The aim of this review is to provide the surgical pathologist an overview of lobular lesions, from in situ to invasive carcinoma and the variants, by discussing the epidemiology, clinical characteristics, morphology, immunohistochemistry, known molecular data as well as the treatment recommendations. The recognition of histologic variants of both in situ and invasive lobular carcinoma has expanded the differential diagnosis. Awareness of these different entities is important as treatment recommendations continue to evolve.

Breast specimens are some of the more common specimens sent to the pathology laboratory for diagnosis. From a clinical perspective, the diagnoses fall into three broad categories: benign, atypical and malignant with patients then being managed according to established guidelines. However, the pathologic diagnosis can sometimes be challenging, and the distinction between these categories is sometimes far more subtle and subjective than non-pathologist may understand. One recurring diagnostic challenge in breast pathology is the diagnosis of atypical ductal hyperplasia (ADH) versus ductal carcinoma in situ (DCIS). While many cases are straightforward, others are quite borderline and challenging to classify consistently with significant interobserver variation amongst pathologists. The distinction between ADH and DCIS is critical from a clinical management perspective because one is treated as a risk factor, and the other as a malignancy that will be completely surgically excised and may require radiation therapy. This review will address the spectrum of ADH and DCIS with the associated diagnostic challenges in the real-world setting from presentation at core needle biopsy to surgery.

Targetoid hemosiderotic hemangioma (THH), also known as hobnail lymphatic malformation (HLL) or hobnail hemangioma, is an uncommon, acquired vascular lesion with a dynamic presentation and an unclear etiology. It predominantly affects adults with an age range from 9 to 78 years and has no gender predilection. The lesion is thought to arise from trauma, leading to micro-shunts between small lesional capillaries and adjacent lymphatic vessels.

Salivary gland-like tumors of the breast are rare neoplasms that share morphologic, immunophenotypic, and/or genetic features with their salivary gland counterparts, highlighting a shared underlying histopathogenesis in most cases. Salivary gland-like carcinomas included in the World Health Organization classification of breast tumors are adenoid cystic carcinoma, secretory carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and the exceedingly rare polymorphous adenocarcinoma. These carcinomas are usually triple negative for estrogen receptor and progesterone receptor expression and HER2 overexpression, yet generally have favorable prognosis, in contrast to high-grade triple negative carcinomas of no special type. On the other hand, a small subset, such as solid-basaloid adenoid cystic carcinoma, rare high-grade carcinomas, and those associated with transformation to other types of high-grade invasive carcinoma can behave more aggressively. Other salivary gland-like tumors of the breast, such as pleomorphic adenoma and adenomyoepithelioma, are usually benign but can rarely undergo malignant transformation. Although clinical experience with salivary gland-like breast tumors is overall limited, their recognition and accurate classification has important implications for prognosis and clinical management, especially to avoid overtreatment of salivary gland-like carcinomas. The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.

Achieving clear resection margins at the time of lumpectomy is essential for optimal patient outcomes. Margin status is traditionally determined by pathologic evaluation of the specimen and often is difficult or impossible for the surgeon to definitively know at the time of surgery, resulting in the need for re-operation to obtain clear surgical margins. Numerous techniques have been investigated to enhance the accuracy of intraoperative margin and are reviewed in this manuscript.

Ameloblastoma is a true benign odontogenic epithelial tumor, primarily arising in the jaw, and ranks as the second most prevalent odontogenic neoplasm following odontoma. Known for its diverse clinical, radiographic, and histological manifestations, ameloblastoma encompasses a wide spectrum of presentations. Unicystic ameloblastomas (UAs), a less common and generally less aggressive variant, appear as cystic lesions that can mimic ordinary jaw cysts in their clinical and radiologic features. However, histological examination reveals a distinctive odontogenic epithelium lining the cyst cavities, with some cases exhibiting luminal and mural growth. This article presents a unique case involving a 40-year-old female patient who experienced swelling in the right posterior maxilla for four months. Initially presumed to be a routine ameloblastoma, subsequent histopathological analysis identified it as an intraluminal type of UA with rare plexiform changes. It is characterized by a cystic space lined with ameloblast-like cells in a plexiform arrangement, setting it apart from other UA subtypes. Imaging often reveals a unilocular cystic appearance, which may obscure differential diagnosis by closely resembling other odontogenic cysts. The variations within ameloblastoma have always sparked considerable discussion, and we aim to elucidate the reasons behind this specific transformation and its distinctive characteristics.

