633 Background: Most invasive breast cancers are associated with more than one histologic subtype of DIN. The clinical and biologic significance of these DIN subtypes is under-appreciated. Methods: We reviewed 853 cases of DIN diagnosed... more
633 Background: Most invasive breast cancers are associated with more than one histologic subtype of DIN. The clinical and biologic significance of these DIN subtypes is under-appreciated. Methods: We reviewed 853 cases of DIN diagnosed at our University based Breast Center between 2003 and 2008, 568 (67%) of which were associated with an invasive cancer. Cases of pure invasive cancer without DIN were excluded. Results: A single histologic subtype was present in 41% of the cases, two subtypes in 43%, and three in 16%. The most common DIN subtypes present were solid (52%) and cribriform (50%), while the comedo (18%), micropapillary (11%), papillary (9%) and flat (6%) subtypes were less common. Comedo and solid DIN were frequently found together (Odds ratio [OR]) for coexpression 1.94, p< .001) as were micropapillary and papillary subtypes (OR 2.58, p< .005). Comedo DIN was much less likely to be found with papillary (OR .24, p< .005), flat (OR .34, p< .05), cribriform (OR .42, p< .001) or micropapillary (OR .48, p< .05) subtypes. We also examined multiple biological parameters and their association with the different DIN subtypes as shown in the table below. Solid and comedo subtypes tend to be hormone receptor negative, Her2 positive and high grade while the cribriform subtype tends to be hormone receptor positive, Her2 negative and low grade. Papillary and comedo DIN are most likely to be larger lesions. Papillary DIN is least likely to be associated with an invasive cancer. Conclusions: The histologic architecture provides clues to the underlying molecular changes and biological behavior of DIN. This study will begin to help us understand the molecular basis for the different histologic subtypes of DIN, their different clinical behaviors and tendencies to progress to invasive cancer. [Table: see text] No significant financial relationships to disclose.
Research Interests:
Research Interests: Risk, Medicine, Humans, Female, Breast, and 3 moreHyperplasia, Precancerous Conditions, and Breast Neoplasms
Research Interests:
Tienda online donde Comprar Tumors of the mammary gland. AFIP Atlas of tumor pathology series 4, Vol. 10 al precio 200,96 € de Fattaneh Tavassoli, tienda de Libros de Medicina, Libros de Patologia - Patologia
Research Interests:
Research Interests:
Research Interests:
Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive... more
Triple negative breast carcinomas (TNBC) do not benefit from hormonal or Herceptin therapies. In search of novel therapeutic targets for TNBC, interest is escalating in a subset of these tumors that are androgen receptor (AR) positive with potential benefit from anti-androgen therapy. Against this background, the frequency of AR expression alone and in combination with other markers and morphologic features was assessed to identify TNBC subtypes for targeted therapy. 400 consecutive invasive mammary carcinomas with known estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and HER2 status were selected for study. The frequency of AR positivity alone or in combination with other markers was recorded with specific attention to the morphology of AR+ TNBCs. Ki67 was evaluated in selected group of cases. ASCO/CAP guidelines were used for interpretation of the various biomarkers. Of the 400 tumors, 32 (8%) carcinomas were quadruple negative (ER-, PR-, AR-, Her2-), wh...
Research Interests:
Local chest wall relapse following mastectomy for ductal carcinoma in situ (DCIS) is an unusual event. We report on 10 cases of patients treated with mastectomy for DCIS who subsequently experienced a chest wall relapse as the first site... more
Local chest wall relapse following mastectomy for ductal carcinoma in situ (DCIS) is an unusual event. We report on 10 cases of patients treated with mastectomy for DCIS who subsequently experienced a chest wall relapse as the first site of recurrence. To our knowledge, this is the largest reported collection of postmastectomy chest wall relapses for DCIS. The tumor registry and medical records from Yale-New Haven Hospital of all patients treated for ductal carcinoma in situ were reviewed. Individual records and radiation therapy charts of those patients sustaining a chest wall relapse following mastectomy were reviewed in detail. All pathology from the original mastectomy, as well as from the chest wall relapse, was re-reviewed by the pathologist. All chest wall relapses were treated with radiation therapy, with or without adjuvant systemic therapy. Of the 10 cases, 9 patients remain alive without evidence of disease. Young patient age, multiquadrant disease, and the presence of re...
Research Interests:
Objective.—To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen... more
Objective.—To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) and protein pS2 in 33 cases. Methods.—The morphologic and immunohistochemical findings were correlated to patient menstrual status, which was categorized as childbearing age (n = 15), perimenopausal (n = 8), and postmenopausal (n = 10). Results.—Fibromatoses in women of childbearing age were more cellular, more mitotically active, and displayed a larger proportion of cells with mild atypia than those in perimenopausal and postmenopausal women. The hormonal status of these 3 groups does not explain the morphologic variations observed in these groups, inasmuch as no immunostaining for any of the hormone receptors was detected in the tumors. Conclusions.—The absence of estrogen receptor and pS2 in breast fibromatoses suggests that antiestrogenic agen...
