lumen.SMA, calponin and p63 by immunohistochemistry identified the proliferative myoepithelium, while E-cadherin identified the proliferative ductal epithelial cells. The esinophilic spherules were stained with collagen type IV, AB-PAS and reticulin. Collagenous spherulosis was often found in sclerosing adenosis. Collagenous spherulosis of the breast is often associated with other diseases. It has special morphological presentation and is easily confused with malignant tumors such as adenoid cystic carcinoma or cribriform carcinoma in situ, and needs to be differentiated from these disease entities.

CD10 and HHF35 actin in the differential diagnosis between Collagenous Spherulosis and Adenoid-Cystic Carcinoma of the breast

Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions.We performed an immmunohistochemical study on 6 cases of CS and 9 cases of AdCC.We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both.Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR−, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35− immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit−) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity.Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.

In situ lobular neoplasia of the breast with marked myoepithelial proliferation

To present four new cases of in situ lobular neoplasia associated with marked proliferation of myoepithelial cells. Four recently seen cases showing extensive foci of in situ lobular neoplasia, as confirmed by negative E-cadherin staining, were stained for myoepithelial cells using CD10, smooth muscle actin and cytokeratin 5/6. Invasive lobular carcinoma was also present in two cases; one case was associated with multiple foci of collagenous spherulosis, and one was associated with a radial scar. Marked myoepithelial proliferation was seen around most of the in situ lobular foci or mingled with lobular cells. Marked proliferation of myoepithelial cells is sometimes encountered in association with extensive in situ lobular neoplasia. It is suggested that this proliferation might have a role in maintaining the in situ status of these lesions or, alternatively, that there is a shared factor responsible for the simultaneous proliferation of certain 'lobular' cell types and myoepithelial cells.

Significance of collagenous and mucinous spherulosis in breast cytology specimens

Spherulosis of the breast is a rare but distinct benign morphological entity. As there are few cytological reports of breast spherulosis, the significance of spherulosis among cytological specimens is unclear. The objective was to document cytological aspects of spherulosis. A total of 3491 consecutive breast fine needle aspiration cytology (FNAC) samples and 69 nipple discharge cytology samples were reviewed. Papanicolaou-stained slides with or without Romanowsky staining were analysed. The corresponding 1926 histological specimens were also reviewed. We detected 17 cases of collagenous spherulosis (CS) and/or mucinous spherulosis (MS) among 3560 breast cytology specimens (0.48%). All samples were from women, who varied in age from 22 to 69 years. CS and/or MS were present in 15 of 3491 FNAC specimens (0.43%) and in two of 69 nipple discharge cytology specimens (2.9%). Corresponding histological specimens were available for 14 of the 17 specimens. Of the 14 specimens, 12 consisted of intraductal papilloma, one of fibroadenoma, and one of fibrocystic change. There was no spherulosis among the 1251 cytological specimens of malignant diseases. Cytological evidence of spherulosis is a good indicator of intraductal papilloma.

Adenoid cystic carcinoma of breast and the importance of differentiation from collagenous spherulosis by FNAC

We are presenting a case of adenoid cystic carcinoma (ACC) of breast in a 66-year-old woman having lump in left breast, admitted to surgical ward of our institute. A diagnosis of ACC of breast was made and subsequently confirmed histopathologically and on immunohistochemistry.

Collagenous Spherulosis Presenting as a Mass Lesion on Imaging

Collagenous Spherulosis Presenting as a Mass Lesion on Imaging

Collagenous spherulosis in an oral mucous cyst

Collagenous spherulosis is a histological pattern that has been described in both benign and malignant salivary gland tumors, proliferative lesions of breast ductal epithelium, chondroid syringomas and schwannomas. Histologic structures of similar appearance have also been reported in oral extravasation mucoceles as questionable myxoglobulosis or myxoglobulosis-like change. We report collagenous spherulosis within a mucocele removed from the lower lip of a 17-year-old female. Based upon histologic appearance, immunophenotypic data and review of the literature, we hypothesize that collagenous spherulosis and myxoglobulosis are morphologically related reaction patterns.

