Apocrine Ductal Carcinoma Research Articles

Apocrine carcinoma of the breast: Review

Abstract Apocrine carcinoma of the breast is a rare subtype of breast carcinoma, which only presents as 4% among patients with breast cancer. The percentage varies based on the diagnostic criteria used by each institution to classify apocrine carcinoma. Several confusing terms used in previous studies, including apocrine ductal carcinoma in situ (ADCIS), apocrine morphology in lobular carcinoma in situ (Apocrine LCIS), apocrine-like invasive carcinoma, pure apocrine carcinoma, molecular apocrine tumors (MATs), and triple-negative apocrine carcinoma of the breast (TNAC). The treatment, prognosis, and molecular profiles are also diverse. Pure apocrine carcinoma has stricter criteria for diagnosis, requiring more than 90% of cells showing apocrine morphology and classic IHC characteristics of ER-negative, PR-negative, and AR-positive in at least 10% of tumor cell nuclei. Research related to prognosis is diverse due to the difficulty of unifying the diagnostic criteria. Current evidence of treatment is geared toward the use of neoadjuvant chemotherapy and anti-androgen therapy when AR is present, accompanied by other treatments if biomarkers are present, such as HER2, PI3K, or CDK4/6. This article focuses on clearly summarizing different subtypes and management of apocrine carcinoma of the breast.

Clinicopathological analysis of benign mammary ductal cystic papillomatosis with loss of myoepithelial cells

Objective: To investigate the histopathological and immunohistochemical characteristics of benign apocrine cystic papillary hyperplasia of the breast with loss of myoepithelial cell layer. Methods: The clinical data, histopathological features and immunohistochemical profile of patients with benign apocrine cystic papillary hyperplasia of breast with loss of myoepithelial cell layer from January 2016 to December 2021 were examined, in which six patients were identified. Results: All six patients were female, aged 36-61 years (median 46 years), who presented with a breast mass; three cases were from the left breast and three cases were from the right breast. Microscopic examination of all cases showed breast hyperplasia with apocrine cysts, accompanied by different degrees of micropapillary and papillary hyperplasia of apocrine cells. One case was associated with lobular carcinoma in situ, and one case was associated with apocrine ductal carcinoma in situ with intraductal dissemination in adenosis. Immunohistochemical staining of CK5/6, p63, SMA, SMMHC, Calponin and CD10 showed complete absence of myoepithelial cell layer surrounding ducts in apocrine cystic papillary hyperplasia. Conclusions: The myoepithelial cells of apocrine cystic papillary hyperplasia of the breast may undergo abnormal changes and may even be completely lost. The diagnosis should be comprehensively considered along with cytomorphological and histological features to avoid overdiagnosis.

The diagnostic utility of EZH2 H-score and Ki-67 index in non-invasive breast apocrine lesions

In diagnostic breast pathology, there is no reliable applicable immunostain to help discern atypical and in situ apocrine lesions from benign apocrine tissue. At present, the diagnosis of non-invasive apocrine lesions remains challenging with current diagnoses rendered based on discrete morphologic characteristics on conventional hematoxylin and eosin staining. Interobserver variability is significant even among subspecialists partly due to lack of adjuvant diagnostic immunohistochemical stains. Herein, we set to elucidate the potential utility of EZH2 and Ki-67 immunostains as tangible tools in non-invasive apocrine proliferations. A cohort of apocrine breast lesions [Benign apocrine hyperplasia (BAH), n = 10; Atypical apocrine hyperplasia (AAH), n = 16; Apocrine ductal carcinoma in situ (ADCIS), n = 12] were subjected to EZH2 immunostaining and analyzed via H-scoring of nuclear expression. Mean H-scores for EZH2 progressively increased from BAH (23.5), to AAH (47.4) and ADCIS (196.4), and showed a significant difference utilizing the Kruskal-Wallis test (p < 0.0001). Further interrogation of Ki-67 demonstrated incremental expression from BAH to AAH and ADCIS at 1.6 %, 4.7 % and 24.7 %, respectively (p < 0.0001, Kruskal-Wallis test), suggesting an association with increased proliferation. Our results demonstrate that a combination of EZH2 and Ki-67 immunostaining may be employed in differentiating among challenging apocrine breast lesions and suggest a putative diagnostic utility for EZH2 and Ki-67 in non-invasive apocrine breast lesions.