In this study, the pattern of distribution of the nuclei immunoreactive with Ki67 was examined in DIN1c (DCIS, grade 1/low grade), DIN2 (DCIS, grade 2/intermediate grade), and DIN3 (DCIS, grade 3/high grade). The lesions were evaluated to... more
In this study, the pattern of distribution of the nuclei immunoreactive with Ki67 was examined in DIN1c (DCIS, grade 1/low grade), DIN2 (DCIS, grade 2/intermediate grade), and DIN3 (DCIS, grade 3/high grade). The lesions were evaluated to determine if distinctive patterns could be identified in correlation with lesion grade. Fifty seven (n=57) consecutive DIN cases were investigated. Of these, 15 qualified as DIN1c, 28 as DIN2 and 14 as DIN3. The patterns of distribution were recorded for each case as either basal/peripheral or haphazard within the epithelial proliferation. There was a statistically significant difference between the DIN1c, DIN2 and DIN3 in terms of basal/peripheral versus haphazard distribution of Ki67 immunostaining (Chi-square test, P<0.0001). Basal/peripheral staining pattern was dominant among the DIN1c cases, while haphazard staining pattern was the dominant distribution among the DIN3 cases. One half of the DIN2 cases showed basal/peripheral staining patte...
Research Interests:
In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10-20 % of the patients develop a recurrence, about 50 % of which are invasive. Prior studies have shown that... more
In the USA alone, approximately 61,000 new diagnoses of ductal intraepithelial neoplasia 1c-3 (DIN) are made each year. Around 10-20 % of the patients develop a recurrence, about 50 % of which are invasive. Prior studies have shown that invasive breast carcinomas positive for p16 or p53 have a higher frequency of recurrence and a more aggressive course; however, the co-expression of these markers across the entire spectrum of DIN and its potential correlation with grade of the lesions has not been studied previously. Immunohistochemical staining for p16 and p53 was evaluated on 262 DIN lesions from 211 cases diagnosed between 1991 and 2008. The lesions ranged from DIN1b (atypical intraductal hyperplasia) to DIN3 (DCIS, grade 3) and included 45 cases with associated invasive carcinoma. Frequency of staining for both p16 and p53 increased with increasing grade of DIN. Strong co-expression was found exclusively in higher grade DIN lesions (DIN2 and DIN3) particularly those associated w...
Research Interests:
A 41-year-old female presented for diagnostic baseline mammogram for a palpable breast mass which she first noticed 6 months ago. She did not have any other clinical symptoms. Digital breast tomosynthesis along with 2D synthesized imaging... more
A 41-year-old female presented for diagnostic baseline mammogram for a palpable breast mass which she first noticed 6 months ago. She did not have any other clinical symptoms. Digital breast tomosynthesis along with 2D synthesized imaging and targeted ultrasound showed a heterogeneous lobulated mass versus a conglomerate of three contiguous masses in the right breast at the 10–11 o’clock position middle depth which correlated with the palpable lesion (Fig. 1). Findings were suspicious for multicentric breast cancer. Ultrasound guided biopsy was performed of the dominant component of the mass. Pathology review of the biopsy was interpreted as an intramammary lymph node with reactive changes which was thought to be discordant. The decision was made to surgically remove the discordant area. An ultrasound guided wire localization was performed using two wires to bracket the area in the right breast at the 10 o’clock position (Fig. 2). The gross pathologic specimen was received en bloc
Research Interests:
Benign apocrine metaplasia (AM) of the adult breast is a very common, but enigmatic lesion. It has been speculated that AM might be a precursor of malignancy or an indicator of a susceptibility of the breast tissue to develop neoplasia,... more
Benign apocrine metaplasia (AM) of the adult breast is a very common, but enigmatic lesion. It has been speculated that AM might be a precursor of malignancy or an indicator of a susceptibility of the breast tissue to develop neoplasia, mainly based on comparing the frequency of AM in breast cancer and non-breast cancer patients [1]. Studies using comparative genomic hybridization have supported this by showing similar molecular alterations in benign and malignant apocrine lesions [2]. Few studies, however, have compared expression of biomarkers involved in tumor progression in AM and progressively more advanced atypical apocrine lesions. The expression of C-KIT, COX2, CD24, and CD44s was evaluated by immunohistochemistry in formalin-fixed, paraffin-embedded material of 9 AM, 20 apocrine ductal intraepithelial neoplasia (DIN1c-3) and 40 atypical apocrine lesions (not qualifying for DIN1c-3) and compared to expression of the same biomarkers in adjacent normal ductal epithelium. Of the 66 apocrine lesions, 62 (94 %) did not express C-KIT compared to 4/63 (6 %) of the normal glands (Fisher&amp;amp;amp;amp;amp;amp;amp;amp;#39;s exact, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). COX2 was expressed in a significantly higher proportion of apocrine lesions than of normal glands (49 vs. 14 %, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), and the number of apocrine lesions positive for CD24 was found to be higher with increasing aggressiveness of the lesions (Spearman, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). In conclusion, benign and non-invasive proliferative apocrine lesions of the breast display immuno-phenotypical characteristics previously ascribed mainly to malignant transformation. This could lend support to the theory that AM is an early step towards malignant transformation, albeit associated with slow progression to carcinoma.
