Solitary Fibrous Tumor of Breast and Axilla: Clinicopathological Profile of Five Tumors With Comparison of Risk Stratification Models.

Introduction: Solitary fibrous tumor (SFT) is a fibroblastic tumor with malignant potential that is underpinned by a recurrent inv12(q13q13)-derived NAB2::STAT6 fusion. Breast and axilla are uncommon locations for this entity. Methods: Records of two academic institutions were electronically searched for breast and axillary SFTs. Clinical and pathologic data were reviewed. Literature review for breast or axillary SFTs was performed. Present study and previously reported tumors were stratified using five SFT risk models: original and modified Demicco metastatic risk, Salas local recurrence risk, Salas metastatic risk, and Thompson local recurrence risk. Results: Five patients with breast or axillary SFT were identified. Median age was 49 years, and median follow-up (available for four patients) was 82 months. Three patients showed no evidence of disease, and one developed recurrence. Literature review identified 58 patients with breast or axillary SFT. Median age was 54 years, and median follow-up (available for 35 patients) was 24 months. Thirty-one patients showed no evidence of disease, three developed recurrence, and one developed metastasis. Original and modified Demicco models and Thompson model showed the highest sensitivity; original and modified Demicco models and Salas metastatic risk model demonstrated the highest specificity. Kaplan-Meier models were used to assess recurrence-free probability (RFP). Original and modified Demicco models predicted RFP when stratified by "low risk" and "moderate/intermediate and high risk" tumor, though sample size was small. Conclusions: While many SFTs of breast and axilla remain indolent, a subset may develop recurrence and rarely metastasize. The modified Demicco risk model demonstrated optimal performance characteristics.

Low-grade adenosquamous carcinoma of the breast: a clinical, morphological and immunohistochemical analysis of 25 patients.

AIMS: Due to its rarity and non-specific clinical and pathological features, low-grade adenosquamous carcinoma (LGASC) of the breast continues to pose diagnostic challenges. Unlike other triple-negative breast carcinomas, LGASC tends to have an indolent clinical behaviour. It is essential to recognise this lesion for accurate diagnosis and appropriate management. METHODS AND RESULTS: Twenty-five cases of LGASC were identified in our archives and collaborating institutes. Cases of LGASC with dominant coexisting other type carcinomas were excluded. We studied the clinical presentation, morphological features, patterns of the commonly used immunohistochemical stains and follow-up. In our cohort, LGASC was commonly located at the outer aspect of the breast and associated with intraductal papilloma. The morphology of LGASC is characterised by infiltrating small glands and nests with variable squamous differentiation. We also found cuffing desmoplastic (fibrolamellar) stromal change in 75% of patients and peripheral lymphocytic aggregates in 87.5% of patients. P63 and smooth muscle myosin (SMM) were the most common myoepithelial markers used to assist in diagnosis. P63 often stained peripheral tumour cells surrounding invasive glands (circumferential staining in 80% of the cases), mimicking myoepithelial cells. It also stained the small nests with squamous differentiation. However, SMM was negative in 63% of the cases. The vast majority of our cases were triple-negative; only a few had focal and weak expressions of ER and PR. One patient who did not have excision developed lymph node metastasis. Most patients underwent excision or mastectomy with negative margins as surgical treatment; there were no recurrences or metastases in these patients with clinical follow-ups up to 108 months. CONCLUSIONS: LGASC has some unique, although not entirely specific, morphological features and immunohistochemical staining patterns. Fibrolamellar stromal change, peripheral lymphocytic aggregates and variable staining of p63 and SMM are valuable features to facilitate the diagnosis.

Re-Classification with Outcome Correlation of Previously Diagnosed Malignant Phyllodes Tumors Applying the 2016 Consensus Guidelines.