Apocrine lesions of the breast: part 1 of a two-part review: benign, atypical and in situ apocrine proliferations of the breast

Apocrine morphology is a common phenomenon encountered in everyday breast pathology practice, and is defined as cuboidal or columnar cells exhibiting abundant eosinophilic granular cytoplasm, prominent apical granules, a low...

Atypical Apocrine Adenosis: Diagnostic Challenges and Pitfalls.

Apocrine change in the breast is an extremely common finding. In most cases, the benign or malignant nature of the lesion is easily recognized. Apocrine adenosis is used to describe sclerosing adenosis with apocrine change. The term apocrine atypia is used when there is significant cytologic atypia in apocrine cells, characterized by a 3-fold nuclear enlargement, prominent/multiple nucleoli, and hyperchromasia. Atypical apocrine adenosis is diagnosed when apocrine adenosis and apocrine atypia are superimposed. However, there are no definite criteria to distinguish atypical apocrine adenosis from apocrine ductal carcinoma in situ. Immunohistochemical markers can be confounding and may lead to erroneous diagnoses. Atypical apocrine features in sclerosing lesions may be misinterpreted as invasive carcinoma if the underlying lesion is not recognized. In the absence of definite features of malignancy, the diagnosis of apocrine ductal carcinoma in situ may be extremely difficult. In the present article, we review atypical apocrine adenosis focusing on diagnostic challenges and their implications on clinical management.

Epidemiological and histopathological analysis of 40 apocrine sweat gland carcinomas in dogs: a retrospective study

Abstract Introduction: Apocrine sweat gland carcinomas (ASGCs) are malignant neoplasms of dogs and other animals, rarely reported worldwide. The aim of this study was to summarise the occurrence of this cancer in a population of dogs in Poland between 2009 and 2014 with regards to histological features and body location of the tumours, as well as age, sex and breed of the cancer-affected dogs. Material and Methods: The study involved 40 canine ASGC cases diagnosed in five national veterinary pathology laboratories. The material was processed according to routine histological methods. Results: Histological types of the tumours involved simple and complex apocrine carcinoma of cystic/papillary (62.5%), solid (15%), and tubular type (12.5%), as well as apocrine ductal carcinoma (10%). The epidemiological analysis revealed peak incidence of the cancer in dogs between 8 and 14 years of age, with the most commonly affected sites being forelimbs and thorax. The highest number of the cancer cases was diagnosed in mixed breed dogs and German Shepherds; no sex predilection was noted. Conclusion: To the authors’ knowledge, this is the first report recounting the study on canine malignant apocrine sweat gland tumours in Poland providing detailed phenotypical and histological data, which are otherwise rarely described in veterinary literature. This type of cancer appears to be diagnosed more frequently in dogs than in humans. Being an easily accessible material for research, canine ASGCs might serve as a relevant animal model for studies related to pathogenesis of sweat gland tumours.

Apocrine Ductal CarcinomaIn Situof the Breast Presented Mass with Morphological Change on Follow-Up Ultrasound: A Report of Case

