Case of recurrent superficial CD34-positive fibroblastic tumor.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare superficial mesenchymal tumor. SCPFT has a distinctive morphologic appearance, marked by significant nuclear pleomorphism, low mitotic rate, and diffuse CD34 positivity. SCPFT is underdiagnosed because of its rarity and misdiagnosis as sarcoma, with very few reported cases of local recurrence or metastasis. Recognition and awareness of SCPFT are essential for accurate diagnosis and appropriate clinical management. We describe here the case of a 37-year-old male who presented with a right calf mass diagnosed as SCPFT with subsequent local recurrence of the tumor.

The Recent Advances in Molecular Diagnosis of Soft Tissue Tumors.

Soft tissue tumors are rare mesenchymal tumors with divergent differentiation. The diagnosis of soft tissue tumors is challenging for pathologists owing to the diversity of tumor types and histological overlap among the tumor entities. Present-day understanding of the molecular pathogenesis of soft tissue tumors has rapidly increased with the development of molecular genetic techniques (e.g., next-generation sequencing). Additionally, immunohistochemical markers that serve as surrogate markers for recurrent translocations in soft tissue tumors have been developed. This review aims to provide an update on recently described molecular findings and relevant novel immunohistochemical markers in selected soft tissue tumors.

Mediastinal neuroblastoma, ganglioneuroblastoma, and ganglioneuroma: Pathology review and diagnostic approach.

Neuroblastic tumors are a group of tumors of the sympathetic ganglia and adrenal medulla that derive from primordial neural crest cells. These tumors include neuroblastoma, intermixed ganglioneuroblastoma, nodular ganglioneuroblastoma, and ganglioneuroma. Neuroblastomas are the most common extracranial solid tumor arising in childhood and may occur in different anatomic sites. Neuroblastic tumors are common mesenchymal tumors of the mediastinum. Herein, we describe advances in our understanding of neuroblastic tumor biology. Pathologists should be aware of diagnostic challenges associated with these tumors to ensure correct histologic diagnosis and appropriate clinical management. We describe updated mediastinal neuroblastic tumor pathology, focusing on morphological, immunohistochemical, and molecular features and differential diagnoses.

Superficial CD34-positive fibroblastic tumor (SCPFT): A review of pathological and clinical features.

Superficial CD34-positive fibroblastic tumor (SCPFT) is a recently described rare mesenchymal tumor of borderline malignancy. It generally involves superficial soft tissue, with a predilection to the lower extremities. Microscopically this tumor is characterized by a fascicular and storiform growth pattern, spindled to epithelioid cells, nuclear atypia with pleomorphism, and eosinophilic granular, and fibrillar to glassy cytoplasm. Strong diffuse immunoreactivity for CD34 is very characteristic of this entity. Due to under-recognition, this tumor is generally underreported. Additionally, cases of recurrence are rarely reported in the literature. We will comprehensively review the English language literature on all reported cases of SCPFT, with emphasis on recurrence.

Mesenchymal Tumors of the Mediastinum: An Update on Diagnostic Approach.

Mesenchymal tumors of the mediastinum are a heterogenous group of rare tumors with divergent lineages. Mediastinal mesenchymal tumors are diagnostically challenging due to their diversity and morphologic overlap with nonmesenchymal lesions arising in the mediastinum. Accurate histologic diagnosis is critical for appropriate patient management and prognostication. Many mediastinal mesenchymal tumors affect distinct age groups or occur at specific mediastinal compartments. Neurogenic tumors, liposarcoma, solitary fibrous tumor, and synovial sarcoma are common mesenchymal tumors in the mediastinum. Herein, we provide an update on the diagnostic approach to mediastinal mesenchymal tumors and a review of the histologic features and differential diagnosis of common benign and malignant mesenchymal tumors of the mediastinum.

Mediastinal Germ Cell Tumors: A Review and Update on Pathologic, Clinical, and Molecular Features.

