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Fibrocystic change is the most common disorder of the breast. It is most frequent during the reproductive years from 20-40 years peaking around menopause. It may be present in up to 60% of women and may be asymptomatic. The most common patterns are adenosis, cyst formation and fibrosis. Depending upon the degree of changes, the breast may have a lumpy bumpy appearance and feel. Calcifications may form and are identified on mammography. Occasionally the calcification pattern may be atypical, prompting a biopsy.

The disorder may be related to hormonal imbalance with an excess of estrogens. Oral contraceptive use may decrease the changes since it usually provides a balance of progesterone and estrogen. If there are no proliferative changes, there is no increased risk for developing breast carcinoma. The table below lists some important precursor conditions for the development of breast cancer.


Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Electron Microscopy
Differential Diagnosis  
Commonly Used Terms  
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Radial scars of the breast and breast carcinomas have similar alterations in expression of factors involved in vascular stroma formation

Timothy W. Jacobs, MD
Stuart J. Schnitt, MD
Xiaolian Tan, PhD
Lawrence F. Brown, MD

Hum Pathol 2002;33:29-38. Abstract quote

We recently reported that radial scars are an independent histologic risk factor for breast cancer. The reason for this association is not known. Given the importance of stromal–epithelial interactions in the pathogenesis of breast cancer, we studied radial scars for the expression of a number of factors known to be involved in the formation of vascular stroma in breast cancer.

In situ hybridization was performed on formalin-fixed paraffin sections using 35S-labeled riboprobes for collagen type 1, total fibronectin, extra domain A (ED-A)+ fibronectin, thrombospondin 1, vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF), and one of its endothelial receptors, kinase insert domain–containing receptor (KDR) (vascular endothelial growth factor receptor [VEGFR-2]). Expression levels in radial scars (9 cases) were compared with those in normal breast tissue (15 cases) and infiltrating ductal breast carcinoma (4 cases). Factor VIII–related antigen immunostaining was used to define the distribution of microvessels in radial scars, carcinoma, and normal breast tissue. Compared with normal breast tissue, the radial scars showed focally increased numbers of blood vessels and focally increased expression of messenger RNA (mRNA) for collagen type 1, total fibronectin, ED-A+ fibronectin, thrombospondin 1, VPF/VEGF, and KDR. This pattern of mRNA overexpression was similar to that seen in the 4 invasive cancers.

We conclude that there are similarities between radial scars and invasive breast cancers with regard to the level of mRNA expression for several factors involved in the formation of vascular stroma. These results suggest that a similar disturbance in stromal–epithelial interactions is present in both lesions.

Molecular and genetic abnormalities in radial scar.

Iqbal M, Shoker BS, Foster CS, Jarvis C, Sibson DR, Davies MP.

Clatterbridge Cancer Research Trust, J.K. Douglas Laboratories, Clatterbridge Hospital, Bebington, United Kingdom.

Hum Pathol 2002 Jul;33(7):715-22 Abstract quote

Hyperplasia of usual type (HUT) may be an early precursor of breast carcinoma and has been shown to contain molecular and genetic abnormalities previously seen in more advanced breast lesions, such as allelic imbalance (AI) and coexpression of estrogen receptor-alpha (ER) and the proliferation marker Ki67.

We have examined hyperplastic and other areas from within radial scar (RS) for such abnormalities, to explore whether such regions of RS are similar at the molecular and genetic level to histologically similar lesions found independent of RS. Abnormal expression of ER and Ki67 in hyperplastic foci and other histologically distinct areas within RS was detected by dual-label immunofluorescence. Subtle differences in expression patterns were seen compared to similar lesions outside RS, with a lower overall level of ER overexpression in HUT within RS (P = 0.0012) and less evidence of the abnormal ER association with Ki67 (P = 0.004). AI of chromosome 16q and 8p was detected in RS, indicating that at least some areas of RS are clonal and neoplastic, but no clear relationship to ER dysregulation was found. Different genetic losses seen in microdissected areas of the same RS indicated clonal differences between these areas.

The role of RS as a marker of malignancy and relative risk of breast cancer remains uncertain. Nonetheless, here we provide evidence that some molecular and genetic changes that occur to a greater degree in breast cancer and some premalignant breast lesions are present in a minority of RS.



