Uncommon Tumor Research Articles

Dermatofibrosarcoma of Darrier and Ferrand: Recurrency Character: A Case-Report (Experience of the University Hospital Tangier-Tetouan-Al Hoceima)

Introduction: Dermatofibrosarcoma of Darier and Ferrand (DFSP) is a rare skin tumor characterized by its local aggressiveness and high potential. Its prognosis depends essentially on the quality of its management. Observation and Results: In this article, we report the case of a young patient treated at the Department of Plastic, Reconstructive and Aesthetic Surgery, Tangier, for a Darier and Ferrand dermatofibrosarcoma that recurred five times after surgical excision, with a 5-cm margin on the surface and a healthy anatomical barrier at depth. Coverage of the loss of substance (LOS) was performed after anatomopathological confirmation of the carcinological nature of the excision, and essentially involved skin grafting. Despite a course of radiotherapy prescribed at the 4th recurrence, a 5th rapid recurrence was noted. Discussion: The great clinical, histological and evolutionary polymorphism of this type of sarcoma results in an underestimated incidence and explains the delay in diagnosis. Recurrences are frequent, and usually local. Initial wide surgical excision is the reference treatment, and directly conditions the prognosis of DFSP. According to several studies, recurrence may depend on the quality of surgical excision, but could also be attributed to genetic or environmental factors, or to variations in the histological subtype of the sarcoma. Conclusion: Darier Ferrand is an uncommon tumor with local malignancy, whose evolutionary risk depends mainly on the quality of the initial excision. The chances of cure in the case of well performed primary surgery are significantly higher than in the case of salvage surgery. Tumor excision must the refore be wide and deep, with sacrifice of a healthy barrier at depth.

Ewing Sarcoma of the Female Genital Tract: Clinicopathologic Analysis of 21 Cases With an Emphasis on the Differential Diagnosis of Gynecologic Round Cell, Spindle, and Epithelioid Neoplasms.

Ewing sarcoma is an uncommon neoplasm considered in the differential diagnosis of tumors with "small round cell" morphology, but its occurrence in the gynecologic tract has only been sporadically documented. Herein, we describe the largest cohort of Ewing sarcoma localized to the female genital tract to date, and emphasize their clinicopathologic resemblance to more common gynecologic neoplasms. Ewing sarcoma (n=21) was retrospectively identified from 5 institutions. The average patient age was 35 (range 6-61) years. Tumor sites included uterus (n=8), cervix (n=4), vulva (n=5), vagina (n=1), broad ligament (n=1), inguinal area (n=1), and pelvis (n=1). Nine of 18 cases in which slides were available for review demonstrated only classic round cell morphology, with the remainder showing a variable combination and prominence of variant ovoid/spindle or epithelioid appearance. Tumors showed diffuse membranous reactivity for CD99 (20/20) and were positive for NKX2.2 (8/8, diffuse) and cyclin D1 (7/7, of which 3/7 were patchy/multifocal and 4/7 were diffuse). They were negative for ER (0/6) and CD10 (0/6). Three cases were initially diagnosed as endometrial stromal sarcomas. EWSR1 rearrangement was confirmed in 20/21 by fluorescence in situ hybridization (n=15) and/or sequencing (n=8). Of the eight tumors that underwent sequencing, 6 harbored FLI1, 1 ERG, and 1 FEV as the fusion partner. Of 11 patients with available follow-up, 5 died of disease, 1 developed lung metastases and 5 are alive with no evidence of disease. Ewing sarcoma of the gynecologic tract is a rare, aggressive entity that shares some morphologic and immunohistochemical features with other more common gynecologic neoplasms. In addition to the typical round cell appearance, variant spindled/ovoid to epithelioid morphology may also be observed and should prompt consideration of this entity with appropriate immunohistochemical and/or molecular studies.

A case of hyalinizing trabecular tumor of the thyroid: diagnostic significance of PAX8-GLIS3 fusion

BackgroundHyalinizing trabecular tumor (HTT) is an uncommon follicular cell-derived thyroid tumor classified as a low-risk neoplasm by the World Health Organization Classification of Tumors of Endocrine Organs, 5th edition. The PAX8-GLIS3 gene fusion is reportedly a pathognomonic genetic alteration of HTT.Case presentationA 43-year-old Japanese female was incidentally discovered to have an 8-mm, well-defined, hypoechoic mass in the left lobe of the thyroid gland by ultrasound examination. Contrast-enhanced computed tomography scan revealed a solid mass exhibiting slight homogeneous enhancement in the lower pole of the thyroid gland. The mass was diagnosed as atypia of undetermined significance by fine-needle aspiration cytology. The patient underwent left hemithyroidectomy with routine central compartment dissection. Histologic findings revealed tumor cells with elongated nuclei and intranuclear pseudoinclusions arranged with trabeculae architecture or small nests in hyalinized stroma. Weak membranous and cytoplasmic staining was found by MIB1 (Ki-67) immunostaining. The final diagnosis was HTT of the thyroid gland. Next-generation sequencing genetic analysis of a surgical specimen revealed no pathologic mutations, including BRAF, H/K/NRAS, or RET-PTC fusions. The PAX8-GLIS3 fusion was detected by RT-PCR.ConclusionsA rare case of HTT was demonstrated through imaging, cytologic, histologic and molecular investigations. PAX8-GLIS3 fusion detected by RT-PCR and Sanger sequencing was confirmed to be a genetic hallmark of HTT.

