Imaging and Management of Unusual Breast Neoplasms

Unusual breast neoplasms encompass a host of heterogeneous benign, borderline, and malignant entities, which often pose a management challenge when encountered on pathologic analysis after image-guided biopsy. Entities to be discussed in this article include select lesions of fibroepithelial, mesenchymal, and myoepithelial origin and nonneoplastic inflammatory lesions. Our objective is to discuss the imaging characteristics of these uncommon lesions and review management guidelines to facilitate radiologic-pathologic correlation and postbiopsy recommendations.

Imaging of Fibroepithelial Lesions: A Pictorial Essay

Stromal fibrosis in the breast is a non-specific benign pathologic entity with wide spectrum of imaging finding. The false-negative rates (number of cancers missed) previously reported have limited value because short follow-up period and small number of populations. To describe the mammographic and sonographic findings of stromal fibrosis of the breast diagnosed by imaging-guided biopsy and to determine the false-negative rate at percutaneous biopsy. Between January 2007 and December 2008, 3097 consecutive imaging-guided breast core biopsies were performed. Patients were included in our study if stromal fibrosis was the predominant pathologic finding. Patients who had received <2 years of follow-up were excluded. Mammographic and sonographic findings were reviewed. Follow-up imaging for >2 years and histologic data were reviewed to evaluate lesion stability. Stromal fibrosis was diagnosed in 187 (6.0%) of 3097 imaging-guided biopsies among patients with >2 years of follow-up (mean, 41.9 months). Among them, 91 (49%) of 187 lesions were not visible on mammography and calcifications were the most common findings, being identified in 33 lesions (17.6%). The most common sonographic finding was an oval hypoechoic mass with a circumscribed margin. Forty-two lesions (22.5%) were excised. Four false-negative lesions (2.1%, 4/187) were identified; all false-negative lesions were diagnosed within 6 months because of imaging-pathology discordance (75%, 3/4) or disease progression (25%, 1/4). Stromal fibrosis diagnosed by imaging-guided biopsy has a wide spectrum of imaging finding and can be managed safely with radiologic-pathologic correlation and subsequent short-term imaging follow-up.

It is unequivocally recognized that thyroid nodules are frequently detected in the adult population and mostly characterized by benign lesions (up to 70% of them), with only 5%–15% malignant lesions. The evaluation of thyroid lesions with fine-needle aspiration cytology (FNAC) represents one of the first and most useful diagnostic tools in the definition of their nature. Despite the fact that the majority of thyroid lesions are correctly diagnosed as either benign (70%–75%) or malignant (5%–10%) entities, the remaining nodules (20%–25%) represent the “gray zone” of follicular lesions, which belong to indeterminate categories, according to the different classification systems. This indeterminate group of lesions includes both benign and malignant entities, which cannot be easily discriminate with morphology alone. In these last decades, the increasing role of molecular testings, feasibly performed on cytological material combined with the discoveries of specific genetic alterations in the field of thyroid pathology, has opened the pace to their more accurate and specific contribution on cytology. In fact, in 2015, in the revised management guidelines for patients with thyroid nodules and well-differentiated thyroid cancers (WDTCs), the American Thyroid Association (ATA) confirmed the performance of molecular testing in thyroid indeterminate cytology, and the same performance was addressed in recent update of the management of thyroid nodules in the second edition of the Bethesda system for reporting thyroid cytopathology (TBSRTC). In the current review, we discuss the role of molecular tests for the different thyroid diagnostic categories of the Bethesda system for reporting thyroid cytopathology, mostly focusing our attention on the follicular and indeterminate lesions.

SummaryMesenchymal tumours represent a heterogenous group of neoplasms encopassing benign, intermediate malignancy, and malignant entities. Sarcomas account for approximately 1% of human malignancies. In consideration of their rarity as well as of intrinsic complexity, diagnostic accuracy represents a major challenge. Traditionally, mesenchymal tumours are regarded as lesions the occurrence of which is mostly limited to somatic soft tissues. However, the occurrence of soft tissue tumours at visceral sites represent a well recognized event, and the GI-tract ranks among the most frequently involved visceral location. There exist entities such as gastrointestinal stromal tumours (GIST) and malignant gastointestinal neuroectodermal tumors that exhibit exquisite tropism for the GI-tract. This review will focus also on other relevant clinico-pathologic entities in which occurrence at visceral location is not at all negligible.