Adenoid ameloblastoma (AA) is a rare benign but locally aggressive odontogenic tumor originating from the remnants of the dental lamina or enamel organ. It was newly incorporated into the 2022 WHO classification of odontogenic lesions, standing as the sole novel entity in this update. AA is also regarded as a hybrid tumor because of the combination of histological characteristics observed in both adenomatoid odontogenic tumors and ameloblastoma. Clinically, it presents similarly to other ameloblastoma variants, with patients typically exhibiting a painless, slow-growing jaw swelling. However, this subtype is noted for its more aggressive behavior, including a higher recurrence rate and greater local invasiveness. Histopathologically, AA is distinguished by an intricate arrangement of epithelial islands, cords, and strands, generating a cribriform architectural pattern, with peripheral palisading and central stellate reticulum-like formations. Immunohistochemical profiling reveals the expression of epithelial differentiation markers, including cytokeratins, and proliferative markers such as Ki-67, further corroborating its aggressive phenotype. While its precise etiopathogenesis remains obscure, the unique histological characteristics imply a potentially distinct underlying molecular pathway. Due to its aggressive nature, AA necessitates meticulous clinical and histopathological evaluation and tailored therapeutic strategies to mitigate recurrence risks and optimize patient prognoses. Furthermore, this review integrates histological and molecular insights from recent studies conducted after its inclusion in the updated WHO classification.

Several neoplastic and non-neoplastic proliferations of the appendix can show varying degrees of serrated epithelial architecture. Of these, diffuse mucosal hyperplasia is most common, followed in frequency by low-grade mucinous and serrated neoplasms. It is important to distinguish serrated appendiceal neoplasms from their potential mimics because these entities may be managed differently. Diffuse mucosal hyperplasia is a non-neoplastic change that usually develops in the setting of resolving appendicitis and requires no further therapy or surveillance, and serrated neoplasms confined to the mucosa are adequately treated by appendectomy alone. On the other hand, low-grade appendiceal mucinous neoplasms may require surveillance, and those with extra-appendiceal spread differ from adenocarcinomas arising from serrated neoplasms with respect to both treatment and prognosis. Low-grade mucinous neoplasms in the peritoneum are frequently amenable to peritoneum-directed therapies alone, while adenocarcinomas derived from serrated neoplasms often spread to both regional lymph nodes and the peritoneum, potentially requiring right colectomy and systemic chemotherapy. The purpose of this review is to summarize the literature regarding the clinical and pathologic features of appendiceal lesions that show epithelial serration and provide the reader with helpful tips to distinguish serrated neoplasms from their mimics.

Well-differentiated neuroendocrine tumors are the most common neoplasm of the appendix. They are graded and staged using World Health Organization and American Joint Committee on Cancer criteria, respectively. They may be invisible grossly or form rounded yellow nodules, sometimes in the appendiceal tip. They show classic neuroendocrine tumor features microscopically, forming nests and cords of monotonous cells with salt-and-pepper chromatin and amphophilic cytoplasm. They are positive for neuroendocrine markers by immunohistochemistry, but their molecular characteristics are not well defined. pT-category staging relies primarily on tumor size, though higher-stage cases may involve the subserosa or mesoappendix. Few entities enter the differential diagnosis, but lesions such as goblet cell adenocarcinoma, poorly differentiated neuroendocrine carcinoma, and mixed neuroendocrine-non-neuroendocrine neoplasm may be considered. Appendiceal neuroendocrine tumors may metastasize to regional lymph nodes, but farther spread is rare. The most consistently proven risk factor for such spread is tumor size, though different studies have proposed different cutoffs. Other potential risk factors include lymphovascular invasion and margin positivity. Tumors smaller than 1 cm can be treated by appendectomy, while hemicolectomy is recommended for tumors larger than 2 cm. Proper treatment for cases measuring 1-2 cm remains a matter of debate.

Appendix, considered a vestigial and disposable organ, has been long neglected as a source of abdominal tumors. Among the appendiceal tumors, goblet cell adenocarcinoma (GCA) is a rare primary epithelial neoplasm which has undergone multiple name changes and classifications in recent years, adding to confusion surrounding this unique amphicrine tumor. This entity was previously known as goblet cell carcinoid and adenocarcinoma ex goblet cell carcinoid. This review article provides an update on pathology, nomenclature, and recent classification systems with emphasis on 2019 World Health Organization Classification of Tumors, 3-tiered grading system..

Mucinous neoplasms of the appendix comprise a group of diagnostically challenging lesions that have generated significant controversy and confusion throughout the years, given their potential for aggressive behavior despite very bland cytologic features. Numerous classification schemes have been proposed to characterize and stage these lesions, but confusion remains among pathologists, surgeons, and oncologists regarding diagnostic criteria, therapeutic implications, and overall prognosis. This review summaries the current recommended nomenclature, histologic characteristics of each entity, and helpful features to distinguish neoplasia from benign mimics.

The calcifying odontogenic cyst (COC) is an uncommon developmental odontogenic cyst, the oral counterpart of Malherbe's cutaneous calcifying epithelioma (pilomatricoma). This article presents two unique cases of calcifying odontogenic cysts each exhibiting distinctive histopathological features and its literature review. One case with an unexpected finding of cholesterol granuloma (CG), a rare occurrence in non-inflammatory cysts within an unusual location between two maxillary central incisors. One more instance involves the presence of a compound odontome in conjunction with COC. The cases underscore the clinical and histopathological diversity of COC and highlight the importance of radiological and histopathological assessments for accurate diagnosis. The unexpected association of COC with cholesterol granuloma challenges traditional diagnostic expectations. Additionally, the second case suggests that COCs may warrant sub-categorization to better understand their varied presentations and biological behavior. This article contributes to the expanding knowledge of COC, emphasizing the significance of documenting rare cases to enhance comprehension of its nature, pathogenesis, and oral cavity origin.