Background. Classification of phyllodes tumors is challenging due unclear diagnostic criteria, recently addressed by consensus review criteria. Herein, we reviewed all malignant phyllodes tumor resections and reclassified them based on the consensus guidelines, correlating with outcome. We hypothesize that application of criteria would result in a significant proportion being "down-graded" to either borderline or benign phyllodes tumor. Methods. Primary resections of malignant phyllodes tumor were reviewed by four AP board-certified, breast fellowship-trained pathologists. Morphologic variables delineated in consensus guidelines (ie stromal cellularity, cellular atypia, tumor border, presence of heterologous elements, presence of stromal overgrowth) were evaluated. Following review, cases were reclassified as benign, borderline, or malignant. Results. Upon reclassification, 20% (5/20) cases were "down-graded" to borderline phyllodes tumor while 80% (15/20) remained malignant phyllodes tumor. Two morphologic features were statistically significant including broadly infiltrating tumor border in 80% (12/15) of malignant phyllodes tumors compared to none in borderline phyllodes tumor (0/5) (p = 0.004) and stromal overgrowth in 67% (10/15) of malignant phyllodes tumor compared to none in borderline phyllodes tumors (0/5) (p = 0.03). Upon review of the pathology reports, 30% (6/20) contained all 5 histomorphologic variables delineated in the consensus review criteria. Malignant phyllodes tumor resulted in five cases with recurrence (33.3%, 5/15) and three cases with metastases (20.0%, 3/15) and borderline phyllodes tumor resulted in one case with recurrence (20.0%, 1/5) and no metastases (0/5). Conclusion. The consensus guidelines for phyllodes tumor are useful for subclassification. We hypothesize that standardize reporting of the histomorphologic variables may lead to better consensus.

Periductal Stromal Tumor of the Breast: One Institution's Review of 6 Tumors Over a 22 Year Period With Immunohistochemical Analysis.

Introduction. Periductal stromal tumor (PST) of the breast is a rare fibroepithelial neoplasm with controversial pathogenesis. Methods. A retrospective search of our Pathology database from 2000 to 2021 identified 6 PST, all evaluated according to the Armed Forces Institute of Pathology (AFIP) criteria. Immunohistochemistry for CD10, CD34, KIT, GATA3, p63, SOX10, ER, PR, HER2, smooth muscle actin (SMA), beta-catenin, and myogenin was performed as well. Results. All 6 patients were female and age ranged from 29 to 55 years (mean 40 years). Tumor size ranged from 2.9 to 5.9 cm (mean 3.0 cm). Data showed absence of leaf-like architecture (0/6), at least moderate hypercellularity (6/6), lack of a circumscribed border (5/6), coalescing nodules with intermixed adipose tissue (4/6), at least moderate stromal atypia (4/6), and an elevated mitotic activity ≥3mitotic figures/10 HPF (6/6). The stromal cells were positive for CD10 (4/4), CD34 (4/4), KIT (3/4), and SMA (3/4), and negative for GATA3 (0/6), p63 (0/6), SOX10 (0/6), ER (0/4), PR (0/4), HER2 (0/4), nuclear beta-catenin (0/5), and myogenin (0/4). No patient had a PST recurrence or metastasis (average follow-up of 91 months). Conclusion. We confirm that PST shares morphologic and immunophenotypic similarities with phyllodes tumor (PT). However, PST can be reliably differentiated from PT using the AFIP criteria. Additionally, PST's immunoprofile of positive KIT and CD34 stromal expression alongside the negative GATA3, p63, and SOX10 reactivity can aid the pathologist in excluding metaplastic carcinoma. All 6 of our PST behaved as benign neoplasms akin to benign PT.

Amyloid in the breast: retrospective review with clinicopathological and radiological correlation of 32 cases from a single institution.

AIMS: Mammary amyloid is an uncommon and easily overlooked pathological diagnosis with ambivalent presentation. Herein, we delineate the clinicopathological and radiographic characteristics of mammary amyloid. METHODS AND RESULTS: The Department of Pathology database was searched from 1993 to 2019 for keywords 'breast' and 'amyloid', yielding 32 cases from 23 patients, including consultation cases. All patients were female, age range = 52-81 (mean = 67.4 years). The left breast was involved more than the right (43 versus 33%, respectively); bilateral amyloid involvement was also present (24%). Amyloid was most often associated with a benign histopathological diagnosis (57%), lymphoma in 39% [all B cell lymphomas; five of nine were mucosa-associated lymphoid tissue (MALT) lymphoma] and rarely with a concurrent epithelial malignancy (invasive lobular carcinoma, 4%). Of the 14 patients with available clinical history, amyloid presented as a mass clinically or radiographically (six patients, 43%), as microcalcifications (five patients, 36%), and only occasionally as an asymmetry (14%) or fibroglandular density (7%). Microscopic examination detected microcalcifications in an additional nine cases (total 14 patients; 44% of the cohort). Interestingly, one patient had concurrent epithelial and haematological malignancy and amyloid within an axillary lymph node. Co-morbidities included autoimmune diseases and multiple myeloma. CONCLUSION: The majority of mammary amyloid cases are associated with benign histopathological findings, while imaging most frequently noted microcalcifications or mass lesions. To avoid overlooking amyloid as simply fat necrosis or fibroelastotic stromal change, a low threshold for performing ancillary stains should be considered in elderly women with benign core needle findings performed for mass lesions or microcalcifications.