Mediastinal germ cell tumors (MGCTs) are the most common extragonadal germ cell tumors (GCTs) and most often arise in the anterior mediastinum with a male predilection. MGCTs also have a predilection for patients with Klinefelter syndrome and possibly other genetic conditions. MGCTs, as GCTs at other extragonadal sites, are thought to arise from germ cells improperly retained during migration along the midline during embryogenesis. Similar to their counterparts in the testes, MGCTs are classified into seminomatous and nonseminomatous GCTs. Seminomatous MGCT represents pure seminoma, whereas nonseminomatous MGCTs encompass pure yolk sac tumors, embryonal carcinoma, choriocarcinoma, mature or immature teratoma, and mixed GCTs with any combination of GCT types, including seminoma. Somatic-type or hematologic malignancies can also occur in association with a primary MGCT. MGCTs share molecular findings with GCTs at other sites, most commonly the presence of chromosome 12p gains and isochromosome i(12p). Treatment includes neoadjuvant chemotherapy followed by surgical resection of residual tumor, with the exception of benign teratomas, which require only surgical resection without chemotherapy. In this review, we highlight and provide an update on pathologic, clinical, and molecular features of MGCTs. Immunohistochemical profiles of each tumor type, as well as differential diagnostic considerations, are discussed.

The 2020 WHO Classification of Tumors of Bone: An Updated Review.

Bone tumors are a rare and heterogeneous group of neoplasms that occur in the bone. The diversity and considerable morphologic overlap of bone tumors with other mesenchymal and nonmesenchymal bone lesions can complicate diagnosis. Accurate histologic diagnosis is crucial for appropriate management and prognostication. Since the publication of the fourth edition of the World Health Organization (WHO) classification of tumors of soft tissue and bone in 2013, significant advances have been made in our understanding of bone tumor molecular biology, classification, prognostication, and treatment. Detection of tumor-specific molecular alterations can facilitate the accurate diagnosis of histologically challenging cases. The fifth edition of the 2020 WHO classification of tumors of soft tissue and bone tumors provides an updated classification scheme and essential diagnostic criteria for bone tumors. Herein, we summarize these updates, focusing on major changes in each category of bone tumor, the newly described tumor entities and subtypes of existing tumor types, and newly described molecular and genetic data.

The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes and New Entities.

Soft tissue tumors are a relatively rare and diagnostically challenging group of neoplasms that can have varying lines of differentiation. Accurate diagnosis is important for appropriate treatment and prognostication. In the 8 years since the publication of the 4th Edition of World Health Organization (WHO) classification of soft tissue tumors, significant advances have been made in our understanding of soft tissue tumor molecular biology and diagnostic criteria. The 5th Edition of the 2020 WHO classification of tumors of soft tissue and bone incorporated these changes. Classification of tumors, in general, but particularly in soft tissue tumors, is increasingly based on the molecular characteristics of tumor types. Understanding tumor molecular genetics improves diagnostic accuracy for tumors that have been difficult to classify on the basis of morphology alone, or that have overlapping morphologic features. In many large hospitals in the United States and Europe, molecular tests on soft tissue tumors are a routine part of diagnosis. Therefore, surgical pathologists should be familiar with newly emerging molecular genetic techniques in clinical settings. In the near future, molecular tests, particularly in soft tissue tumor diagnosis, will become as routine during diagnosis as immunohistochemistry is currently. This new edition provides an updated classification scheme and essential diagnostic criteria for soft tissue tumors. Newly recognized entities and subtypes of existing tumor types, several reclassified tumors, and newly defined molecular and genetic data have been incorporated. Herein, we summarize the updates in the WHO 5th Edition, focusing on major changes in each category of soft tissue tumor, and the newly described tumor entities and subtypes.

Leiomyoma of digit of hand: Report of three cases with literature review.

Leiomyoma is a benign tumor of smooth muscle origin most common in areas of the body with abundant smooth muscle including the gynecologic, genitourinary, and gastrointestinal system. Leiomyoma outside of these locations is believed to arise from vascular smooth muscle and arrector pili muscles. Leiomyoma of an extremity is a rare diagnosis, especially when present in a digit of the hand due to the paucity of smooth muscle in this location. We report three cases of leiomyoma of a digit of the hand.

Pleomorphic giant cell carcinoma of prostate: Rare tumor with unique clinicopathological, immunohistochemical, and molecular features.