Sampling of grossly benign breast reexcisions: a multidisciplinary approach to assessing adequacy.

Abraham SC, Fox K, Fraker D, Solin L, Reynolds C.

Department of Pathology, University of Pennsylvania Medical Center, Philadelphia 55905, USA.

Am J Surg Pathol 1999 Mar;23(3):316-22 Abstract quote

The widespread use of breast-conserving therapy in the treatment of early-stage breast cancer has resulted in increasing numbers of reexcision specimens requiring histologic assessment for residual disease and margin status. Because many reexcisions are performed for only microscopically positive or close margins, reexcision specimens often appear grossly negative and directed tissue sampling cannot be performed. The issue of adequate sampling in these specimens has not been addressed in the literature. A multidisciplinary approach to identifying the clinically important lesions in breast reexcisions and a cost-effective approach to tissue sampling are needed.

We reviewed 97 consecutive cases of grossly negative breast reexcisions in which all tissue had been embedded.

Forty-seven specimens contained residual invasive or in situ carcinoma and 50 were histologically negative. Detailed histologic findings were presented to a medical oncologist, a radiation oncologist, and a surgeon, who assessed the clinical impact of each diagnosis. Of the 47 positive specimens, 30 resulted in a major change in patient management (recommendation for additional surgery), 10 resulted in minor changes (alteration in radiation dose or adjuvant chemotherapy regimen), and 7 did not alter management. A total of 1867 blocks were submitted. If one block per centimeter of maximal tissue dimension had been submitted and the remainder of the specimen examined only if initial sections revealed invasive or in situ carcinoma, then 901 blocks would have been processed (52% reduction), but we would have missed an average of 3.7 cases resulting in a major change in therapy, and 3.3 cases resulting in a minor change. In contrast, two blocks per centimeter would have missed an average of less than one case each of diagnoses resulting in major and minor therapy changes (0.9 and 0.8 cases, respectively), and 315 (17%) fewer tissue blocks would have been processed.

We recommend submitting two blocks per centimeter in grossly benign reexcisions, and examining the remainder of the tissue only if carcinoma is detected on initial sections.


Adenosis tumour of the breast--a clinicopathological investigation of 27 cases.

Nielsen BB.

University Institute of Pathology, Kommunehospitalet, Aarhus, Denmark.

Histopathology 1987 Dec;11(12):1259-75 Abstract quote

Twenty-seven cases of palpable and/or tumour-forming adenosis in the female breast, called adenosis tumour, have been investigated. It is a rare lesion, which most often presents as a breast mass that clinically and histologically is sometimes misinterpreted as carcinoma.

The majority of patients were under the age of 45 years. Grossly, most tumours were firm or elastic and showed a grey or greyish-white cut surface. Furthermore, seven (26%) were granular and nine (34%) were microcystic, whereas none showed chalky streaks.

Microscopically, 20 cases were poorly circumscribed and seven cases were well circumscribed. In contradistinction to the often uniform growth pattern of tubular carcinoma, the adenosis tumours characteristically showed adenosis arranged in a mixture of eight different growth patterns.

The most frequent and also most extensive growth pattern was classical sclerosing adenosis and the least frequent was tubular adenosis. Another conspicuous feature in adenosis tumours was patchy growth in contrast to the stellate configuration of tubular carcinoma which is the most likely differential diagnosis. Other findings separating adenosis tumours from carcinomas were microcysts (93%), apocrine metaplasia (63%), luminal histiocytes (52%) and pseudopapillomas, called glomeruloid structures (48%). Epithelial changes that could cause anxiety about malignancy were frequently found and comprised epithelial hyperplasia (44%), epithelial atypia (26%) and fat or nerve infiltration (30%). Three patients were subjected to unnecessary mastectomy because of incorrectly diagnosed adenosis tumours.

Adenosis tumours and non-infiltrating carcinoma were found together in five cases, but their association is probably over represented due to selection. None of 18 pure adenosis tumours solely treated by excision had recurred at follow-up 1-9 years later (mean 3.75 years).

Assessment of 142 Stellate Lesions With Imaging Features Suggestive of Radial Scar Discovered During Population-based Screening for Breast Cancer.

Farshid G, Rush G.