2012;67(6):461-464 461 서론 유방의 아포크린 화생(apocrine metaplasia)은 종말관 소엽 단위(terminal duct lobular unit)의 소엽에서 발생하는 양성상 피 변화이며 유방의 섬유낭병(fibrocystic disease)에서 흔히 발 견되는 조직학적 소견이다. 유방의 아포크린 변화는 양성질환 뿐만 아니라 상피내암종(carcinoma in situ)과 침윤성 유방암 (invasive carcinomas) 같은 악성질환에서도 관찰될 수 있다 (1). 비정형 아포크린 화생(apocrine metaplasia with atypia) 과 아포크린 상피내암종(apocrine ductal carcinoma in situ) 은 유방 아포크린 병변의 병리적 스펙트럼이며 병리적 감별이 어 려울 수 있다(2). 아포크린 화생은 대개 초음파상에서 내부의 격막을 포함하는 복합 낭성 병변(complex-echoic mass)으로 보이게 되고 아포크린 상피내암종의 경우에도 유사한 초음파소 견을 보이게 된다. American College of Radiology Breast Imaging Reporting and Data System (ACR BI-RADS)에 따르면 복합성 낭성 병변은 범주 4에 해당할 수 있으며, 또한 범주 3의 추적관찰상 크기나 모양의 변화를 보이게 되면 범주 4로 승급 하여 조직검사를 필요로 하게 된다(3). 복합 낭성 병변 중 미세 침생검(fine-needle aspiration)을 시행하지 않고 중심 침생검 (core-needle biopsy)을 하는 경우는 초음파상에서 명확한 고 형 성분을 포함하는 병변이거나, 유방촬영술에서 군집성 석회 화 또는 구조왜곡 같은 의심 병변을 보이거나 포함된 고형성분 이 적어서 미세침생검이 어려운 경우이다(4). 저자들은 유방의 양성의심 병변의 추적관찰 중 초음파상에서 형태 변화가 보여 초음파 유도하 생검검사를 시행하였고, 비정형 아포크린 화생 이 발견되어 유방절제술을 시행한 결과 아포크린 상피내암종으 로 확진된 증례에 대해 보고하고자 한다.

Intracytoplasmic Lipid Accumulation in Apocrine Carcinoma of the Breast Evaluated With Adipophilin Immunoreactivity

Although apocrine carcinoma is a distinct histologic entity, there is no immunohistochemical marker to confirm apocrine differentiation with high sensitivity and specificity, and its differential cytologic characteristics are still not fully clarified. Despite the foamy cytoplasm of some apocrine carcinomas and the existence of lipid in the normal apocrine gland, intracytoplasmic lipid in apocrine carcinomas has not been fully explored. By using immunohistochemistry for adipophilin, which is a specific marker of lipid accumulation that can be applied to paraffin sections, we examined intracytoplasmic lipid in apocrine carcinomas. Twenty-four of 26 (92%) apocrine carcinomas and 38 of 116 (33%) nonapocrine carcinomas contained intracytoplasmic lipid. The frequency of adipophilin-positive cases was significantly higher in apocrine carcinomas compared with nonapocrine carcinomas (P<0.01). The positive cell rate per tumor ranged from 10% to 70% (mean, 29%) for apocrine carcinomas. The staining density was heterogeneous from cell to cell. There was no difference in the staining pattern of adipophilin between apocrine ductal carcinoma in situ and invasive apocrine carcinoma or between eosinophilic cells and foamy cells. Sporadic or mosaic distribution of adipophilin-positive cells throughout the tumor and microvesicular or fine granular cytoplasmic staining with heterogeneous density were characteristic features of apocrine carcinoma. Although intracytoplasmic lipid was identified in most apocrine carcinomas, none of the apocrine carcinomas contained prominent intracytoplasmic lipid in >90% of the tumor cells; thus, the criteria for lipid-rich carcinoma was not fulfilled. However, the immunohistochemical study suggests that lipid-rich carcinomas are closely related to apocrine carcinomas.

Apocrine Ductal Carcinoma In Situ Involving a Sclerosing Lesion With Adenosis: Report of a Case

Apocrine metaplasia is a ubiquitous component of the mammary fibrocystic change spectrum. Although mostly associated with cysts, apocrine metaplasia can also present as a proliferative lesion, rarely with cytologic atypism. Apocrine atypia is characterized by 3-fold nuclear enlargement, multiple nucleoli, and hyperchromatism and generally arises in florid or radial sclerosing lesions. Dramatic apocrine atypia may be very difficult to distinguish from apocrine ductal carcinoma in situ. The latter is distinguished from apocrine atypia by greater extent of the lesion (>0.4 cm) and the presence of greater nuclear pleomorphism with nuclear membrane irregularity. The clinical significance of apocrine atypia is poorly understood and reflects the lack of published outcome studies. Herein, I report a case in which apocrine ductal carcinoma in situ presented as atypical apocrine adenosis in a needle core breast biopsy. It illustrates the problem of assessing apocrine atypia and apocrine ductal carcinoma in situ in small samples.