Pleomorphic giant cell carcinoma (PGCC) of the prostate is a rare entity categorized as a variant of prostatic acinar adenocarcinoma in the 2016 World Health Organization (WHO) classification system. PGCC differs from conventional prostatic adenocarcinoma by having bizarre, markedly enlarged, and pleomorphic cells. It differs from high grade urothelial carcinoma by negativity for urothelial differentiation markers, and can be distinguished from sarcomatoid carcinoma by lack of spindle cells. Including two new cases described herein, there have been 51 cases of prostate PGCC reported in the English literature. Clinical features shared by cases of prostate PGCC include poor prognosis, occurrence in older patients, and frequent association with prior therapy. Pathologic features common to cases of prostate PGCC include admixture with a high-grade conventional prostate carcinoma component and absent or reduced expression of prostate differentiation markers. More recent studies have begun to elucidate the molecular characteristics of PGCC, detecting specific mutations and chromosomal translocations, and showing evidence of a high degree of molecular instability in these tumors. We report novel findings in two cases of PGCC including a PIK3CA p.His1047Arg mutation not previously described. One of our cases is the first to clearly demonstrate chronological loss of prostate markers during dedifferentiation from prior conventional prostate carcinoma to PGCC. Herein, we present our two new cases and comprehensively review the literature on all reported cases of PGCC with critical commentary on findings in cases of this rare tumor.

Cribriform prostate cancer: Morphologic criteria enabling a diagnosis, based on survey of experts.

Among four sub-patterns of Gleason grade 4 prostate cancer, voluminous evidence supports that the cribriform pattern holds an unfavorable prognostic impact, as compared with poorly-formed, fused, or glomeruloid. The International Society of Urological Pathology (ISUP) recommends specifying whether invasive grade 4 cancer is cribriform. Recently, ISUP experts published a consensus definition of cribriform pattern highlighting criteria that distinguish it from mimickers. The current study aimed to analyze morphologic features separately to identify those that define the essence of the cribriform pattern. Thirty-two selected photomicrographs were classified by 12 urologic pathologists as: definitely cribriform cancer, probably cribriform, unsure, probably not cribriform, or definitely not cribriform. Consensus was defined as 9/12 agree or disagree, with ≤1 strongly supporting the opposite choice. Final consensus was achieved in 21 of 32 cases. Generalized estimating equation (GEE) model with logit link was fitted to estimate effect of multiple morphologic predictors. Fisher exact test was used for categorical findings. Presence of intervening stroma precluded calling cribriform cancer (p = 0.006). Mucin presence detracted (p = 0.003) from willingness to call cribriform cancer (only 3 cases had mucin). Lumen number was associated with cribriform consensus (p = 0.0006), and all consensus cases had ≥9 lumens. Predominant papillary pattern or an irregular outer boundary detracted (p = NS). Invasive cribriform carcinoma should have absence of intervening stroma, and usually neither papillary pattern, irregular outer boundary, nor very few lumens. Setting the criteria for cribriform will help prevent over- or undercalling this important finding.

Plasmacytoid Variant Urothelial Carcinoma of the Bladder: A Systematic Review and Meta-Analysis of Clinicopathological Features and Survival Outcomes.

PURPOSE: The clinicopathological features and treatment outcomes of plasmacytoid variant-urothelial carcinoma of the bladder have not been fully understood. We evaluated the clinicopathological characteristics and survival outcomes of plasmacytoid variant-urothelial carcinoma of the bladder compared to conventional urothelial carcinoma of the bladder. MATERIALS AND METHODS: A systematic review was performed following the PRISMA guideline. PubMed®/MEDLINE®, Embase® and Cochrane Library were searched up to June 2019. The differences in the clinicopathological features (stage pT3 or greater, lymph node metastasis, ureteral margin positive and perivesical soft tissue margin positive status) and survival outcomes (overall mortality and cancer specific mortality) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder were compared. The GRADE approach was used for rating the certainty of evidence. RESULTS: Eight studies were included. Patients with plasmacytoid variant-urothelial carcinoma of the bladder had a higher frequency of stage pT3 or greater (OR 3.84, 95% CI 1.63-9.03, p=0.002) and risk of lymph node metastasis (OR 2.58, 95% CI 1.15-5.76, p=0.02), ureteral margin positive (OR 12.18, 95% CI 4.62-32.13, p <0.00001) and perivesical soft tissue margin positive (OR 12.31, 95% CI 5.15-29.41, p <0.00001) status after radical cystectomy than those with conventional urothelial carcinoma of the bladder. Although there was no difference in cancer specific mortality (HR 1.40, 95% CI 0.82-2.40, p=0.22) between plasmacytoid variant-urothelial carcinoma of the bladder and conventional urothelial carcinoma of the bladder, plasmacytoid variant-urothelial carcinoma of the bladder had worse survival outcomes (overall mortality) than conventional urothelial carcinoma of the bladder approaching the borderline of significance (HR 1.62, 95% CI 0.98-2.68, p=0.06) when adjusted for other clinicopathological characteristics. CONCLUSIONS: Plasmacytoid variant-urothelial carcinoma of the bladder was strongly associated with adverse clinicopathological features and worse overall mortality compared to conventional urothelial carcinoma of the bladder after adjusting for other clinicopathological parameters, and plasmacytoid variant histology of urothelial carcinoma of the bladder is an independent prognostic factor for overall survival.