From *BreastScreen SA and Division of Tissue Pathology, Institute of Medical and Veterinary Science, Adelaide, South Australia; and daggerBreastScreen SA, Wayville, South Australia.
Am J Surg Pathol. 2004 Dec;28(12):1626-1631. Abstract quote  

Because some lesions diagnosed as radial scars (RS) on core biopsy have been found to be malignant on excision, core biopsy has not had an established role in the assessment of RS. In our breast cancer-screening program, we have avoided core biopsy if RS is suspected on imaging. Recently, two reports have expanded the experience with core biopsy of RS, prompting this review of our assessment protocols for lesions suspected as being RS.

Between January 1996 and January 2003, stellate lesions with imaging features of RS in which core biopsy was omitted because of a presumptive radiologic diagnosis of RS are included. Demographic, radiologic, and cytologic data were correlated with the histologic findings in the excised specimen. On imaging, 9% (142) of all stellate lesions were suspected to be RS. Only 66.2% (94) were confirmed as RS on histology; 38 cases (28.6%) were carcinomas (36 invasive, 2 in situ) and 7% showed benign fibrocystic changes; 87.1% of the carcinomas required further surgery for positive margins. Axillary staging was also needed for the invasive cancers.

Among the histologically proven RS, 28 of 94 (29.8%) showed areas of atypical ductal hyperplasia, lobular neoplasia, ductal carcinoma in situ, or invasive carcinoma. These proliferations were typically focal and unpredictable and were usually completely excised by the initial diagnostic biopsy.

Core biopsy would be valuable in the assessment of lesions with imaging features suggestive of RS since 28.6% of such lesions are indeed carcinomas that mimic RS. Identification of these cancers would permit one stage breast and axillary surgery to be planned.

The policy of mammographic surveillance for lesions with nonmalignant core biopsies remains controversial because of the paucity of data. Ongoing evaluation is needed as more experience is reported.

Carcinoma and atypical hyperplasia in radial scars and complex sclerosing lesions: importance of lesion size and patient age.

Sloane JP, Mayers MM.

Department of Histopathology, Royal Marsden Hospital, Sutton, Surrey, UK

Histopathology 1993 Sep;23(3):225-31 Abstract quote

One hundred and twenty-six radial scars and complex sclerosing lesions from 91 women were examined to determine the incidence of and the clinical and pathological factors associated with the development of carcinoma and atypical hyperplasia within them.

There was a clear relationship between the presence of carcinoma and atypical hyperplasia and the size of the lesion. This was not, however, a progressive relationship, there being a cut-off point about 6-7 mm, below which carcinoma was very uncommon and above which it was relatively frequent. A similar relationship was seen with patient age. Carcinoma was not seen in lesions removed from women under 40, was rare in the decade 41-50 and was relatively common above this age but with no further increase in the over 60s.

A significantly higher incidence of carcinoma and atypical hyperplasia was encountered in scars detected by mammographic screening and could be explained by lesion size and the ages of the patients from which they were removed. No relationship was found between the presence of carcinoma within radial scars and complex sclerosing lesions and the existence of carcinoma in the residual breast tissue when direct extension was excluded.

The carcinomas identified in the scars were of variable type and included small and large cell ductal carcinoma in situ, lobular carcinoma in situ and invasive carcinoma of tubular and ductal types. In situ carcinoma and atypical hyperplasia involved a very variable percentage of the epithelium of the lesions with mean values for ductal carcinoma in situ of 32%, lobular carcinoma in situ 25% and atypical hyperplasia 25%.

Metaplastic carcinoma of the breast arising within complex sclerosing lesion: a report of five cases.

Denley H, Pinder SE, Tan PH, Sim CS, Brown R, Barker T, Gearty J, Elston CW, Ellis IO.

Department of Histopathology, Nottingham City Hospital, Nottingham, UK.

Histopathology 2000 Mar;36(3):203-9 Abstract quote

AIMS: This study presents a series of five cases in which metaplastic carcinoma, predominantly low-grade adenosquamous carcinoma, of the breast is seen arising within a background of a complex sclerosing lesion. This association has been recognized previously but has not been documented in detail. This study describes the characteristics of the components present in each case and discusses the existing literature. This observation adds further evidence to support an association between some types of invasive breast carcinoma and sclerosing lesions of the breast.