Fibroblast-activation protein (FAP) is a key protein that is characteristically expressed by carcinoma-associated fibroblasts (CAFs). It has been shown to be expressed in CAFs of 90% of internal epithelial cancers as well as cutaneous epithelial malignancies. We have recently shown that this marker is useful in differentiating between morpheaform/infiltrative BCC from desmoplastic trichoepithelioma (TE). Given this, we sought to assess FAP expression in both benign and malignant cutaneous epithelial entities. Immunohistochemical FAP staining was performed on BCC (n=26), SCC (n=26), porocarcinoma (n=10), metastatic adenocarcinoma (n=12), keratoacanthoma (KA) (n=16), TE (n=14), pseudoepitheliomatous hyperplasia (n=15), poroma (n=15), syringoma (n=10), and chondroid syringoma (n=6). Control group consisted of scars (n=10). FAP expression was observed in all scars and all malignant entities, but not in any of the benign cases. Interestingly, ten KA cases exhibited positivity, whereas six were negative. In summary, FAP is a reliable marker of cutaneous epithelial malignancy.

Ovarian pathology ranges from innocuous non-neoplastic lesions to malignant neoplastic entities. The incidence, clinical appearance and the behaviour of the different types of ovarian tumour is extremely variable. In order to have a better understanding of frequency and histomorphological patterns of different ovarian lesions study was encountered in our tertiary care hospital.To study the histopathology of ovarian non-neoplastic and neoplastic lesions and to study the distribution of ovarian lesions with respect to various parameters like age, bilaterality, gross and microscopic features.This is a prospective study of 125 ovarian specimens received in department of pathology, G.K. General Hospital, Bhuj during August 1, 2018 to July 31, 2020. Total 125 cases of ovarian specimens were studied, amongst them 58 were non-neoplastic and remaining 67 were neoplastic. The most common non-neoplastic lesion seen was follicular cysts 12 cases (21%), followed by endometriosis 9 cases (16%). Among 67 neoplastic ovarian lesions 58(87%) cases were benign, 3(4%) cases were borderline and 6 (9%) cases were malignant. In benign ovarian neoplasm, most commonly seen lesions were serous cystadenoma 24 cases (36%) followed by 13 cases (20%) of mature cystic teratoma. In malignant cases, maximum was of high-grade serous cystadenocarcinoma.Ovarian epithelial tumours are the most common type, while serous cystadenocarcinoma was the most common malignancy. Histological examination is gold standard and in certain difficult cases require immunohistochemistry.Ovary is an important reproductive organ with involvement in production of progeny.Ovarian pathology ranges from innocuous non-neoplastic lesions to malignant neoplastic entities. Ovarian neoplasms have become increasingly important not only because of the wide range of neoplasms, but also because they have gradually increased the mortality rate. The incidence, clinical appearance and the behaviour of the different types of ovarian tumour is extremely variable.

SummaryRenal mesenchymal neoplasms are rare entities which can have a benign or a malignant behavior. Herein we describe two renal mesenchymal tumors with myxoid stroma, investigating the wide spectrum of differential diagnosis. With our first case we considered some benign entities such as myxoma, myxoid leiomyoma, and mixed epithelial and stromal tumor; with our second case we considered some sarcomas with myxoid features such as myxofibrosarcoma, low-grade fibromyxoid sarcoma, dedifferentiated liposarcoma, and myxoid liposarcoma. During the diagnostic process, it is important to integrate histopathological, immunohistochemical, and molecular data in order to avoid misdiagnosis. We concluded our second case report was a myxofibrosarcoma grade 1. To the best of our knowledge, we described the fourth primary renal myxofibrosarcoma reported in literature.