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

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

Adenoid cystic variant of papillary thyroid carcinoma: A case report with fine‐needle aspiration cytology

Diagnostic CytopathologyVolume 36, Issue 1 p. 64-66 Letter to the EditorFree Access Adenoid cystic variant of papillary thyroid carcinoma: A case report with fine-needle aspiration cytology Hüseyin Üstün M.D., M.I.A.C., Hüseyin Üstün M.D., M.I.A.C. Department of Pathology, Ankara Training and Research Hospital, Ankara, TurkeySearch for more papers by this authorFatma Öz Atalay M.D., Corresponding Author Fatma Öz Atalay M.D. [email protected] Department of Pathology, Ankara Training and Research Hospital, Ankara, TurkeyKultur Mah, Atac–2 Sok, No. 72/6, Kizilay, Ankara 06420, TurkeySearch for more papers by this authorCemil Ekinci M.D., Cemil Ekinci M.D. Department of Pathology, Faculty of Medicine, Ankara University, Ankara, TurkeySearch for more papers by this author Hüseyin Üstün M.D., M.I.A.C., Hüseyin Üstün M.D., M.I.A.C. Department of Pathology, Ankara Training and Research Hospital, Ankara, TurkeySearch for more papers by this authorFatma Öz Atalay M.D., Corresponding Author Fatma Öz Atalay M.D. [email protected] Department of Pathology, Ankara Training and Research Hospital, Ankara, TurkeyKultur Mah, Atac–2 Sok, No. 72/6, Kizilay, Ankara 06420, TurkeySearch for more papers by this authorCemil Ekinci M.D., Cemil Ekinci M.D. Department of Pathology, Faculty of Medicine, Ankara University, Ankara, TurkeySearch for more papers by this author First published: 06 December 2007 https://doi.org/10.1002/dc.20716Citations: 5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. References 1 DeLellis RA,Lloyd RV,Heitz PU,Eng C. Pathology and genetics of tumours of endocrine organs. Lyon: IARC Press; 2004. p 57– 66. 2 Haji BE,Ahmed MS,Prasad A,Omar MS,Das DK. Papillary thyroid carcinoma with an adenoid cystic pattern. Report of a case with fine-needle aspiration cytology and immunocytochemistry. Diagn Cytopathol 2004; 30: 418– 421. 3 Nguyen GK,Vogelsang PJ,Schumann GB. Follicular carcinoma of thyroid with an adenoid cystic pattern. Acta Cytol 1993; 37: 740– 744. 4 Yamazaki K. Unique follicular carcinoma of the thyroid gland with extracellular deposition of amorphous globular structures mimicking an adenoid cystic pattern. Virchows Arch 2003; 443: 690– 692. 5 El Hag IA,Kollur SM. Benign follicular thyroid lesions versus follicular variant of papillary carcinoma: Differentiation by architectural pattern. Cytopathology 2004; 15: 200– 205. 6 Jogai S,Adesina AO,Temim L,Al-Jassar A,Amanguno HG. Follicular variant of papillary thyroid carcinoma—A cytological study. Cytopathology 2004; 15: 212– 216. 7 Das DK.Malik MK,Scharma P, et al. Papillary thyroid carcinoma and its variants in fine needle aspiration smears. Acta Cytol 2004; 48: 325– 336. 8 Natarjan S,Greaves TS,Raza AS,Cobb CJ. Fine-needle aspiration of an adenoid cystic carcinoma of the larynx mimicking a thyroid mass. Diagn Cytopathol 2004; 30: 115– 118. 9 Van der Wall JE,Becking AG,Snow GB,van der Waal I. Distant metastasis of adenoid cystic carcinoma of salivary glands and the value of diagnostic examinations during follw-up. Head Neck 2002; 24: 779– 783. 10 Highland KE,Finley JL,Neill JSA,Silverman JF. Collagenous spherulosis: Report of a case with diagnosis by fine needle aspiration biopsy with immunocytochemical and ultrastructural observations. Acta Cytol 1993; 37: 3– 9. 11 Jain S,Kumar N,Sodhani P,Gupta S. Cytology of spherulosis of the breast: A diagnostic dilemma—Report of three cases. Cytopathology 2002; 13: 116– 120. 12 Jain S,Gupta S,Kumar N,Sodhani P. Extracellular hyaline material in assosiation with other cytologic features in aspirates from collagenous spherulosis of the breast and adenoid cystic carcinoma of the breast. Acta Cytol 2003; 47: 381– 386. 13 Ogata K,Sakamato G,Sakurai T. Adenoid cystic carcinoma with collagenous spherulosis-like structures in the breast. Report of a case. Pathol Int 2004; 54: 332– 336. Citing Literature Volume36, Issue1January 2008Pages 64-66 ReferencesRelatedInformation