METHODS AND RESULTS: Four of these cases were received as referral cases for opinion. The fifth was received as part of the routine surgical workload within our own institution. Two patients presented following mammographic screening and three symptomatically; their mean age was 62 years (range 49-68). The mean lesion size was 16 mm (range 7-24). All five lesions showed features of a complex sclerosing lesion/radial scar in the form of central sclerosis with elastosis and radiating benign entrapped tubules. One had associated benign papillary structures and two had focal benign squamous metaplasia. Four cases showed coexisting but distinct areas of low-grade adenosquamous carcinoma with glandular and squamous epithelial differentiation in a spindle cell background. One case had associated undifferentiated spindle cell carcinoma. Detailed immunophenotypic characteristics of two cases are presented.

CONCLUSIONS: This series illustrates a postulated but previously unconfirmed association between an unusual form of metaplastic breast carcinoma (adenosquamous carcinoma) and complex sclerosing lesions. The mechanisms of induction of breast carcinoma are poorly understood but these observations further emphasize the potential for sclerosing lesion of the breast to be associated with, and possibly give rise to, invasive carcinoma of different types. The precise nature of the interaction between the pathological processes remains unclear.


Microglandular adenosis. A benign lesion simulating invasive mammary carcinoma.

Rosen PP.

Am J Surg Pathol 1983 Mar;7(2):137-44 Abstract quote

Microglandular adenosis (MGA) is a benign mammary disease in which small uniform acinar structures seem to grow haphazardly in the mammary parenchyma. While most often an inconspicuous microscopic lesion, MGA can cause a palpable tumor.

This report is based on a review of 13 patients who presented with palpable tumors which were composed in part or entirely of MGA. The mean age was 53 years. In two cases, the mass was painful; a third patient described changes in the size of the tumor with menstrual cycles. Four patients had carcinoma associated with MGA. Two women had MGA coexistent with in situ lobular and intraductal carcinoma, respectively, when the carcinoma was diagnosed. Two other patients developed invasive carcinoma at intervals of 6 and 18 years subsequent to a biopsy of MGA. Both patients had hyperplastic foci in the MGA prior to developing carcinoma.

These findings suggest that complete excision of MGA is appropriate and that it is prudent for patients with MGA to seek regular clinical follow-up.

Carcinoma of the breast arising in microglandular adenosis.

James BA, Cranor ML, Rosen PP.

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York.

Am J Clin Pathol 1993 Nov;100(5):507-13 Abstract quote

Breast carcinoma arose in or in conjunction with microglandular adenosis (MGA) in 14 of 60 (23%) patients with MGA listed in the authors' files.

This article describes the clinicopathologic and immunohistochemical features and prognosis of these carcinomas. The median patient age was 47 years (range, 26-68 years). All patients had a mass. Six (43%) had a family history of breast carcinoma. Lymph node metastases were found in 3 of 11 axillary dissections. Ten patients treated by mastectomy were recurrence-free, with a median follow-up of 57 months (range, 3-108 months). Two of three patients treated by excisional surgery were recurrence-free 12 and 105 months later. The third woman had bone metastases at 51 months and was alive 98 months after treatment. Carcinoma arose in the MGA in 13 patients.

In these patients, in situ carcinoma was found in expanded MGA glands composed of cells with vesicular poorly differentiated nuclei. One patient with benign MGA had carcinoma develop in the opposite breast that was not associated with MGA. When it arose in MGA, basement membranes were present in benign MGA and in situ carcinoma but tended to be disrupted in invasive foci that appeared to be formed by coalescent MGA glands. Strong immunoreactivity for cytokeratin, S-100, and cathepsin D was detected in carcinomas. Two carcinomas had nuclear progesterone receptors, and one of these had estrogen receptors. One carcinoma had positive findings for HER-2neu, and four had immunoreactivity for p53 protein.

The following conclusions were drawn from these observations: (1) carcinomas arising in MGA have a distinctive histopathologic pattern; (2) the carcinomas are composed of epithelial cells (cytokeratin positive, actin negative) that are strongly immunoreactive for S-100 protein and cathepsin D; and (3) with a median follow-up of nearly 5 years, patients with these carcinomas had a relatively favorable prognosis, despite histopathologic and immunohistochemical features usually associated with a poor prognosis.

Carcinoma Arising in Microglandular Adenosis: An Immunohistochemical Analysis of 20 Intraepithelial and Invasive Neoplasms.