Basaloid salivary gland neoplasms (BSNs) are notoriously difficult to classify in fine needle aspiration (FNA) specimens due to the morphologic overlap of benign and malignant entities. Adenoid cystic carcinoma (AdCC) represents a particular diagnostic challenge, as it typically shows low-grade cytologic features despite its aggressive clinical behavior. We examined whether the proliferation markers Ki-67 and PHH3 could help predict malignancy in BSNs. A retrospective search was conducted to identify FNA cases of BSNs that had adequate tumor cellularity in the cell block and a subsequent excision specimen. Ki-67 and PHH3 immunohistochemical stains were performed. Aperio (Leica Biosystems) was used to calculate the percentage of tumor cell nuclear expression. Proliferation scores and final histopathologic diagnoses were correlated using a two-sided p-value test. Ten benign and 14 malignant basaloid neoplasms were analyzed. Benign cases showed low mean percentages of tumor cell staining for Ki-67 (1.14%) and PHH3 (0.84%), while malignant cases showed significantly higher mean percentages, especially with Ki-67 (19% for low-grade malignancies and 25.5% for high-grade malignancies). The difference in proliferation marker scores between the benign and low-grade malignant cases showed statistical significance for both Ki-67 (p = 0.0041) and PHH3 (p = 0.00397). The difference between benign entities and AdCC was also statistically significant for Ki-67 (p = 0.0013) and PHH3 (p = 0.002). Ki-67 and PHH3 analysis in cell block material may help predict malignancy in a cytologic specimen from a BSN, offering a valuable ancillary tool for cases with cytomorphologic ambiguity. In particular, the ability to suggest a sample is more likely to be AdCC rather than another morphologically similar low-grade BSN would be helpful for surgical planning.

Papillary lesions of the breast encompass a wide spectrum of benign and malignant entities. Cytological interpretation of these is difficult and they top the list of conditions with a risk of false-positive diagnosis. Understanding the correlation of histologically confirmed benign and malignant papillary neoplasm with demographic parameters and features of neoplasm will help to distinguish the different lesions. To compare histologically confirmed benign and malignant papillary neoplasm with demographic parameters and features of neoplasm A retrospective study was performed from January 2010 to December 2015 in the cytology section, Department of Pathology of a tertiary care and referral hospital including patients diagnosed as papillary lesion on FNAC. Histopathological follow-up was available for total 44 cases. A total of 44 breast aspirates and their corresponding histology were reviewed. Majority of the patients with benign and malignant neoplasm had age between 41-50 years (33%) and 51-60 years. All patients with benign neoplasm were women whereas among patients with malignant neoplasm 12 were women and one was a man. Benign papilloma, 36.3% cases showed cellular smear, followed by 27.2% showed moderate cellularity. Malignant papillary lesions, cases showed both cellular and moderate cellularity. Papillary carcinoma is an infrequent histologic subtype of breast carcinoma. Cytological diagnosis of the lesion is difficult due to overlap with benign entity and other mimics.

The classification of vascular tumors of the skeleton can be thought of as a spectrum of disease including both benign and malignant entities. Chapter 60 focuses on the benign entities, hemangioma and epithelioid hemangioma. The term hemangioma refers to a collection of blood vessels and vascular spaces, perhaps better classified as a slow-flow vascular malformation. Epithelioid hemangioma is a rare and controversial entity that may be confused with its malignant counterpart, the epithelioid hemangioendothelioma. This chapter will describe the clinical, pathophysiological, and imaging features of these benign vascular bone tumors, with a brief mention of treatment strategies. Familiarity with the imaging appearances and characteristics of these entities is essential in order to guide clinical management and to avoid unnecessary investigation into clearly benign lesions.

The presence of mammographically evident hyperdense foci within axillary lymph nodes elicits concern for calcium deposits, which in turn have a wide differential diagnosis including both benign and malignant entities. Tissue sampling, most commonly by way of image-guided core needle biopsy, is needed in many cases when a definite etiology cannot be clinically established. In this case series we present history, imaging findings, and pathology results (or long term follow-up stability as biopsy surrogate) of several women with body tattoos who at mammography were noted to have a characteristic pattern of "bubbly" pseudo-calcifications within axillary lymph nodes, and absence of other mammographic, sonographic and clinical abnormalities.