Lesions of anogenital mammary-like glands: Four cases including novel pathologic and immunohistochemical observations.

Anogenital mammary-like glands, formerly described as ectopic breast tissue, are currently considered to be normal histologic components of the anogenital region. Anogenital mammary-like glands can give rise to many lesions identical to counterparts in the native female breast. We describe four cases of such lesions, including fibroadenoma, gynecomastia-like hyperplasia, and ectopic mammary-type tissue with a spectrum of usual ductal hyperplasia, apocrine metaplasia, adenosis, and pseudolactational change. All four cases occurred in young women (ages 29-38) who presented with vulvar or perianal masses. Similar to previously reported cases, these lesions shared histologic and immunohistochemical characteristics identical to native female breast lesions. Novel findings in our cases included (1) the first case of gynecomastia-like change to be reported in the perianal area of a female, (2) Immunohistochemical staining identifying a 3-layered epithelium characterized by a population of CK14 and CK5/6 positive and hormone receptor negative superficial luminal cells, and (3) diffuse, strong positivity for GATA3 in all cases. Our study adds to the literature on these rare lesions and highlights findings which may be useful in understanding the pathogenesis and improving the diagnosis of anogenital mammary-like gland lesions.

Clinicopathologic study of 60 cases of urothelial neoplasms with inverted growth patterns: Reclassification by international consultation on urologic disease (ICUD) recommendations.

BACKGROUND: Most urothelial neoplasms of the bladder show an exophytic papillary pattern, but some show an inverted growth pattern. In 2004, the World Health Organization (WHO) released a detailed histologic classification system for papillary urothelial neoplasms, but not for inverted forms. The International Consultation on Urologic Disease (ICUD) recommendations of 2012 are applicable to inverted/endophytic papillary lesions as follows: 1) inverted papilloma (IP), 2) inverted papillary urothelial neoplasm of low malignant potential (IPUNLMP), 3) inverted papillary urothelial carcinoma, low grade, non-invasive (IPUCLG-NI), 4) inverted papillary urothelial carcinoma, high grade, non-invasive (IPUCHG-NI), 5) inverted papillary urothelial carcinoma, high grade, invasive (IPUCHG-I). However, only atypical cellular morphology was considered for classification in the 2012 ICUD recommendations, and data to support to validate this new grading system are lacking. METHODS: Sixty cases of inverted urothelial papillary tumors were classified into 5 categories according to 2012 ICUD and 2016 WHO/ISUP recommendations to evaluate their clinical, pathological, and immunohistochemical characteristics. Two subgroups were defined as subgroup 1, IP and IPUNLMP, and subgroup 2, IPUCLG-NI, IPUCHG-NI, and IPUCHG-I. Clinical features (age, sex, history of urothelial carcinoma, smoking history, size, and multifocality) and histologic features (nuclear pleomorphism, mitotic count, mitosis level, apoptosis, luminal necrosis, trabecular thickening, anastomosing trabeculae, hypercellularity, loss of polarity, peripheral palisading, palisading with central streaming, and discohesiveness) were evaluated. Immunohistochemical stains for CK20, CD44, P53, p16, Ki-67, cyclin D1 and c-erbB2 were performed. RESULTS: A total of 60 cases were classified as 10 cases of IP, 29 cases of IPUNLMPs, 15 cases of IPUCLG-NI, 4 cases of IPUCHG-NI, and 2 cases of IPUCHG-I. Compared to subgroup 1, subgroup 2 showed larger tumor size, more nuclear irregularity, higher mitotic count (hot spot and per 10 high power fields), more upper level mitosis (>1/2), and more frequent apoptosis, luminal necrosis, surface papillary component, trabecular thickening, anastomosing irregular trabeculae, hypercellularity, loss of polarity, peripheral palisading with central streaming, and discohesiveness, and absence of umbrella cells and urothelial eddies. CK20, Ki67, and c-erbB2 were the only markers that were differently expressed in the two subgroups, with more expression in subgroup 2. CONCLUSIONS: The 2012 ICUD recommendations are valid to classify inverted papillary urothelial tumors. However, other histologic features besides atypical cellular morphology should also be considered to distinguish subgroup 1 and subgroup 2 inverted papillary urothelial tumors.