Mammary mesenchymal and fibroepithelial lesions: An illustrated cytomorphologic update with differential diagnoses.

The Uniform Approach to Breast Fine Needle Aspiration Biopsy was put forward by a learned group of breast physicians in 1997. This landmark manuscript focused predominantly on diagnosis and reporting of mammary epithelial lesions. Today, most American practitioners turn initially to core biopsy rather than aspiration biopsy for the first line diagnosis of solid breast lesions; however, recent efforts from the International Academy of Cytology have produced a system called the Standardized Reporting of Breast Fine Needle Aspiration Biopsy Cytology (colloquially labeled in 2017 as the "Yokohama System"), suggesting a new interest in breast fine needle aspiration (FNA), especially in resource limited settings or clinical practice settings with experienced breast cytopathologists. Fibroepithelial lesions of the breast comprise a heterogeneous group of biphasic tumors with epithelial and stromal elements. Mesenchymal lesions of the breast include a variety of neoplasms of fibroblastic, myofibroblastic, endothelial, neural, adipocytic, muscular, and osteo-cartilaginous derivations. The cytology of mesenchymal breast lesions is infrequently described in the literature and is mainly limited to case reports and small series. This illustrated review highlights the cytologic features of fibroepithelial and mesenchymal mammary proliferations and discusses differential diagnoses and histomorphologic correlates.

Lipomatous tumors of the breast: A contemporary review.

Breast tumors with lipomatous or liposarcomatous components are infrequently encountered, but can be a source of diagnostic difficulty if the context of the fatty differentiation is not recognized. Among the true adipocytic tumors, lipoma is the most common lipomatous tumor arising in the breast. Several mammary spindle cell tumors may show adipocytic differentiation, including fibroepithelial tumors and myofibroblastoma. Liposarcomatous components most often arise in malignant phyllodes tumors, as opposed to primary liposarcomas of the breast which are believed to be uncommon. This article will review the spectrum fat-containing tumors of the breast with an emphasis on differential diagnosis and insights from recent molecular studies.

Radiation-associated angiosarcoma in the setting of breast cancer mimicking radiation dermatitis: A diagnostic pitfall.

BACKGROUND: We have encountered cases of post-radiation angiosarcoma (PRAS) histologically mimicking radiation dermatitis. METHODS: Cases of PRAS from institutional/consultation archives from 2006 to 2016 were reviewed. For inclusion, tumors had to have inapparent/subtle tumor at low magnification and scattered individual tumor cells resembling radiation fibroblasts. Prior ancillary studies were reviewed, with additional immunostains performed as needed. RESULTS: 10 cases met criteria. All occurred in women treated for breast cancer (mean age 71 years). All had similar findings: in particular, scattered single atypical cells with pleomorphic nuclei associated with microscopic hemorrhage. They also had narrow, slightly wavy "worm-like" vascular channels lined by atypical endothelial cells that lacked architectural complexity. Four cases showed focal areas of more conventional angiosarcoma. One case was an excision of a large mass that showed the "radiation dermatitis-like" pattern radiating out from the central mass. All were positive for vascular markers (CD31, CD34, and/or ERG) and MYC. MYC amplification was demonstrated by FISH in both cases tested. In 3 of 3 cases with available re-excision specimens, more obvious angiosarcoma was seen. CONCLUSIONS: PRAS can be very subtle and histologically mimic radiation dermatitis. Careful attention to histologic features and ancillary tests allow accurate diagnosis in subtle PRAS.