Research Interests:
OBJECTIVE: To review the literature on brain metastasis (BM) from ovarian cancer, and assess the frequency, anatomical, clinical and paraclinical information and factors associated with prognosis. BACKGROUND: Ovarian cancer is a rare... more
OBJECTIVE: To review the literature on brain metastasis (BM) from ovarian cancer, and assess the frequency, anatomical, clinical and paraclinical information and factors associated with prognosis. BACKGROUND: Ovarian cancer is a rare cause of brain metastasis. Progressive neurologic disability often results and the prognosis is generally poor. A comprehensive review on this subject has not been published previously. DESIGN/METHODS: This systematic literature search used the Pubmed and Yale library search engine and included all relevant articles in English literature. A total of 66 publications were found, 57 of which were used representing 591 patients with BM from ovarian cancer. RESULTS: The median age of the patients was 54.3 years (range 20-81). A majority of patients (57.3%) had multiple brain lesions. The location of the lesion was cerebellar( 30%), frontal (20%), parietal (18%) and occipital (11% ) . Extracranial metastasis was present in 49.8% of cases involving liver (20.7%), lung(20.4%), lymph nodes (12.6%), bones (6.6%) and pelvic organs (4.3%). The most common symptoms were weakness (16%), seizures (11%), altered mentality (11%) visual disturbances (9%) and dizziness (8%). The interval from diagnosis of breast cancer to BM ranged from 0-133 months (median 24 ) and median survival was 8.2 months. Treatment included local radiation, surgical resection, stereotactic radiosurgery and medical therapy. Factors that significantly increased the survival were younger age at the time of ovarian cancer diagnosis and at the time of brain metastasis diagnosis, higher KPS score and multimodality treatment for the brain metastases. CONCLUSIONS: Ovarian cancer is a rare cause of brain metastasis. Development of brain metastasis among older patients and lower KPS score correlate with less favorable prognosis. The more prolonged survival after using multimodality treatment for brain metastasis is important information that can potentially impact the management of such brain metastasis in future. Study Supported by: no support Disclosure: Dr. Pakneshan has nothing to disclose. Dr. Safarpour has nothing to disclose. Dr. Tavassoli has nothing to disclose. Dr. Jabbari has received research support from Allergan Inc., Merz Pharma, and Ipsen.
Research Interests:
Research Interests:
Research Interests:
... in a Papilloma / 343 Papillary Carcinoma / 354 Noninvasive Papillary Carcinoma / 354 PupillaryIntraepithelial Neoplasia / 363 Molecular ... Introduction ol I lie Term "Lobular Neoplasia" '.7") LobularNeoplasia /... more
... in a Papilloma / 343 Papillary Carcinoma / 354 Noninvasive Papillary Carcinoma / 354 PupillaryIntraepithelial Neoplasia / 363 Molecular ... Introduction ol I lie Term "Lobular Neoplasia" '.7") LobularNeoplasia / 375 Clinical Features /375 Pathologic Features / 376 Distinction ...
Research Interests:
Research Interests:
This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer;... more
This comprehensive review provides information on epidemiology, size, grade, cerebral localization, clinical symptoms, treatments, and factors associated with longer survival in 14,599 patients with brain metastasis from breast cancer; the molecular features of breast cancers most likely to develop brain metastases and the potential use of these predictive molecular alterations for patient management and future therapeutic targets are also addressed. The review covers the data from 106 articles representing this subject in the era of modern neuroimaging (past 35 years). The incidence of brain metastasis from breast cancer (24 % in this review) is increasing due to advances in both imaging technologies leading to earlier detection of the brain metastases and introduction of novel therapies resulting in longer survival from the primary breast cancer. The mean age at the time of breast cancer and brain metastasis diagnoses was 50.3 and 48.8 years respectively. Axillary node metastasis was noted in 32.8 % of the patients who developed brain metastasis. The median time intervals between the diagnosis of breast cancer to identification of brain metastasis and from identification of brain metastasis to death were 34 and 15 months, respectively. The most common symptoms experienced in patients with brain metastasis consisted of headache (35 %), vomiting (26 %), nausea (23 %), hemiparesis (22 %), visual changes (13 %) and seizures (12 %). A majority of the patients had multiple metastases (54.2 %). Cerebellum and frontal lobes were the most common sites of metastasis (33 and 16 %, respectively). Of the primary tumors for which biomarkers were recorded, 37 % were estrogen receptor (ER)+, 41 % ER-, 36 % progesterone receptor (PR)+, 34 % PR-, 35 % human epithelial growth factor receptor 2 (HER2)+, 41 % HER2-, 27 % triple negative and 18 % triple positive (TP). Treatment in most patients consisted of a multimodality approach often with two or more of the following: whole brain radiation therapy (52 %), chemotherapy (51 %), stereotactic radiosurgery (20 %), surgical resection (14 %), trastuzumab (39 %) for HER2 positive tumors, and hormonal therapy (34 %) for ER and/or PR positive tumors. Factors that had an impact on prognosis included grade and size of the tumor, multiple metastases, presence of extra-cranial metastasis, triple negative or HER2+ biomarker status, and high Karnovsky score. Novel therapies such as application of agents to reduce tumor angiogenesis or alter permeability of the blood brain barrier are being explored with preliminary results suggesting a potential to improve survival after brain metastasis. Other potential therapies based on genetic alterations in the tumor and the microenvironment in the brain are being investigated; these are briefly discussed.