For many years, odontogenic tumors have been known to present both clinical and histopathological challenges due to their origins in the epithelial, ectomesenchymal, and/or mesenchymal components of tooth-forming tissues. Gaining a comprehensive understanding of both common and rare odontogenic tumors is crucial for their effective study and clinical management. One particularly puzzling tumor is the "plexiform ameloblastoma," a variant of the solid multicystic ameloblastoma. This term describes a distinct pattern of epithelial proliferation within the cystic cavity. Numerous studies have emphasized the variability of the stromal component, further highlighting the enigmatic nature of ameloblastoma. The presence of unique and rare features, such as primitive, mature desmoplastic, hemangiomatous, or ghost cells within the stroma of plexiform ameloblastoma, underscores the differentiation potential of the neoplastic odontogenic epithelium and offers significant insights into the tissue reactions associated with this condition. This case review discusses four instances of plexiform ameloblastoma, illustrating various atypical stromal changes and their influence on patient prognosis. It also provides important criteria for analyzing stromal alterations related to this complex odontogenic tumor.

Sclerosing Odontogrenic Carcinoma (SOC) is a recent addition to the category of odontogenic tumours, which was first described by Koutlas et al. in 2008. It was described as primary intraosseous carcinoma with bland cytology, sclerotic stroma with presence of local infiltration showing aggressive behaviour. Following its discovery and the presentation of first case, only a handful of cases have been reported till date, which may be due to underreporting of the cases or inclusion of the case to other diagnosis since the features of this tumour overlaps with many other lesions of the oral cavity. Due to this factor, the pathogenesis of this category of tumours still remains enigmatic. The clinical features as a result of this factor are also not reported of the consistent type and overlaps with the already existing clinical features of other lesions. This lesion has only appeared till date twice in WHO classification of Odontogenic Cysts and Tumours. Thereby, the literature on this category is still in paucity. Therefore, the present review takes into account all of the features, diagnostic criteria and the markers discovered for this lesion and would provide an insight into whether this lesion is justified as a malignant lesion or should not be considered as a separate category of odontogenic tumour.

Odontogenic lesions are a category of lesions, which are found to be arising from the remnants of the tooth-bearing tissues of the body, that can be cystic in nature as a result of degeneration or as a result of excessive proliferation of these cells, can result in the formation of odontogenic tumours which are found in gnathic bones in the body. Since their discovery in literature and the explanation provided for their pathogenesis, these lesions have been the subject of debate and controversy amongst researchers as well as practitioners. Thereby, this review has taken into consideration one such odontogenic tumour, Calcifying Cystic Odontogenic Tumour (CCOT), which first were included under the namesake (Calcifying odontogenic cyst) as a sperate subheading under this cyst, but now has been designated under the category of tumours along with various histologic subtypes classified and described henceforth. Although the lesion has been removed in the recent classification, a wide variety of lesions in biphasic form has been reported in the past. Therefore, this present review takes a sneak-peek into this lesion with insight into its presentation, incidence, aetiology, pathogenesis, histopathology and all the controversies surrounding this category of lesion and the current literature about this lesion with proving the fact that this needs to be considered again in the category of odontogenic tumours.

Appendiceal adenocarcinoma (ApAC) is a rare malignancy, comprising less than 1 % of all gastrointestinal tumors. The current World Health Organization classifies ApAC as mucinous or nonmucinous. Mucinous ApAC are composed of pools of mucin lined by cells with low- and high-grade cytology and areas of infiltrative invasion. Nonmucinous ApAC histologically resemble conventional colorectal adenocarcinomas and have a worse prognosis than their mucinous counterpart. Unfortunately, the nomenclature and histologic classification of ApAC, specifically the mucinous subtype, has changed several times throughout the years, contributing to diagnostic confusion for pathologists. The treatment for mucinous ApAC differs from that of other appendiceal mucinous neoplasms, thus accurate diagnosis is key to patient management and outcome. This review discusses the current classification and staging of ApAC with a particular emphasis on the mucinous subtype and peritoneal disease, as these areas are the most challenging for practicing surgical pathologists.

The Calcifying Odontogenic Cysts (COC) displays a wide range of clinical and histopathological variations as well as diverse biological behaviors. This diversity has led to confusion and disagreement regarding the terminology and classification of this lesion. The previous classification attempts to categorize COC into two concepts. The first concept, termed "monistic," suggests that all COCs are neoplastic despite the majority being cystic in structure and seemingly non-neoplastic. The second concept, known as "dualistic," posits that COC comprises two distinct entities: a cyst and a neoplasm. This research discusses various previous classifications of COC found in the literature and proposes a new, straightforward universal classification based solely on histopathology, aiming to facilitate understanding for surgeons.