Seminal vesicle invasion combined with extraprostatic extension is associated with higher frequency of biochemical recurrence and lymph node metastasis than seminal vesicle invasion alone: Proposal for further pT3 prostate cancer subclassification.

The 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system subdivides prostatic pT3 tumors into pT3a, which includes cases with extraprostatic extension (EPE) and pT3b, which is defined by the presence of seminal vesicle invasion (SVI) with or without EPE. Yet, it is not established whether combined SVI and EPE impart a worse prognosis compared to SVI alone. We studied a cohort of 69 prostatectomy patients with SVI with or without EPE. Patient age at the time of radical prostatectomy was documented and Gleason score and presence or absence of EPE and/or SVI were determined. Biochemical recurrence (BCR) was defined as a PSA rise >0.2 ng/mL. The frequency of BCR was 33.9% in cases with combined EPE and SVI versus 12.5% in cases with SVI alone (relative risk = 2.71). An additional cohort of 88 patients also showed a higher frequency of lymph node metastasis of 29% in patients with combined SVI and EPE at the time of radical prostatectomy versus a 10% frequency of lymph node metastasis in patients with SVI alone (relative risk = 2.9). Based on our data, we propose further subdividing pT3 prostate cancers into three groups: EPE alone (pT3a), SVI alone (pT3b), and combined EPE and SVI (pT3c). This classification system would more accurately identify patients with pT3 prostate cancer who are more likely to experience worse outcomes and provide clinicians with additional information to aid in follow-up and postoperative treatment decisions.

Neuroendocrine tumors of genitourinary tract: Recent advances.

Primary neuroendocrine tumors of the genitourinary tract are rare and are comprised of a heterogeneous group of neoplasms. These include paraganglioma, well-differentiated neuroendocrine tumors or carcinoid tumors, small-cell neuroendocrine carcinoma, and large-cell neuroendocrine carcinoma. Personal experiences, in addition to the findings of an extensive literature search for pertinent publications, were used to compile the epidemiological data, clinical information, histopathological features, prognostic factors, and therapeutic approaches. We also include molecular alterations and targeted treatments of the various neuroendocrine tumors of the genitourinary tract.

Dedifferentiated gastrointestinal stromal tumor: Recent advances.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal lesions of the gastrointestinal tract. A small minority of GISTs exhibit morphologic and phenotypic changes and differentiate into an unusual phenotype through the process of dedifferentiation. Dedifferentiation can occur either de novo or after prolonged treatment with imatinib, a selective tyrosine kinase inhibitor. GISTs can present with various morphologies including rhabdomyosarcoma, angiosarcoma, or undifferentiated pleomorphic sarcoma. The unusual histologic and immunohistochemical characteristics of these tumors can be diagnostically challenging. Therefore, it is essential that the pathologists recognize GISTs with unusual morphology and be aware of the dedifferentiation process. This review aims to provide an overview of the morphologic and molecular features of dedifferentiated GISTs. Additionally, we discuss diagnostic dilemmas and recent immunohistochemical markers that are useful in distinguishing dedifferentiated GISTs from other gastrointestinal tumors.

Clear cell carcinoma of testis: A review.

Clear cell Mullerian-type adenocarcinoma of the testis is an exceedingly rare entity, and its histogenesis and clinical behavior are still poorly understood. We discuss three cases of clear cell carcinoma of the testis, compiled from a review of the literature and our personal experience. Microscopically, the tumors closely resembled clear cell carcinoma of the ovary, displaying papillae lined by clear cells with areas of hobnailing. The reported immunophenotypic features were also similar to that of ovarian tumors, as positivity for epithelial markers (CK7, CAM5.2, AE1/AE3, EMA) and Mullerian markers (PAX8, CA125) with negativity for estrogen and progesterone receptors have been observed. The pathogenesis of testicular clear cell carcinoma is still poorly understood, with reported cases displaying evidence of both mesothelial and Mullerian origin. In addition, molecular characterization of testicular clear cell carcinomas has yet to be accomplished; however, studies performed on ovarian clear cell carcinomas may provide insight to the origin, biologic behavior, and potential therapeutic modalities for this obscure, aggressive malignancy.