Research Interests:
Melanocytic lesions of the nipple-areolar region, whether benign or malignant, are extremely rare at any age. Only a single case of congenital melanocytic nevus of nipple has been reported from Austria in a 26-year-old male. Against this... more
Melanocytic lesions of the nipple-areolar region, whether benign or malignant, are extremely rare at any age. Only a single case of congenital melanocytic nevus of nipple has been reported from Austria in a 26-year-old male. Against this background, a congenital nevus of the nipple occurring in 5-year-old girl is described. A 5-year-old female presented with an asymptomatic, 3 9 2 mm, brown, pigmented macule on the left nipple-areolar complex. On physical examination, both breasts and axilla were otherwise unremarkable. The breasts had no evidence of any nodularity or precocious development. More than a year earlier, the patient had had a nevus excised from the back of her scalp at another institution. A biopsy of the left nipple areolar pigmented lesion (Fig. 1a and b) revealed predominantly intraepidermal and a few junctional nests of epitheloid, dyscohesive nevomelanocytes (Fig. 1c–e). These melanocytic nests were associated with focal fusion of the rete ridges (Fig. 1c and d). No pagetoid (single-cell) spread of melanocytes in the epidermis was identified. Deeper levels of the block showed extension of bland nevomelanocytic cells into the sebaceous glands (Fig. 1c, d and f). Two mammary ducts with appropriate level of development for a 5-year-old girl, and immunoreactive for CK7, were present in close proximity of smooth muscle bundles at the edge of the specimen (Fig. 1a and b), confirming the nipple-areolar location of the lesion. The nevomelanocytic cell nests were positive for S100 (Fig. 2a), Melan-A (Fig. 2b), and HMB-45 (Fig. 2c), confirming the melanocytic nature of the cells, but negative for Her2, CK7, and CD68 excluding Paget cells, Toker cells, and histiocytes, respectively. No mitotic figure was identified among the melanocytes. Ki-67 immunostain revealed no positivity in the dyscohesive nest of nevomelanocytes located either in the epidermis or in the sebaceous gland. Based on the morphologic and immunohistochemical findings, a diagnosis of congenital melanocytic nevus of nipple-areolar complex was rendered. Development of melanocytic lesions, benign or malignant, in the nipple-areolar complex is extremely rare in any age group. When this possibility is suggested on the basis of morphology and particularly in patients over 20 years of age, it is important to exclude pigmented histiocytes (melanophages) and Paget cells by using appropriate immunostains— CD68, and CK7/Her2 immunohistochemistry—respectively. Thorough examination of multiple deeper H&E sections to identify bland nevomelanocytes, which are positive for S100, Melan-A, and HMB-45, in the sebaceous lobules or peripheral nerve twigs could provide ironclad evidence for a congenital nevus, and is useful in avoiding diagnostic pitfalls such as melanoma. Primary melanomas are extremely rare in the nipple-areolar region, with only 22 cases reported in the literature since 1947. Address correspondence and reprint requests to: Fattaneh A. Tavassoli, MD, Professor, Department of Pathology, Yale University School of Medicine, PO Box 208023, New Haven, CT 06520-8023, USA, or e-mail: fattaneh. tavassoli@yale.edu
Research Interests: Psychology, Medicine, Humans, Female, Skin Neoplasms, and 3 moreChild preschool, The Breast, and Nipples
Interpretation of papillary lesions of the breast remains a challenging task because of the wide morphologic spectrum encountered in the benign, atypical, and malignant subtypes. Data on clinical significance and outcome of papillary... more
Interpretation of papillary lesions of the breast remains a challenging task because of the wide morphologic spectrum encountered in the benign, atypical, and malignant subtypes. Data on clinical significance and outcome of papillary lesions, with superimposed atypia or areas similar to ductal carcinoma in situ partially replacing the benign elements, are sparse. Furthermore, complete excision of even a fully developed papillary carcinoma confined to a dilated or cystic duct is associated with an excellent prognosis, whereas a complex papilloma extending into multiple branches of a duct may ultimately recur as a carcinoma because of incomplete excision of microscopic foci. This makes an outcome-based classification difficult. An arbitrary yet practical approach to classification is outlined, with discussion of methods to circumvent the various diagnostic difficulties. The limitations in precise diagnosis of papillary lesions in aspirates are addressed, and the implications of findin...
Research Interests:
Secretory changes that occurred in the breasts of 32 women who were not pregnant or lactating were reviewed. These changes took two forms, with partial or complete involvement of one or more lobules. The more frequently occurring focal... more
Secretory changes that occurred in the breasts of 32 women who were not pregnant or lactating were reviewed. These changes took two forms, with partial or complete involvement of one or more lobules. The more frequently occurring focal lactating effect was observed in 23 patients. The second form, a marked clearing of the cytoplasm within acinar cells, occurred in nine patients. Both patterns were present simultaneously in 2 of the 32 patients. Hormonal, anti-psychotic, and anti-hypertensive medications appear to correlate with the lactational change.
Research Interests:
Resected uteri from a series of 48 consecutive patients with atypical endometrial hyperplasia ("carcinoma in situ") identified in curettings were studied to determine the frequency of associated adenocarcinoma. Thirty-nine of... more
Resected uteri from a series of 48 consecutive patients with atypical endometrial hyperplasia ("carcinoma in situ") identified in curettings were studied to determine the frequency of associated adenocarcinoma. Thirty-nine of the women had received estrogen or oral contraceptives. Twelve uteri (25%) contained small superficial foci interpreted as well differentiated adenocarcinoma. Consideration of this observation together with the absence of adenocarcinoma in the extensive experience reported in other studies of women with atypical hyperplasia treated with progestogens alone shows a deficit of patients with progression to invasive carcinoma. We reconcile this apparent conflict with the hypothesis that lesions classified as focal well-differentiated endometrial adenocarcinoma occurring with atypical hyperplasia in perimenopausal women exposed to estrogen are common and are consistently reversed by progestogen therapy.