Pancreatic ductal adenocarcinoma is the most common malignant tumor of the pancreas. The remaining pancreatic tumors are a diverse group of pancreatic neoplasms that comprises cystic pancreatic neoplasms, endocrine tumors and other uncommon pancreatic tumors. Due to the excellent soft tissue contrast resolution, magnetic resonance imaging (MRI) is frequently able to readily separate cystic from noncystic tumors. Cystic tumors are often easy to diagnose with MRI; however, noncystic non-adenocarcinoma tumors may show a wide spectrum of imaging features, which can potentially mimic ductal adenocarcinoma. MRI is a reliable technique for the characterization of pancreatic lesions. The implementation of novel motion-resistant pulse sequences and respiratory gating techniques, as well as the recognized benefits of MR cholangiopancreatography, make MRI a very accurate examination for the evaluation of pancreatic masses. MRI has the distinctive ability of non-invasive assessment of the pancreatic ducts, pancreatic parenchyma, neighbouring soft tissues, and vascular network in one examination. MRI can identify different characteristics of various solid pancreatic lesions, potentially allowing the differentiation of adenocarcinoma from other benign and malignant entities. In this review we describe the MRI protocols and MRI characteristics of various solid pancreatic lesions. Recognition of these characteristics may establish the right diagnosis or at least narrow the differential diagnosis, thus avoiding unnecessary tests or procedures and permitting better management.

BACKGROUND The skin is the largest organ of the human body and plays a critical role in maintaining homeostasis. It helps regulate body temperature, protects against physical and chemical environmental insults, and serves as a barrier to microbial invasion by acting as a vital interface between the internal body and the external environment. Skin neoplasms encompass a wide variety of tumors. Because they are heterogeneous in their cell of origin, biological behavior, treatment, and prognosis, their classification is often complex and can sometimes mislead clinicians in distinguishing clearly between malignant and benign entities. CASE REPORT In this article, we report the case of a previously healthy man who presented with a solitary subcutaneous left leg skin nodule. After appropriate clinical examination, surgical excision, radiological tests, and pathological analysis, it was ultimately diagnosed as cribriform tumor (previously known as primary cutaneous cribriform carcinoma), an exceedingly rare adnexal skin neoplasm, which has been reported approximately only 50 times in the scientific literature. We describe its clinical features and biological characteristics, and describe the diagnostic procedure and available treatment. Because of the rarity of this tumor and consequently the limited research and available data, diagnosis and treatment can be particularly challenging for histopathologists and clinicians. CONCLUSIONS This article provides additional insights and description of this extremely rare entity, cribriform tumor, contributing to the growing body of evidence and aiding clinicians in avoiding potential misdiagnosis with other malignant or benign skin neoplasms.

Unusual tumors and tumor-like lesions are rare in the stomach and occur with variable incidence. Such lesions have either epithelial or mesenchymal origin, and present with non-specific clinical features like abdominal pain, melena, vomiting, and have overlapping radiological features, and thus, mimic other gastric tumors which may have markedly different management and prognosis. At times, esophagogastroduodenoscopy (EGD), different imaging modalities, and even histopathology of endoscopic biopsy may be non-contributory owing to atypical presentation, rare occurrence and unfamiliarity of radiologists or pathologists with such rare lesions. Even repeated endoscopic biopsies may prove inconclusive and in such situations excision of the lesion with confidence and its further histopathological examination helps us to reach a definitive diagnosis. Here, we present a heterogeneous collection of such gastric lesions mainly to emphasize the importance of a thorough and meticulous histopathological examination and the familiarity of a pathologist with these lesions during the evaluation of all gastric lesions, which in the light of relevant clinical information, EGD findings and radiological impression can lead to a prompt and correct diagnosis.