Apocrine Ductal Carcinoma In Situ Involving a Sclerosing Lesion With Adenosis: Report of a Case

Apocrine metaplasia is a ubiquitous component of the mammary fibrocystic change spectrum. Although mostly associated with cysts, apocrine metaplasia can also present as a proliferative lesion, rarely with cytologic atypism. Apocrine atypia is characterized by 3-fold nuclear enlargement, multiple nucleoli, and hyperchromatism and generally arises in florid adenosis or radial sclerosing lesions. Dramatic apocrine atypia may be very difficult to distinguish from apocrine ductal carcinoma in situ. The latter is distinguished from apocrine atypia by greater extent of the lesion (>0.4 cm) and the presence of greater nuclear pleomorphism with nuclear membrane irregularity. The clinical significance of apocrine atypia is poorly understood and reflects the lack of published outcome studies. Herein, I report a case in which apocrine ductal carcinoma in situ presented as "atypical apocrine adenosis" in a needle core breast biopsy. It illustrates the problem of assessing apocrine atypia and apocrine ductal carcinoma in situ in small samples.

Molecular characterization of apocrine carcinoma of the breast: Validation of an apocrine protein signature in a well-defined cohort

Invasive apocrine carcinomas (IACs), as defined by morphological features, correspond to 0.3–4% of all invasive ductal carcinomas (IDC), and despite the fact that they are histologically distinct from other breast lesions there are currently no standard molecular criteria available for their diagnosis and no unequivocal information as to their prognosis. In an effort to address these concerns we have been using protein expression profiling technologies in combination with mass spectrometry and immunohistochemistry (IHC) to discover specific biomarkers that could allow us to molecularly characterize these lesions as well as to dissect some of the steps in the processes underlying breast apocrine metaplasia and development of precancerous apocrine lesions. Establishing these apocrine-specific markers as best practice for the routine pathology evaluation of breast cancer, however, will require their validation in large cohorts of patients. Towards this goal we have composed a panel of antibodies against components of an apocrine protein signature that includes probes against the apocrine-specific markers 15-prostaglandin dehydrogenase (15-PGDH), and acyl-CoA synthetase medium-chain family member 1 (ACSM1), in addition to a set of categorizing markers that are consistently expressed (AR, CD24) or not expressed (ERα, PgR, Bcl-2, and GATA-3) by apocrine metaplasia in benign breast lesions and apocrine sweat glands. This panel was used to analyze a well-defined cohort consisting of 14 apocrine ductal carcinoma in situ (ADCIS), and 33 IACs diagnosed at the Cancer Institute Hospital, Tokyo between 1997 and 2001. Samples were originally classified on the basis of cellular morphology with all cases having more than 90% of the tumour cells exhibiting cytological features typical of apocrine cells. Using the expression of 15-PGDH and/or ACSM1 as the main criterion, but taking into account the expression of other markers, we were able to identify unambiguously 13 out of 14 ADCIS (92.9%) and 20 out of 33 (60.6%) IAC samples, respectively, as being of apocrine origin. Our results demonstrate that IACs correspond to a distinct, even if heterogeneous, molecular subgroup of breast carcinomas that can be readily identified in an unbiased way using a combination of markers that recapitulate the phenotype of apocrine sweat glands (15-PGDH +, ACSM1 +, AR +, CD24 +, ERα −, PgR −, Bcl-2 −, and GATA-3 −). These results pave the way for addressing issues such as prognosis of IACs, patient stratification for targeted therapeutics, as well as research strategies for identifying novel therapeutic targets for developing new cancer therapies.