Research Interests:
Myoepithelial carcinoma (MEC) is a rare type of breast cancer composed purely of myoepithelial cells. Most often it presents with a spindle cell morphology that can mimic several benign and malignant lesions and may be misdiagnosed by the... more
Myoepithelial carcinoma (MEC) is a rare type of breast cancer composed purely of myoepithelial cells. Most often it presents with a spindle cell morphology that can mimic several benign and malignant lesions and may be misdiagnosed by the pathologist. We report 15 cases of MEC, which were sent to our consultation practice: Five of them were initially diagnosed as benign. The patients, all female, ranged from 45 to 86 years in age (mean 69.5) and-with one exception-presented with a breast mass. The tumor size measured between 1 and 4.8 cm (mean 2.6 cm). Microscopically, the tumors had infiltrative growth pattern most frequently with thin anastomosing cords of tumor cells associated with an intimately admixed reactive spindle cell stroma. The neoplastic myoepithelial cells were emanating from the myoepithelial cell layer of entrapped ductules in every case. The nuclei showed mild to moderate pleomorphism, and the mitotic activity ranged from 0 to 9/10 high power field. Immunohistochemical stains for p63, CD10, CK903, and CK5/6 reacted strongly and diffusely with the tumor cells, and mainly the reactive stroma had weak positivity for calponin, S-100, and smooth muscle actin. Estrogen receptor, progesteron receptor, and Her2 immunostains were negative, but strong epidermal growth factor receptor expression was observed. Follow-up was available for seven patients: All of them were alive at last contact; one patient had local recurrence, and one developed pulmonary metastases. MEC is a potentially aggressive malignant neoplasm sharing many features with metaplastic carcinomas. Morphologically, it is often difficult to distinguish it from benign spindle cell proliferations.
Research Interests:
The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions... more
The clinicopathological features of central intraductal papillomas of the breast presenting with florid usual ductal hyperplasia or atypical ductal hyperplasia (ADH) were analyzed in a retrospective series of 119 patients, whose lesions were sent to the Armed Forces Institute of Pathology from 1976 to 1990. After histological review considering predefined morphological and quantitative criteria, the 119 central papillomas were classified into 22 papillomas with florid usual ductal hyperplasia (18%), 40 papillomas with focal atypia (34%), 24 atypical papillomas (20%) and 33 carcinomas arising in a papilloma (28%). After a median period of follow-up of 110 months, 16 recurrences (5 papillomas, 2 carcinomas arising in a papilloma, 4 ductal carcinomas in situ, 5 invasive carcinomas) occurred. No statistically significant difference was observed in relation to recurrence for the various categories of papillomas. The presence of epithelial hyperplasia, ADH or lobular neoplasia in the surrounding breast as well as infarction of the papilloma were significant predictive factors of recurrence ( P=0.02 and P=0.005, respectively, log-rank test). The main reason for the observed low rate of significant recurrences in this series was that epithelial atypia (whether comprising 20% or 60% of the papillary lesion) was, in most of the cases, localized in a confined lesion that was completely excised.
Research Interests:
Intranuclear helioid bodies were identified by light microscopy in eight cases of mammary intraductal hyperplasia, only one of which was atypical. These structures appear as round, intranuclear eosinophilic bodies on light microscopic... more
Intranuclear helioid bodies were identified by light microscopy in eight cases of mammary intraductal hyperplasia, only one of which was atypical. These structures appear as round, intranuclear eosinophilic bodies on light microscopic examination. When prominent, they may be and have been mistaken for viral inclusions. Ultrastructural analysis of these inclusions shows a single-membrane-bound structure containing a laminated or homogeneously electron-dense core with a corona of radiating filaments. In the first and only previous report of this structure in the breast, helioid bodies were identified incidentally during an ultrastructural analysis of a breast adenoma, but the light microscopic counterpart of this structure was not described or illustrated. In view of the similarity of the laminated inclusions to psammoma bodies, the possibility that helioid bodies serve as a nidus for development of microcalcification in the breast was considered. Actual microcalcification was not evident in the vicinity of any of these inclusions, however, and there was no evidence of calcification in these structures on von Kossa&#39;s stain for calcium.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Research Interests: Histology, Clinical Biochemistry, Molecular Genetics, Adolescent, Apoptosis, and 15 moreMedicine, Molecular Diagnostics, In Situ Hybridization, Clinical Chemistry, Cytogenetics, Humans, Female, Aged, Middle Aged, Adult, Biological markers, Immunophenotyping, Breast Neoplasms, Medical and Health Sciences, and Modern Pathology
It is often difficult to make a diagnosis of carcinoma in endometrial biopsies and curettings that show proliferative mucinous lesions because of the deceptively bland appearance of invasive mucinous adenocarcinoma at this site. Only... more
It is often difficult to make a diagnosis of carcinoma in endometrial biopsies and curettings that show proliferative mucinous lesions because of the deceptively bland appearance of invasive mucinous adenocarcinoma at this site. Only limited information is available regarding criteria for distinguishing mucinous carcinoma from atypical mucinous proliferations and mucinous metaplasia of the endometrium. The threshold for diagnosing mucinous carcinoma in endometrial biopsies/ curettings may possibly be lower than that for endometrioid carcinoma. We evaluated different sets of existing criteria in order to determine which best facilitate a diagnosis of carcinoma in endometrial biopsies/curettings containing mucinous lesions. The biopsy/ curetting samples with the corresponding uterus (hysterectomy performed within 6.5 months) from each of 31 patients were studied. The biopsies/curettings were assessed with previously published criteria that more typically are used for endometrioid prol...