Micropapillary adenocarcinoma of lung: Morphological criteria and diagnostic reproducibility among pulmonary pathologists.

CONTEXT: Invasive micropapillary adenocarcinoma (MPC) is an aggressive variant of lung adenocarcinoma, frequently manifesting with advanced stage lymph node metastasis and decreased survival. OBJECTIVE: Identification of this morphology is important, as it is strongly correlated with poor prognosis regardless of the amount of MPC component. To date, no study has investigated the morphological criteria used to objectively diagnose it. DESIGN: Herein, we selected 30 cases of potential MPC of lung, and distributed 2 digital images per case among 15 pulmonary pathology experts. Reviewers were requested to diagnostically interpret, assign the percentage of MPC component, and record the morphological features they identified. The noted features included: columnar cells, elongated slender cell nests, extensive stromal retraction, lumen formation with internal epithelial tufting, epithelial signet ring-like forms, intracytoplasmic vacuolization, multiple nests in the same alveolar space, back-to-back lacunar spaces, epithelial nest anastomosis, marked pleomorphism, peripherally oriented nuclei, randomly distributed nuclei, small/medium/large tumor nest size, fibrovascular cores, and spread through air-spaces (STAS). RESULTS: Cluster analysis revealed three subgroups with the following diagnoses: "MPC", "combined papillary and MPC", and "others". The subgroups correlated with the reported median percentage of MPC. Intracytoplasmic vacuolization, epithelial nest anastomosis/confluence, multiple nests in the same alveolar space, and small/medium tumor nest size were the most common criteria identified in the cases diagnosed as MPC. Peripherally oriented nuclei and epithelial signet ring-like forms were frequently identified in both the "MPC" and "combined papillary and MPC" groups. CONCLUSIONS: Our study provides objective diagnostic criteria to diagnose MPC of lung.

Flat epithelial atypia in directional vacuum-assisted biopsy of breast microcalcifications: surgical excision may not be necessary.

The aim of this study was to analyze the clinicopathological features of patients with flat epithelial atypia, diagnosed in directional vacuum-assisted biopsy targeting microcalcifications, to identify upgrade rate to in situ ductal or invasive breast carcinoma, and determine factors predicting carcinoma in the subsequent excision. We retrospectively evaluated the histological, clinical, and mammographic features of 69 cases from 65 women, with directional vacuum-assisted biopsy-diagnosed flat epithelial atypia with or without atypical ductal hyperplasia or atypical lobular hyperplasia, which underwent subsequent surgical excision. The extent and percentage of microcalcifications sampled by directional vacuum-assisted biopsy were evaluated by mammography. All biopsy and surgical excision slides were reviewed. The age of the women ranged from 40 to 85 years (mean 57 years). All patients presented with mammographically detected microcalcifications only, except in one case that had associated architectural distortion. Extent of calcifications ranged from <1 cm (n = 47), 1-3 cm (n = 15) to > 3 cm (n = 6), and no measurement (n = 1). A mean of 11 cores (range 6-25) was obtained from each lesion. Post-biopsy mammogram revealed >90% removal of calcifications in 81% of cases. Pure flat epithelial atypia represented nearly two-thirds of directional vacuum-assisted biopsy specimens (n = 43, 62%), while flat epithelial atypia coexisted with atypical ductal hyperplasia (18 cases, 26%), or atypical lobular hyperplasia (8 cases, 12%). Upon excision, none of the cases were upgraded to in situ ductal or invasive breast cancer. In one case, however, an incidental, tubular carcinoma (4 mm) was found away from biopsy site. Excluding this case, the upgrade rate was 0%. Our study adds to the growing evidence that diagnosis of flat epithelial atypia on directional vacuum-assisted biopsy for microcalcifications as the only imaging finding is not associated with a significant upgrade to carcinoma on excision, and therefore, excision may not be necessary. Additionally, excision may not be necessary for flat epithelial atypia with atypical ductal hyperplasia limited to ≤2 terminal duct-lobular units, if at least 90% of calcifications have been removed on biopsy.