Does Identifying Whether Pseudoangiomatous Stromal Hyperplasia (PASH) Is Focal or Diffuse on Core Biopsy Correlate With a PASH Nodule on Excision?

AIMS: Pseudoangiomatous stromal hyperplasia (PASH) diagnosed on core needle biopsy is generally excised. As a consequence, PASH as an incidental finding, may lead to unnecessary excisions. This study categorized PASH in biopsies as diffuse versus focal to determine if this correlates with the presence of a mass. METHODS: In a 10-year period, 253 biopsies were identified and 159 met inclusion criteria. Of these, 47 biopsies had excisions. Biopsies and excisions were classified as diffuse, involving 2 adjacent lobules, or focal PASH in a single lobule or noncontiguous lobules. The diffuse or focal category on biopsy was correlated to the category on excision. Fibroadenomas with PASH were defined as concordant with diffuse PASH on biopsy. The category was correlated to the presence/absence of a mass determined from radiographic/clinical data for the 159 biopsies. RESULTS: The biopsies were classified as diffuse (105, 66%) and focal (54, 34%). A total of 67% of biopsies with focal PASH showed either focal or no PASH on excision. Diffuse PASH on biopsy, had diffuse PASH in 93% of excisions. Concordance of this classification between biopsy and excision, using a Fisher's exact test (2-tailed P value is <.0001), is statistically significant. A mass was present in 102/105 (97%) of biopsies with diffuse PASH. In biopsies with focal PASH, 78% had a mass lesion. CONCLUSIONS: Classification of diffuse versus focal PASH on biopsy was concordant with findings on excision. We found that diffuse PASH on biopsy showed strong correlation with a mass lesion. Quantifying PASH may assist with clinical-pathologic correlation and reduce unnecessary excisions.

Intracranial Cystic Myofibroblastoma: a Case Report with Literature Review.

BACKGROUND: Myofibroblastoma is a rare benign soft tissue tumor comprised of contractile myiod cells mostly in mammary gland. Only 4 prior cases arising in the central nervous system have been reported in the literature. We present a case of myofibroblastoma with a cystic component. CASE DESCRIPTION: The patient is a 76-year-old man with a history of Parkinson disease. The tumor was found incidentally after a minor fall. Magnetic resonance imaging revealed a 6.7-cm well-circumscribed, partly cystic mass with a 2.4-cm calcified central nodule located at the left sylvian fissure. The frontal dural base showed avid enhancing after gadolinium injection. Gross total resection was achieved. The tumor was marked by dense collagenous tissue and bland spindled cells in pathology review. The spindled cells demonstrated positive staining with antibodies to CD34, estrogen receptor, and smooth muscle actin. A blush of immunoreactivity is observed in scattered cells with antibody to progesterone receptor. Patient recovered well postoperatively. CONCLUSIONS: This is a rare condition of a benign soft tissue tumor of mammary gland presented primarily in the brain. The literature on myofibroblastomas arising in the central nervous system is reviewed.

Mesenchymal tumours of the breast and their mimics: a review with approach to diagnosis.

Mesenchymal tumours of the breast comprise a broad spectrum of entities that frequently pose diagnostic challenges to surgical pathologists. Metaplastic carcinoma and phyllodes tumour are site-specific mimics that account for the majority of tumours in the breast with a sarcomatoid appearance. Although uncommon, mammary tumours with fibroblastic, adipocytic or vascular differentiation may be encountered, spanning the spectrum from benign to malignant. Tumours with histiocytoid morphology are potential traps due to bland cytomorphology and resemblance to reactive processes. This comprehensive review provides a diagnostic approach to specific challenging mesenchymal tumours of the breast and their mimics, with a discussion on the salient morphological, immunohistochemical and molecular features that allow accurate diagnosis and will help the pathologist avoid potential pitfalls.

Metastatic malignant phyllodes tumor involving the cerebellum.