Research Interests:
Characterized by a solid proliferation of generally small, loosely cohesive cells in the terminal duct-lobular units, lobular intraepithelial neoplasia was first described in detail by Foote and Stewart in the 1940s, who designated it as... more
Characterized by a solid proliferation of generally small, loosely cohesive cells in the terminal duct-lobular units, lobular intraepithelial neoplasia was first described in detail by Foote and Stewart in the 1940s, who designated it as lobular carcinoma in situ. It was noted at the time that this lesion is most often an incidental finding, multicentric and often bilateral process. Shortly after this original description, these proliferations were subdivided into atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS); mastectomy was the treatment recommended for the latter and no therapy was deemed necessary for ALH. The criteria for separation of ALH from LCIS varied significantly from one institution to another. At a time when mastectomy was the main treatment for anything designated as carcinoma in situ, one major reason for introduction of ALH was undoubtedly to prevent mastectomy for the more limited versions of the lesion.
Research Interests:
The morphologically and biologically diverse types of breast carcinomas are currently classified and managed on the basis of a number of clinically validated clinicopathologic factors that are used to assess prognosis, guide therapy, and... more
The morphologically and biologically diverse types of breast carcinomas are currently classified and managed on the basis of a number of clinically validated clinicopathologic factors that are used to assess prognosis, guide therapy, and predict response to therapy. These factors include patient age and menopausal status, tumor type, size and grade, lymphovascular involvement, nodal status, and status of various markers such as estrogen receptor (ER), progesterone receptor (PR), and Her2. Based on these prognostic and predictive markers, the patients will receive local or systemic therapy—radiation or chemotherapy—with or without hormonal or trastuzumab therapy. Predicting the prognosis and metastatic potential of carcinomas at the time of detection is a major challenge in the current management of patients with breast carcinoma. One major criticism of our current approach is that it does not accurately predict outcome for individual patients. For example, morphologically similar tumors with identical immunoprofiles may respond differently to the same therapy. Furthermore, approximately 15% of the carcinomas categorized as low grade and with a low risk of aggressive behavior (based on a tumor size of <1 cm, node negativity, ER and/or PR positivity, low grade and postmenopausal status) will recur. One potential reason for the 15% divergence from anticipated behavior may be the lack of veritable standardization in assessment of all currently used predictive and prognostic factors. Another criticism is that despite many years of using a morphologic and functional approach to the classification of breast carcinomas, some variants remained “undiscovered” until recently. Among the recently discovered variants are the various metaplastic and myoepithelial derived carcinomas. One wonders whether these truly reflect the discovery of new variants of breast carcinoma induced by some novel environmental influence or whether these lesions were always around and simply ignored in our efforts to pigeon-hole them into known and well-recognized categories of breast carcinoma. I suspect additional morphologic variants of breast carcinoma will be “discovered.” The introduction of immunohistochemistry has been extremely helpful in refining and “purifying” some of the categories. Gene Expression Profiling of Breast Carcinomas
Research Interests:
Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen receptor—positive breast cancer, which is expressed as the recurrence score (RS). Studies have shown that patients with a high-risk RS will most likely benefit... more
Oncotype DX is a 21-gene assay that quantifies the recurrence risk in estrogen receptor—positive breast cancer, which is expressed as the recurrence score (RS). Studies have shown that patients with a high-risk RS will most likely benefit from adjuvant chemotherapy, but there is no proven advantage for patients with a low-risk RS who still face an average recurrence risk of 7%. In this study, the relationship between the RS and the cell cycle—related antigen Ki-67 was assessed in 32 breast carcinomas and evaluated for a potential association. Comparison of the RS with tumor type, grade, and the Ki-67 proliferation index (PI) revealed an overall concordance. However, some tumors with a low RS revealed a surprisingly high Ki-67 PI. These cases may correspond to the 7% of low-risk RS carcinomas that recur. Therefore, the authors propose a combined evaluation of the RS and Ki-67 PI to identify tumors with high recurrence potential from the low-risk and intermediate-risk RS groups.
Research Interests: Breast Cancer, Cell Cycle, Immunohistochemistry, Estrogen Receptor, Humans, and 15 moreFemale, Surgical Pathology, Clinical Sciences, Middle Aged, Adult, Breast carcinoma, Cell Proliferation, Low Risk, Predictive value of tests, Adjuvant Chemotherapy, Adenocarcinoma, Gene expression profiling, Lymph nodes, Breast Neoplasms, and High risk
Seventeen cases of papillary endothelial hyperplasia (PEH, Masson&#39;s vegetant intravascular hemangioendothelioma) involving breast or mammary subcutaneous tissues are described. The mean patient age was 59; 14 (82%) were female and... more
Seventeen cases of papillary endothelial hyperplasia (PEH, Masson&#39;s vegetant intravascular hemangioendothelioma) involving breast or mammary subcutaneous tissues are described. The mean patient age was 59; 14 (82%) were female and 12 (71%) presented with a mass. Nine women had mammographic evaluation, 3 of whom had microcalcifications. Five neoplasms were discovered by routine mammography. Sixteen cases were 2.7 cm or less in greatest dimension, and 8 (47%) were associated with a thrombus and/or cavernous hemangioma. Follow-up in 10 cases (up to nearly 8 years) showed no recurrences. Fifty-nine percent of the cases were received at AFIP for consultation with a working diagnosis of angiosarcoma. Features that help distinguish PEH from angiosarcoma include circumscription of the lesion, location in a vessel or association with thrombus, and papillary architecture without significant cytologic atypia or areas of solid growth. The recognition of the morphologic features of this lesion and its inclusion in the differential diagnosis of vascular mammary tumors will reduce the likelihood of its misdiagnosis as an angiosarcoma and avoid unnecessary and aggressive therapy.