Apocrine mixed tumor of the skin (“mixed tumor of the folliculosebaceous-apocrine complex”): Spectrum of differentiations and metaplastic changes in the epithelial, myoepithelial, and stromal components based on a histopathologic study of 244 cases

A systematic analysis of the entire spectrum of various forms of differentiation and metaplastic epiphenomena in cutaneous apocrine mixed tumor (AMT) has never been performed. The purpose of our study was to study a large number of cutaneous mixed tumors so as to fully characterize the entire spectrum of differentiations and metaplastic changes that may occur in the epithelial, myoepithelial, and stromal components of AMT. This article reports a light-microscopic study of 244 cases of cutaneous AMT, complemented by a literature review. All types of differentiation along the lines of the folliculosebaceous-apocrine unit can be seen in AMT. The spectrum of metaplastic changes in the epithelial components includes squamous metaplasia, mucinous metaplasia, oxyphilic metaplasia, clear cell change, columnar metaplasia, hobnail metaplasia, and cytoplasmic vacuolization. The following changes in the myoepithelial component were documented: clear cell change, hyaline cells, plasmacytoid cells, spindling, and collagenous spherulosis. Stromal alterations included chondroid metaplasia, osseous metaplasia, and adipose metaplasia. This study utilizes tissue specimens that mainly came as consultations; therefore some inherent selection bias exists. AMT displays a wide range of differentiation and metaplastic changes in its epithelial, myoepithelial, and stromal components. These phenomena are not mutually exclusive. When unduly prominent, they may present diagnostic pitfalls. Our findings corroborate those of previous publications, stressing the remarkable diversity of differentiation and metaplasias that may be found in cutaneous AMT. We propose that the most appropriate name for these lesions is "mixed tumor of the folliculosebaceous-apocrine complex."

Collagen‐rich variant of benign epithelioid peripheral nerve sheath tumor of the skin

Schwannoma and neurofibroma account for the majority of cutaneous benign peripheral nerve sheath tumors and usually pose little diagnostic difficulty in their classic forms. In rare instances, however, benign peripheral nerve sheath tumors may display epithelioid morphology and lack otherwise usual features of schwannoma or neurofibroma, making classification difficult. These unusual changes may prompt consideration of other benign neoplasms or a malignancy. Benign epithelioid peripheral nerve sheath tumor (BEPNST) is a somewhat non-specific term recently proposed to describe these neoplasms of imprecise histogenesis. Also diagnostically challenging, rare BEPNST with unusual arrangements of extracellular collagen have been described and reported as neuroblastoma-like schwannoma and collagenous spherulosis. We report a unique case of cutaneous BEPNST with a peculiar arrangement of abundant extracellular collagen, different than the previously observed patterns. Specifically, the neoplastic cells in this tumor were nearly obscured by the collagen, which formed large nodules and compressed the majority of the few remaining tumor cells to the periphery of the lesion. This excessive collagen production emphasizes the importance of adequate sampling to ensure a correct diagnosis.