Koenig C, Dadmanesh F, Bratthauer GL, Tavassoli FA.

Department of Gynecologic and Breast Pathology, The Armed Forces Institute of Pathology, Washington, DC.

Int J Surg Pathol 2000 Oct;8(4):303-315 Abstract quote

Microglandular adenosis (MGA) of the breast is an uncommon, benign lesion that may mimic invasive carcinoma and has recently been recognized as having significant premalignant potential. When carcinomas arise in MGA, there is often a transition from ordinary MGA to atypical MGA (AMGA) to carcinoma.

Nineteen cases of carcinoma arising in MGA are reported: 7 invasive carcinomas, 7 intraductal carcinomas (DCIS), and 5 with both invasive and intraductal carcinoma. A single case of AMGA without carcinoma is also reported.

The 20 patients ranged in age from 36 to 81 years (mean 52). The most common clinical presentation was either a palpable mass (13 patients) or a mammographic abnormality (4 patients). All 20 cases contained AMGA, and in some cases AMGA was the predominant lesion. In 18 of the 19 cases with carcinoma, there was a clear transition from AMGA to the carcinoma. Twelve cases contained ordinary MGA, but in only 2 cases was MGA a prominent component of the lesion.

In contrast to ordinary MGA, the glands of AMGA were more irregularly shaped, closely packed, and cytologically atypical and tended to lack secretions. A solid, occlusive proliferation of cells in the tubules was seen in 10 cases. All 12 examples of in situ carcinoma were either grade 2 or 3 and typically showed a solid proliferation of severely atypical cells within the glands; a cribrifrom pattern was also present in 1 case. The invasive carcinomas were morphologically diverse and included 2 with a basaloid morphology and 2 metaplastic carcinomas.

Various immunostains were performed, and each lesion (AMGA, in situ, and invasive carcinoma) was separately assessed for immunoreactivity. As expected, S-100 was positive in the vast majority of AMGA and in situ carcinomas and in all 12 invasive carcinomas. S-100beta was also positive in the majority of cases although the staining was weaker. Laminin and type IV collagen highlighted the basement membrane around the AMGA and in situ carcinoma and are useful stains in difficult cases. Except for a single case, ER and PR were negative in all lesions. Cytokeratin 7 (CK 7) was positive, while cytokeratin 20 (CK 20) was negative in all cases. Immunostains for CK903 showed no reactivity in any of the invasive carcinomas, in situ carcinomas, or atypical MGA but was focally present in the associated MGA in 2 of the 8 cases studied. Immunostains for MIB-1 and p53 were semiquantitatively assessed and both were positive in AMGA but tended to show a more intense staining in the carcinomas. Five cases were also studied for immunoexpression of alpha-1 antitrypsin (AAT), alpha-1 antichymotrypsin (ACTP), lysozyme, and salivary gland amylase.

All 5 invasive carcinomas were positive for ACTP, though the staining was very focal in about 10% of the cells in a basaloid carcinoma. The in situ carcinoma as well as the AMGA in 4 of the 5 cases were positive for ACTP. Three of the 5 invasive carcinomas were positive for AAT in 10% to 40% of the cells. The most intense positivity for AAT and ACTP was in cells with coarsely granular apocrine appearance evident in 2 of the 5 cases. Four of the 5 invasive carcinomas were positive for lysozyme in 10% to 50% of the cancer cells; the in situ carcinoma and the associated AMGA showed similar immunoreaction in each case. None of the 5 cases showed convincing positivity for salivary gland amylase. The MGA in all 5 cases was negative for AAT and ACTP; the MGA in 1 of the 5 cases was positive for lysozyme.

This study confirms the potential of MGA to develop into an invasive carcinoma, more clearly defines the features of AMGA, highlights the importance of AMGA in the evolution of carcinoma from MGA, and expands our knowledge of the immunophenotype of AMGA and the carcinomas arising from it. The diagnostic criteria briefly noted previously for diagnosis of AMGA and carcinoma arising in MGA are expanded and formally proposed.


Tubular adenosis of the breast. A distinctive benign lesion mimicking invasive carcinoma.

Lee KC, Chan JK, Gwi E.

Department of Pathology, Queen Elizabeth Hospital, Kowloon, Hong Kong.