Research Interests:
Summary The morphologic features of 15 uterine plexiform tumorlets are described. Four of the 15 were examined ultrastructurally; all of these showed features of smooth muscle differentiation. Thus, origin from smooth muscle cells is most... more
Summary The morphologic features of 15 uterine plexiform tumorlets are described. Four of the 15 were examined ultrastructurally; all of these showed features of smooth muscle differentiation. Thus, origin from smooth muscle cells is most likely.
Research Interests:
Peritoneal leiomyomatosis (PL) occurs in women of reproductive age. Of 20 women with PL in this study, 10 were pregnant or immediately postpartum, and 7 were taking oral contraceptive steroids. Only three of the 20 women were not pregnant... more
Peritoneal leiomyomatosis (PL) occurs in women of reproductive age. Of 20 women with PL in this study, 10 were pregnant or immediately postpartum, and 7 were taking oral contraceptive steroids. Only three of the 20 women were not pregnant or taking exogenous hormones. All PL nodules were composed mainly of spindle cells, but decidual cells were admixed with the spindle cells in some of the nodules in six of the 10 pregnant and postpartum women. Electron microscopy was applied to the nodules from six women representing the three different hormonal backgrounds. All contained smooth muscle cells. One was composed exclusively of smooth muscle cells, while four of the six contained smooth muscle cells predominantly but were admixed with myofibroblasts or altered smooth muscle cells and fibroblasts. Decidual cells were conspicuous in the nodules examined ultrastructurally from a pregnant woman. Despite incomplete excisions, none of the 14 women with follow-up had progressive disease. Complete or partial regression of PL was verified by &quot;second-look&quot; laparotomy in four women, but a repeat cesarian section in a fifth woman revealed persistence (or recurrence) of PL 1.5 years after the initial diagnosis. PL probably results from an unusual predisposition, or selective sensitivity, of subperitoneal mesenchymal stem cells in some women to undergo metaplasia and differentiation to smooth muscle, fibroblasts, myofibroblasts, and decidual cells. In the majority of women, hormonal stimulation is an initiator or promoter of the process.
Research Interests:
Research Interests:
Research Interests:
Research Interests:
Endometrial adenocarcinoma associated with pregnancy is a rare lesion; only 14 acceptable examples have been reported in the literature. This study describes five additional examples with a critical review of the previously published... more
Endometrial adenocarcinoma associated with pregnancy is a rare lesion; only 14 acceptable examples have been reported in the literature. This study describes five additional examples with a critical review of the previously published cases. Four of the five women were nulliparous and three had sought medical intervention for infertility. The tumors were all well-differentiated endometrioid adenocarcinomas; three had a focal to extensive papillary pattern and three had focal to extensive squamous differentiation. Four were diagnosed at the time of dilatation and curettage and one at the time of cesarean section for a 28-week, live infant. Follow-up was available for four of the five women. Two women underwent hysterectomy with bilateral oophorectomy and were alive and well 12 and 48 months after diagnosis. The woman who had the live birth and the remaining woman were treated by repeat curettage with or without progesterone therapy, and each woman has had two subsequent full-term pregnancies with live births. These women are alive and well 57 and 58 months after diagnosis. Women with focal, well-differentiated carcinomas can successfully maintain their fertility if followed by repeat curettage with or without progesterone therapy.
Research Interests:
ABSTRACT The cytological and histological findings of a case of breast carcinoma with osteoclast-like giant cells are presented. A fine needle aspiration specimen demonstrated the characteristic combination of malignant epithelium and... more
ABSTRACT The cytological and histological findings of a case of breast carcinoma with osteoclast-like giant cells are presented. A fine needle aspiration specimen demonstrated the characteristic combination of malignant epithelium and reactive multinucleated cells and enabled identification of this rare variant of breast cancer. Immunocytochemical studies using the monoclonal antibody KP1[CD68] support a histiocytic origin for the osteoclast-like cells.
Research Interests:
The natural history of patients with intraductal carcinoma (DCIS) and microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous... more
The natural history of patients with intraductal carcinoma (DCIS) and microinvasion is poorly defined, and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Previous studies of this lesion have used varied and/or arbitrary criteria for the evaluation of microinvasion. Thirty-eight DCIS lesions with microinvasion (n=29) or probable microinvasion (n=9), diagnosed during the period 1980-1996, were retrospectively analyzed after cases not treated with mastectomy and axillary lymph node dissection were excluded. Microinvasion was defined as a single focus of invasive carcinoma &amp;amp;lt; or = 2 mm or up to 3 foci of invasion, each &amp;amp;lt; or =1 mm in greatest dimension. The patients were all females with a mean age of 56.4 years. DCIS was of comedo (n=31) or papillary (n=7) subtype. Microinvasion was often associated with an altered, desmoplastic stroma (55%) or a lymphocytic infiltrate (39%). The foci of microinvasion ranged from 0.25 to 1.75 mm (mean, 0.6 mm), with an aggregate mean size of 1.1 mm (range, 0.25-2.25 mm). Foci of microinvasion, ranging from 1 to 3 (mean, 1.7), were adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary lymph node dissections yielded a mean of 19.3 lymph nodes (range, 7-38), and all lymph nodes were negative for metastasis. None of 33 patients, followed for a mean of 7.5 years (range, 1.0-14.4 years), developed local recurrence or metastasis. The cases of microinvasive carcinoma examined in this study, as defined above, were not associated with axillary lymph node metastases and appeared to be associated with an excellent prognosis. Further study is indicated to determine the appropriate management and long term prognosis of patients with this lesion.