15-Prostaglandin Dehydrogenase Expression Alone or in Combination with ACSM1 Defines a Subgroup of the Apocrine Molecular Subtype of Breast Carcinoma

Established histopathological criteria divide invasive breast carcinomas into defined groups. Ductal of no specific type and lobular are the two major subtypes accounting for around 75 and 15% of all cases, respectively. The remaining 10% include rarer types such as tubular, cribriform, mucinous, papillary, medullary, metaplastic, and apocrine breast carcinomas. Molecular profiling technologies, on the other hand, subdivide breast tumors into five subtypes, basal-like, luminal A, luminal B, normal breast tissue-like, and ERBB2-positive, that have different prognostic characteristics. An additional subclass termed "molecular apocrine" has recently been described, but these lesions did not exhibit all the histopathological features of classical invasive apocrine carcinomas (IACs). IACs make up 0.5-3% of the invasive ductal carcinomas, and despite the fact that they are morphologically distinct from other breast lesions, there are presently no standard molecular criteria available for their diagnosis and as a result no precise information as to their prognosis. Toward this goal our laboratories have embarked in a systematic proteomics endeavor aimed at identifying biomarkers that may characterize and subtype these lesions as well as targets that may lead to the development of novel targeted therapies and chemoprevention strategies. By comparing the protein expression profiles of apocrine macrocysts and non-malignant breast epithelial tissue we have previously reported the identification of a few proteins that are specifically expressed by benign apocrine lesions as well as by the few IACs that were available to us at the time. Here we reiterate our strategy to reveal apocrine cell markers and present novel data, based on the analysis of a considerably larger number of samples, establishing that IACs correspond to a distinct molecular subtype of breast carcinomas characterized by the expression of 15-prostaglandin dehydrogenase alone or in combination with a novel form of acyl-CoA synthetase medium-chain family member 1 (ACSM1). Moreover we show that 15-prostaglandin dehydrogenase is not expressed by other breast cancer types as determined by gel-based proteomics and immunohistochemistry analysis and that antibodies against this protein can identify IACs in an unbiased manner in a large breast cancer tissue microarray making them potentially useful as a diagnostic aid.

An Unusual Apocrine Carcinoma on the Forehead

We herein report an unusual case of apocrine carcinoma on the forehead. The lesion was formed by the anastomosis of numerous tubular structures with widespread decapitation secretion, thus demonstrating apocrine differentiation. However, we observed some unusual histopathologic features that differed from those found in typical examples of apocrine ductal carcinoma, namely: 1) a relatively well-circumscribed lesion in the dermis, and 2) nodular or solid aggregations composed of basaloid cells. We believe the present case is an apocrine ductal carcinoma, although it has a nodular appearance and basaloid cells. Otherwise, it could be a hitherto undescribed variant of apocrine carcinoma. This apocrine carcinoma on the forehead may have originated from either pluripotential cells or from apocrine glands at an unusual site.

E-cadherin immunohistochemical analysis of histiocytoid carcinoma of the breast.

Histiocytoid carcinoma is a rare type of invasive breast carcinoma. It has been considered to be a variant of lobular carcinoma, a variant of apocrine ductal carcinoma, and an apocrine variant of lobular carcinoma and to resemble lipid-rich carcinoma. In attempts to elucidate its histogenesis, investigators have used mucin and oil red O histochemical analysis and GCDFP-15 immunostaining. E-cadherin is a relatively recent addition to the armamentarium of immunohistochemical markers used for cell differentiation and is a member of a family of transmembrane glycoproteins that has been shown to have a strong correlation with the histologic phenotypes of breast carcinoma. Most ductal carcinomas show diffuse membrane expression of E-cadherin, and lobular carcinomas are characterized by complete lack of membrane staining of E-cadherin. The object of this study was to use E-cadherin immunohistochemical analysis to help clarify the histogenesis of histiocytoid carcinoma. Fourteen cases containing the diagnosis of histiocytoid carcinoma of the breast were identified at M. D. Anderson Cancer Center (Houston, TX) from 1988 to 2001. All cases were rereviewed, histologic features were evaluated, and immunohistochemical staining with E-cadherin and GCDFP-15 was performed. Clinical information was extracted from the patients' medical records. Eleven cases met published histologic criteria for histiocytoid carcinoma. The remaining three cases were apocrine carcinoma. The pattern of tumor infiltration was solid, without secondary lumen formation in all cases of histiocytoid carcinoma. Lobular carcinoma in situ was identified in eight cases, but was absent in three. There was no E-cadherin immunohistochemical staining in eight of the 11 cases of histiocytoid carcinoma (72.7%). GCDFP-15 was immunoreactive in all 10 cases of histiocytoid carcinoma where it was performed. Follow-up data was available for nine of the 11 cases of histiocytoid carcinoma: six patients were alive with disease at 1.5 to 48 months, one patient had died of disease at 60 months, and two patients had no evidence of disease at 32 and 45 months. We conclude that histiocytoid carcinoma has an immunophenotypical profile consistent with both ductal and lobular differentiation. Moreover, the lack of consistent morphologic features, a specific clinical profile, and a distinct immunohistochemical pattern lead us to hypothesize that histiocytoid carcinoma is not a special type of breast cancer.