Am J Surg Pathol 1996 Jan;20(1):46-54 Abstract quote

Tubular adenosis, a term first coined by Oberman, is an uncommon benign lesion of the breast that may mimic invasive carcinoma. There is no formal description of this condition in the literature.

We report the findings on six specimens from five patients (one with bilateral disease), including three that showed cancerization by intraductal carcinoma (DCIS). The ages of the patients ranged from 40 to 82 years. One patient presented with a 3-cm breast mass, and the others were found in specimens resected for infiltrating ductal carcinoma (two specimens) or DCIS (three specimens).

The histologic hallmark of tubular adenosis was haphazard proliferation of elongated tubules that were noncrowded, narrow, and sometimes branching. There was no lobular arrangement or, at most, vague lobular grouping, with some tubules often extending into the fat. The tubules contained basophilic or granular eosinophilic secretion. The stroma was sclerotic to edematous. The tubules were lined by bland-looking ductal cells and were surrounded by an intact myoepithelial layer, a phenomenon well highlighted by immunostaining for muscle-specific actin (HHF-35) or S-100 protein.

In three specimens, the tubular adenosis was cancerized by noncomedo DCIS, producing a pattern strongly mimicking infiltrating carcinoma; the in situ nature of the carcinoma was confirmed by actin immunoreactivity in the residual myoepithelium as well as by the presence of architecturally similar tubular adenosis in the vicinity. Tubular adenosis shows an infiltrative growth similar to microglandular adenosis and adenomyoepithelial adenosis, but it differs from them by the interdigitating tubular configuration and also differs from microglandular adenosis by the presence of myoepithelium. Tubular adenosis can be distinguished from sclerosing adenosis by the lack of obvious lobular architecture or whorled arrangement and wider separation of the tubules.

Tubular adenosis appears to be a benign lesion per se, but whether it has premalignant potential remains to be determined. The importance of recognizing this entity lies in its being potentially mistaken for invasive carcinoma, especially at intraoperative frozen section or when the lesion is cancerized by DCIS.



Microglandular adenosis, apocrine adenosis, and tubular carcinoma of the breast. An immunohistochemical comparison.

Eusebi V, Foschini MP, Betts CM, Gherardi G, Millis RR, Bussolati G, Azzopardi JG.

Department of Anatomic Pathology, University of Bologna, Italy.

Am J Surg Pathol 1993 Feb;17(2):99-109 Abstract quote

Four cases of microglandular adenosis (MA), together with four cases of apocrine adenosis (AA) and 10 cases of tubular carcinoma (TC) of the breast were studied at the light and immunohistochemical level.

One case of MA was studied with electron microscopy. MA is characterized by an absence of myoepithelial cells (ME), epithelial membrane antigen (EMA), and gross cystic disease fluid protein (GCDFP-15). The absence of EMA in MA makes it unique among benign glandular hyperplasias of the breast. AA contains myoepithelial cells and a distinct basal lamina. It is characterized by the presence of GCDFP-15, the specific apocrine marker, which is not present in MA. TC lacks both myoepithelial cells and a basal lamina. It is negative for GCDFP-15. Periductal and vascular elastosis are common and usually prominent, whereas they are not found in either MA and AA. Other stromal changes further distinguish the three lesions.

These three distinct entities can be separated objectively and unequivocally and it is essential that this be done so as to prevent confusion.


Microglandular adenosis of the breast. An immunohistochemical comparison with tubular carcinoma.

Diaz NM, McDivitt RW, Wick MR.

Lauren V. Ackerman Laboratory of Surgical Pathology, Department of Pathology, Barnes Hospital.

Arch Pathol Lab Med 1991 Jun;115(6):578-82 Abstract quote

Microglandular adenosis (MA) of the breast is a benign, disorganized proliferation of glands lined by a single layer of cells. As such, differential diagnosis between MA and tubular carcinoma may be challenging in selected cases.

A panel of antibodies was applied to 10 cases of MA and 10 of tubular carcinoma to investigate the potential benefit of immunohistochemistry in the separation of these lesions and the possible role of myoepithelial cells in MA. The luminal cells in nine cases of MA were surrounded by a cuff of muscle-specific actin-reactive cells, which also coexpressed cytokeratin and vimentin. The immunophenotype of these cells is characteristic of myoepithelial differentiation, which was heretofore thought to be lacking in MA.