Research Interests:
Myoepithelial carcinoma (MEC) is a rare type of breast cancer composed purely of myoepithelial cells. Most often it presents with a spindle cell morphology that can mimic several benign and malignant lesions and may be misdiagnosed by the... more
Myoepithelial carcinoma (MEC) is a rare type of breast cancer composed purely of myoepithelial cells. Most often it presents with a spindle cell morphology that can mimic several benign and malignant lesions and may be misdiagnosed by the pathologist. We report 15 cases of MEC, which were sent to our consultation practice: Five of them were initially diagnosed as benign. The patients, all female, ranged from 45 to 86 years in age (mean 69.5) and-with one exception-presented with a breast mass. The tumor size measured between 1 and 4.8 cm (mean 2.6 cm). Microscopically, the tumors had infiltrative growth pattern most frequently with thin anastomosing cords of tumor cells associated with an intimately admixed reactive spindle cell stroma. The neoplastic myoepithelial cells were emanating from the myoepithelial cell layer of entrapped ductules in every case. The nuclei showed mild to moderate pleomorphism, and the mitotic activity ranged from 0 to 9/10 high power field. Immunohistochemical stains for p63, CD10, CK903, and CK5/6 reacted strongly and diffusely with the tumor cells, and mainly the reactive stroma had weak positivity for calponin, S-100, and smooth muscle actin. Estrogen receptor, progesteron receptor, and Her2 immunostains were negative, but strong epidermal growth factor receptor expression was observed. Follow-up was available for seven patients: All of them were alive at last contact; one patient had local recurrence, and one developed pulmonary metastases. MEC is a potentially aggressive malignant neoplasm sharing many features with metaplastic carcinomas. Morphologically, it is often difficult to distinguish it from benign spindle cell proliferations.
Research Interests:
The presence of myoepithelial (ME) cells is considered an important feature in the vast majority of benign breast lesions. Recently, a case showing the absence of myoepithelium in a mammary duct with apocrine metaplasia was reported. To... more
The presence of myoepithelial (ME) cells is considered an important feature in the vast majority of benign breast lesions. Recently, a case showing the absence of myoepithelium in a mammary duct with apocrine metaplasia was reported. To investigate the status of ME cells associated with apocrine metaplasia, the distribution of ME cells in 59 metaplastic and intraductal proliferative apocrine lesions was evaluated using immunohistochemical expression of p63 and Calponin. p63 showed a diminished number of ME cells and increased intermyoepithelial nuclear distance in ducts with all variants of apocrine metaplasia and proliferation compared with normal glands. In the majority of cases, Calponin showed a continuous ME layer. In 6 cases, including an apocrine papilloma, there were definitive ME gaps confirmed by both markers, in the absence of atypia and with preservation of the basement membrane. In all cases, there was frequent heterogeneity in the distribution of ME cells in ducts harboring apocrine cells and even in various papillae within papillary lesions. In summary, benign and noninvasive apocrine lesions can show reduction and occasional complete loss of ME cells. This observation is particularly important when evaluating apocrine papillary proliferations, in which the absence of ME cells may lead to overdiagnosis of atypia and/or malignancy. The observation suggests that at least 2 ME markers should be used when evaluating apocrine lesions, and that a malignant diagnosis should be based on features of the proliferating cells until more data become available on the significance, if any, of the absence of ME cells in apocrine lesions.
Research Interests:
Atypical stromal cells of the lower female gynecologic tract have been specifically described in the vagina, vulva, and cervix, predominantly in the context of polyps. Rare cases of atypical stromal cells have been documented in the... more
Atypical stromal cells of the lower female gynecologic tract have been specifically described in the vagina, vulva, and cervix, predominantly in the context of polyps. Rare cases of atypical stromal cells have been documented in the endometrium. We report a series of 15 examples of atypical stromal cells in the endometrium: 13 in endometrial polyps and two within endometrial stroma in curettage/biopsy specimens unassociated with polyps. The patients ranged in age from 45 to 82 years. Immunohistochemical studies were performed to aid in the identification of the origin of these atypical cells. The differential diagnoses included adenosarcoma, endometrial stromal sarcoma, and, less likely, malignant mesodermal mixed tumor (MMMT/carcinosarcoma). Similar to atypical stromal cells reported in other gynecologic sites, such cells discovered in the endometrium also appear to have a benign clinical course after complete excision or polypectomy (follow-up ranging from 1 month to 44 months). Accurate recognition of this lesion is essential to avoid unnecessary surgical overtreatment. Because of their rarity, limited available data, and lack of significant long-term follow-up, continued clinical monitoring of these patients would be prudent.