Apocrine ductal carcinoma in situ of the breast: Histologic classification and expression of biologic markers

Apocrine ductal carcinoma in situ (ADCIS) has been called a special type of ductal carcinoma in situ (DCIS) because the histologic grading is considered difficult using the classification schemes that have been proposed for common DCIS. However, ADCIS encompasses a spectrum of lesions with different morphologic aspects ranging from minimally atypical to overtly malignant. To define a classification scheme for ADCIS, 35 cases (22 pure and 13 associated with invasive carcinoma) were selected on the basis of conventional morphology on hematoxylin and eosin (H&E)-stained sections. Each case was assigned to 1 of 3 histologic grades (low, intermediate, and high) based on nuclear morphology and the presence of necrosis. In addition, the expression of hormone receptors p53, bcl-2, c-erbB-2, and Ki-67 was evaluated by immunohistochemistry, and the DNA ploidy was determined by image cytometry. Fifteen cases were classified as high histologic grade, 10 as low histologic grade, and the other 10 as intermediate grade. All but 4 cases, irrespective of grade, had the same hormonal immunophenotype: androgen receptor positivity (97.1%) and estrogen receptor and progesterone receptor negativity (94.3% and 97.1% respectively). Twenty-one cases (61.8%) showed p53 expression, and 47.1% of the cases were positive for c-erbB-2. The median positivity for Ki-67 was 5.2%. ADCIS has a unique morphologic and hormonal profile, distinct from common DCIS, deserving a specific classification. The proposed classification scheme allows for categorization of ADCIS according to the most important morphologic features already seen in common DCIS, ie, nuclear grade and necrosis. The expression of biologic markers other than hormonal receptors and bcl2 in ADCIS seems in general to be similar to that in common DCIS. Ki-67 and c-erbB-2 are expressed more frequently in intermediate and high histologic grade ADCIS. HUM PATHOL 32:487-493. Copyright © 2001 by W.B. Saunders Company

Molecular Cytogenetic Comparison of Apocrine Hyperplasia and Apocrine Carcinoma of the Breast

The relationship of apocrine metaplasia to invasive breast cancer is controversial. Different authors have reported that apocrine differentiation in proliferative lesions may be a risk factor, a precursor lesion, or have no association with malignancy. The aim of this study was to compare the genetic alterations in benign apocrine hyperplasia with apocrine ductal carcinoma in situ (DCIS) and invasive apocrine carcinomas of the breast using comparative genomic hybridization. The mean number of alterations in apocrine hyperplasia was 4.1 (n = 10) compared to 10.2 in apocrine DCIS (n = 10) and 14.8 (n = 4) in invasive carcinoma. The most common alterations in apocrine hyperplasia were gains of 2q, 13q, and 1p and losses of 1p, 17q, 22q, 2p, 10q, and 16q. Apocrine DCIS and invasive carcinomas showed gains of 1q, 2q, 1p, and losses of 1p, 22q, 17q, 12q, and 16q as their most common DNA copy number changes. Apocrine hyperplasia is considered to be a benign lesion and its relationship to invasive carcinoma remains unclear. Our data suggest that some apocrine hyperplasias may be clonal proliferations. The mean number of alterations are lower in apocrine hyperplasia, however the changes show considerable overlap with those identified in in situ and invasive apocrine carcinoma. These alterations are also commonly seen in nonapocrine breast cancer. The data are consistent with apocrine hyperplasia as a putative nonobligate precursor of apocrine carcinoma.