This finding demonstrates that myoepithelial cells are indeed present in MA subjacent to luminal epithelial cells; moreover, it distinghuishes MA from tubular carcinoma, all examples of which were actin negative in this analysis. In addition, circumferential type IV collagen deposition was observed around constituent glands of MA in nine cases but was lacking in all tubular carcinomas. Other markers included in this evaluation (S100 protein, gross cystic disease fluid protein 15, carcinoembryonic antigen, estrogen receptor protein) were of no differential diagnostic value.


Microglandular adenosis of the breast. A clinicopathologic study of 11 cases with ultrastructural observations.

Tavassoli FA, Norris HJ.

Am J Surg Pathol 1983 Dec;7(8):731-7 Abstract quote

The clinical and pathologic features of 11 examples of microglandular adenosis of the breast are presented.

Microglandular adenosis is a rare, benign lesion that is easily confused with carcinoma. It is characterized by a concentrated proliferation of round glands with open lumens in a densely homogeneous stroma that clearly delineates microglandular adenosis from the adjacent uninvolved breast. The glands are lined by a single layer of cells with distinctly vacuolated or granular cytoplasm.

Ultrastructurally, the single layer of epithelial cells lacks cytoplasmic protrusions and is surrounded by a thick multilayered basement membrane. Light- and electron-microscopic features that help distinguish microglandular adenosis from well-differentiated (tubular) carcinoma and sclerosing adenosis, entities with which it is easily confused, are discussed.


Cytology of papillary proliferations

Ann Diagn Pathol 2001;5:34-42

Retrospective Review:
Papanicolaou and giemsa stained smears from 33 aspirates and their corresponding histology were reviewed. Of these, 28 had an initial cytologic diagnosis or suspicion of papillary neoplasm, while five cases were not diagnosed cytologically as papillary but the histologic diagnosis was a papillary neoplasm. Cytologic features evaluated included cellularity, architecture, apocrine/single/columnar cells, nuclear atypia, intranuclear inclusions, calcifications, background, myoepithelial cells, and bipolar, naked nuclei.

Discriminating cytologic features grouped by final histologic diagnosis were as follows: Papillary neoplasm (14 cases): Hemorrhagic/cystic background, 3-dimensional papillary clusters, columnar cells, and fibrovascular cores. Myoepithelial cells within clusters and background naked, bipolar nuclei were inconspicuous. Fibroadenoma (4 cases): Two-dimensional branching clusters often with folding, moderate myoepithelial cells in clusters, moderate to numerous background bipolar nuclei, often forming doublets in smear background, cellular stroma. Ductal carcinoma (11 cases): Papillary ductal carcinoma in situ in 5 of 11 cases, cribriform/tubular architecture in 6 of 11. Absence or paucity of myoepithelial within clusters and background bipolar nuclei was noted. Fibrocystic change (4 cases): Two-dimensional clusters, moderate myoepithelial cells within clusters, and moderate bipolar nuclei in the background.

The presence and quantity of myoepithelial cells, bipolar naked nuclei in the background, and ductal cell architecture were the only consistently useful cytologic features in distinguishing breast lesions with a papillary pattern.


Gynecomastia-like Changes of the Female Breast A Clinicopathologic Study of 4 Cases

Yong Kang, etal.

Arch Pathol Lab Med 2001;125:506–509. Abstract quote

Objectives.—Gynecomastia-like changes of the female breast are only sparsely reported and are not well defined in the literature to our knowledge. Our objectives were to determine the incidence, clinical presentation, mammographic findings, and the medical background of patients with these changes.

Design.—Two thousand seven hundred nine female breast surgical cases from 1995 to 1999 were searched by SNOMED. Three observers further reviewed all cases with gynecomastia-like changes. Strict criteria were developed and cases that fulfilled the criteria were analyzed further.

Results.—We found the incidence of female gynecomastia-like changes to be 0.15% (4/2709) of all female breast lesions, which represents an underestimation. Patients were usually young and had an average age of 32 years. The usual clinical presentation was a palpable mass with a size ranging from about 3.5 × 2 × 2 cm to 5 × 4 × 2.5 cm. Mammography showed either negative findings or a nonspecific density. Gross examination of these specimens revealed no distinct lesions. Histologically, the lesions consisted of ductal hyperplasia with periductal stromal fibrosis or edema. They were associated with fibrocystic changes in the adjacent breast. The patients had no significant medical history.