Brain metastases from malignant phyllodes tumors of the breast are a rare occurrence. We report a patient with a malignant phyllodes tumor of the right breast which subsequently metastasized to the right lower lobe of the lung 1 year after initial presentation, and to the right cerebellar hemisphere 2 years after diagnosis of her breast mass. After both chemotherapy and whole brain radiotherapy the patient is tumor free at most recent follow-up, 116 months after the breast tumor diagnosis was made. The literature is briefly reviewed and the differential diagnosis of malignant spindle cell brain tumors is discussed.

Dural-based Rosai-Dorfman disease: differential diagnostic considerations.

Extranodal sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) is a non-neoplastic condition that has rarely been reported to involve the central nervous system. This report documents a 28-year-old man with Rosai-Dorfman disease who presented with a seizure and a dural-based mass that was thought to represent a meningioma. Resection showed a lesion marked by large, S-100 protein immunoreactive histiocytic cells with intermixed benign lymphocytes and plasma cells. Emperipolesis with intracytoplasmic lymphocytes and plasma cells was present. Differential diagnostic considerations will be discussed.

Interobserver variability by pathologists in the distinction between cellular fibroadenomas and phyllodes tumors.

Fibroepithelial lesions with cellular stroma are frequently termed cellular fibroadenomas although criteria for distinguishing them from a phyllodes tumor are vague and subjective. However, the clinical implications and surgical management for these 2 lesions may be different. We randomly selected 21 cases of fibroepithelial lesions sent in consultation to the senior author that were challenging to classify as cellular fibroadenoma or phyllodes tumor. One to 2 representative slides of each case along with patient age were sent to 10 pathologists who specialize in breast pathology. The World Health Organization criteria for phyllodes tumors and a diagnosis form were included with the study set. For the purposes of data reporting, fibroadenoma and cellular fibroadenoma are considered together. In only 2 cases was there uniform agreement as to whether the tumor represented a fibroadenoma or phyllodes tumor. Of the remaining 19 cases, if the diagnoses of fibroadenoma and benign phyllodes tumor were combined and separated from borderline and malignant phyllodes tumors, there was 100% agreement in 53% of cases and 90% agreement in 79% of cases. This study highlights the difficulty that exists in distinguishing some cellular fibroadenomas from phyllodes tumors even for pathologists who specialize in breast pathology. However, there appears to be considerable agreement when cellular fibroadenomas and benign phyllodes tumors are distinguished from borderline and malignant phyllodes tumors. Further studies are needed to determine if there is a clinically significant difference between cellular fibroadenomas and benign phyllodes tumors and how to better distinguish them from borderline and malignant phyllodes tumors.

Mitochondria-targeted nitroxides exacerbate fluvastatin-mediated cytostatic and cytotoxic effects in breast cancer cells.

Mito-CP11, a mitochondria-targeted nitroxide formed by conjugating a triphenylphosphonium cation to a five-membered nitroxide, carboxy-proxyl (CP), has been used as a superoxide dismutase (SOD) mimetic. In this study, we investigated the antiproliferative and cytotoxic properties of submicromolar levels of Mito-CP11 alone and in combination with fluvastatin, a well known cholesterol lowering drug, in breast cancer cells. Mito-CP11, but not CP or CP plus the cationic ligand, methyl triphenylphosphonium (Me-TPP+), inhibited MCF-7 breast cancer cell proliferation. Mito-CP11 had only minimal effect on MCF-10A, non-tumorigenic mammary epithelial cells. Mito-CP11, however, significantly enhanced fluvastatin-mediated cytotoxicity in MCF-7 cells. Mito-CP11 alone and in combination with fluvastatin inhibited nuclear factor kappa-B activity mainly in MCF-7 cells. We conclude that mitochondria-targeted nitroxide antioxidant molecules (such as Mito-CP11) that are non-toxic to non-tumorigenic cells could enhance the cytostatic and cytotoxic effects of statins in breast cancer cells. This strategy of combining mitochondria-targeted non-toxic molecules with cytotoxic chemotherapeutic drugs may be successfully used to enhance the efficacy of antitumor therapies in breast cancer treatment.

Identification of novel carcinogen-mediated mammary tumor susceptibility loci in the rat using the chromosome substitution technique.