Conclusion.—We propose that the gynecomastia-like change is a specific benign entity within the spectrum of benign fibrocystic changes and that it usually occurs in young patients.

  Arch Pathol Lab Med. 2000;124:844–847

Rosen, PP. Rosen's Breast Pathology. Philadelphia, Pa: Lippincott-Raven. 1997:611–613.

Ductal hyperplasia and periductal stromal fibrosis or edema and slight lymphocytic infiltrate.

No terminal duct–lobular units present in area of involvement.

The involved area should be greater than 1 scanning field (2 × 10) in an excision specimen.

In case of a core biopsy, 1 fragment should be involved entirely and the fragment should be at least 1 cm in length.

No associated mammary hamartomatous changes, areas of juvenile hyperplasia, or juvenile fibroadenoma.


Lobular carcinoma in situ in sclerosing adenosis. A potential source of confusion with invasive carcinoma.

Fechner RE

Am J Surg Pathol 1981 Apr;5(3):233-9 Abstract quote

A group of five different patients who had extensive sclerosing adenosis with ductules containing cells characteristic of lobular carcinoma were studied (six breasts in all). Because of the complex arrangement of ductules in sclerosing adenosis, the possibility of an invasive lobular carcinoma was considered in two cases.

The distinction between sclerosing adenosis with lobular carcinoma in situ and infiltrating lobular carcinoma rests with the overall architecture of the lesion as seen at low power. Foci of sclerosing adenosis, with or without carcinoma in situ, have dilated ductules peripherally, and narrow ones centrally, whereas infiltrating lobular carcinoma has no overall organization. Because of the diagnosis of lobular carcinoma in situ, extended simple mastectomy was performed in three patients, and as expected, the lymph nodes were free of tumor.


Histologic Changes Relative Risk for Breast Carcinoma
Mild ductal hyperplasia, adenosis, cystic changes, apocrine metaplasia
No increased risk
Sclerosing adenosis, moderate to florid epithelial hyperplasia, papillomas
Atypical ductal and atypical lobular hyperplasia

Nonmalignant lesions in breast core needle biopsies: to excise or not to excise?

Jacobs TW, Connolly JL, Schnitt SJ.

Am J Surg Pathol 2002 Sep;26(9):1095-110 Abstract quote

Large core needle biopsies using stereotactic mammography or ultrasound guidance are now commonly performed as the initial diagnostic approach to nonpalpable breast lesions. Although the subsequent management of patients with invasive cancer, ductal carcinoma in situ, and most benign lesions diagnosed on core needle biopsy specimens is straightforward, certain nonmalignant lesions pose dilemmas with regard to the most appropriate clinical management following core needle biopsy.

The purpose of this article is to review the available data regarding several nonmalignant breast lesions, which when encountered in core needle biopsy specimens raise repeated management questions. These include atypical ductal hyperplasia, lobular neoplasia (atypical lobular hyperplasia and lobular carcinoma in situ), papillary lesions, radial scars, fibroepithelial lesions, mucocele-like lesions, and columnar cell lesions.

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Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

Commonly Used Terms

Adenosis-Increase in glandular acinar units per lobule. If the gland lumens are enlarged, it is termed blunt duct adenosis. If the lumens are distorted, it is called sclerosing adenosis.

Apocrine metaplasia-A benign metaplastic change where the normal ductal epithelium is replaced by large eosinophilic cells with abudant cytoplasm.

Fibrosis-Scarring fibrosis frequently secondary to ruptured cysts and extravasation of fluid.

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Learn the basic disease classifications of cancers, infections, and inflammation

Commonly Used Terms
This is a glossary of terms often found in a pathology report.

Diagnostic Process
Learn how a pathologist makes a diagnosis using a microscope

Surgical Pathology Report
Examine an actual biopsy report to understand what each section means

Special Stains
Understand the tools the pathologist utilizes to aid in the diagnosis

How Accurate is My Report?
Pathologists actively oversee every area of the laboratory to ensure your report is accurate

Got Path?
Recent teaching cases and lectures presented in conferences

Internet Links

Last Updated December 9, 2004

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