We here report the genetic basis for susceptibility and resistance to carcinogen-mediated [7,12-dimethylbenz[a]anthracene (DMBA)] mammary tumorigenesis using the full panel of SS/BN consomic rat strains, in which substitutions of individual chromosomes from the resistant BN strain onto the genomic background of the susceptible SS strain were made. Analysis of 252 consomic females identified rat mammary Quantitative Trait Loci (QTLs) affecting tumor incidence on chromosomes 3 and 5, latency on chromosomes 3, 9, 14, and 19, and multiplicity on chromosomes 13, 16, and 19. In addition, we unexpectedly identified a novel QTL on chromosome 6 controlling a lethal toxic phenotype in response to DMBA. Upon further investigation with chromosomes 6 and 13 congenic lines, in which an additional 114 rats were investigated, we mapped (1) a novel mammary tumor QTL to a region of 27.1 Mbp in the distal part of RNO6, a region that is entirely separated from the toxicity phenotype, and (2) a novel and powerful mammary tumor susceptibility locus of 4.5 Mbp that mapped to the proximal q-arm of RNO13. Comparison of genetic strain differences using existing rat genome databases enabled us to further construct priority lists containing single breast cancer candidate genes within the defined QTLs, serving as potential functional variants for future testing.

Genetic mapping of mammary tumor traits to rat chromosome 10 using a novel panel of consomic rats.

Identification of novel breast cancer susceptibility and resistance genes in genetically diverse human populations is challenging, and so inbred rats have been used to identify novel mammary cancer susceptibility quantitative trait loci (QTLs) with conventional mapping approaches. An alternative approach for QTL mapping is to use chromosome substitution (consomic) rat strains, which has the advantage of rapid generation of congenic from consomic animals. Using a novel rat strain pair, SS and BN, we identified rat mammary cancer QTLs in one of two consomic rat strains tested. Female rats of inbred parental (SS and BN) and two consomic (SS-10 BN and SS-12 BN) strains were treated with 7,12-dimethylbenz[a]anthracene orally. The phenotypes of tumor incidence, latency, and multiplicity were evaluated. SS rats were highly susceptible to mammary adenocarcinoma development, whereas BN rats were completely resistant. Statistical comparison of the phenotypes between the susceptible parental and the two consomic strains identified QTLs residing within chromosome 10 controlling mammary tumor latency and multiplicity. The study shows that SS-BN consomic rat strains can be used to map mammary tumor QTLs. This novel approach should accelerate positional cloning of mammary cancer susceptibility and resistant genes in the rat and the identification of homologous genes in humans.

Signet-ring cell carcinoma of the urinary bladder mimicking retroperitoneal fibrosis.

We present the case of a 77-year-old white woman with a past medical history of transitional cell carcinoma of the urinary bladder that presented with symptoms of acute renal failure and duodenal obstruction and posed a diagnostic dilemma. Initially, she presented with bilateral ureteral strictures and eventually required bilateral nephrostomy tubes. Later, the patient developed intractable nausea and vomiting secondary to a duodenal stricture. The finding of a "stranding appearance" on computed tomography imaging of the retroperitoneal space raised the suspicion of retroperitoneal fibrosis. Subsequent endoscopic placement of metal stents to relieve the duodenal obstruction failed to relieve her symptoms. The patient's poor general condition precluded an exploratory laparotomy. The patient expired shortly thereafter and an autopsy was performed. The autopsy results revealed full wall thickness signet-ring cell carcinoma of the urinary bladder with extensive metastasis to the retroperitoneum.

Mantle cell lymphoma of the hard palate: a case report and review of the differential diagnosis based on the histomorphology and immunophenotyping pattern.

To our knowledge, mantle cell lymphoma (MCL) has never been reported in the hard palate, but it is commonly observed in the nasopharynx and Waldeyer's tonsillar ring. MCL is characterized by a diffuse infiltrate of small lymphocytes with the expression of CD5, CD20, and cyclin D1 (Bcl-1), but not CD10. MCL presenting in the hard palate must be accurately distinguished from other forms of so-called small B-cell lymphomas-such as small lymphocytic lymphoma, follicular lymphoma, and extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue-because MCL possesses a worse prognosis. Awareness of MCL of the hard palate will prompt pathologists to perform adequate immunohistochemical analysis to aid in confirming the diagnosis.