Mature cystic teratoma with co-existent mucinous cystadenocarcinoma: describing a diagnostic challenge—a case report

BackgroundMature cystic teratoma co-existing with a mucinous cystadenocarcinoma is a rare tumor that few cases have been reported until now. In these cases, either a benign teratoma is malignantly transformed into adenocarcinoma or a collision tumor is formed between a mature cystic teratoma and a mucinous tumor, which is either primarily originated from epithelial-stromal surface of the ovary, or secondary to a primary gastrointestinal tract tumor. The significance of individualizing the two tumors has a remarkable effect on further therapeutic management.Case presentationIn this case, a mature cystic teratoma is co-existed with a mucinous cystadenocarcinoma in the same ovary in a 33-year-old Iranian female. Computed Tomography (CT) Scan with additional contrast of the left ovarian mass suggested a teratoma, whereas examination of resected ovarian mass reported an adenocarcinoma with a cystic teratoma. A dermoid cyst with another multi-septate cystic lesion including mucoid material was revealed in the gross examination of the surgical specimen. Histopathological examination revealed a mature cystic teratoma in association with a well-differentiated mucinous cystadenocarcinoma. The latter showed a CK7−/CK20 + immune profile. Due to the lack of clinical, radiological, and biochemical discoveries attributed to a primary lower gastrointestinal tract tumor, the immune profile proposed the chance of adenocarcinomatous transformation of a benign teratoma.ConclusionsThis case shows the significance of large sampling, precise recording of the gross aspects, histopathological examination, immunohistochemical analysis, and the help of radiological and clinical results to correctly diagnose uncommon tumors.

Clinicopathological characteristics of mucinous carcinoma of the breast.

Objective: To highlight clinicopathological differences between Pure Mucinous Carcinoma (PMC) and Mixed Mucinous Carcinoma (MMC) of the breast. Study Design: Descriptive Retrospective study. Setting: Private Lab in Faisalabad, Pakistan. Period: January 2017 to December 2022. Methods: FNAC smears diagnosed with Mucinous Carcinoma fulfilling the inclusion and exclusion criteria were carefully examined for features such as cellularity, extracellular mucin (ECM), nuclear pleomorphism, plasmacytoid cells, macrophages, and myxovascular fragments (MVFs). The diagnosis was confirmed by histopathology and were characterized in to PMC and MMC. Immunohistochemistry slides were evaluated according to established protocols. Statistical analysis was performed using SPSS (p < 0.05). Results: The study analyzed 16 FNAC cytological samples with subsequent histopathological confirmation. These cases were derived from a pool of 712 female breast carcinoma cytology cases over a five-year duration. The predominant age group was 40 to 50 years, with the left breast and upper outer quadrant being the most common site. Distinct cytological characteristics, particularly the significant presence of extracellular mucin in PMC, were observed. Tumor grade and lymph node involvement emerged as crucial prognostic factors. MMC exhibited a high Ki-67 index, indicating increased cellular proliferation. Conclusion: Pure mucinous carcinomas (PMCs) are uncommon breast tumors with distinguished cytologic features. It is clinically and genetically distinct from mixed mucinous carcinoma (MMC) and other types of breast cancer. An important prognostic factor is lymph node involvement, and PMCs often have a low proliferation rate and a more favorable long-term prognosis. Therefore, the identification of PMC through FNAC holds significant diagnostic and clinical importance.

Imaging Diagnosis of Thoracic Elastofibroma Dorsi.

Elastofibroma dorsi (ED) is an uncommon benign tumor that is commonly incidentally discovered on thoracic imaging and at times misinterpreted as a more aggressive lesion. The objective of the study is to characterize the typical cross-sectional imaging findings of elastofibroma dorsi and quantify the risk of masquerading malignancy. Retrospective search of radiology and pathology reports over a 12-year period identified 409 cases of suspected ED. Pertinent imaging was reviewed with a focus on computed tomography (CT) and magnetic resonance imaging (MRI), specifically assessing lesion location, presence of interspersed fat, and appearances on follow-up. Typical imaging appearances of 310 ED, including 10% with pathologic confirmation, were that of a mass deep to the serratus anterior (98%) and near the scapular tip (98%). Intralesional interspersed fat was present in 87% of cases imaged with CT and in 90% of cases imaged with MRI. In the 43 cases imaged with both modalities, 8 (19%) did not have interspersed fat on CT, but 7 (88%) of these did have interspersed fat on MRI. Twelve tumors (benign and malignant) were included, of which only 17% were deep to serratus anterior and 25% were at the scapular tip, P = 0.0001 and P < 0.0001 versus ED. Only a single tumor contained interspersed fat, P < 0.001 versus ED, which had benign pathology on biopsy. Elastofibroma dorsi can be diagnosed with a high degree of certainty in the presence of classic location and imaging characteristics, obviating the need for further imaging or biopsy.

Aggressive angiomyxoma of female pelvis and perineum: Retrospective study of 17 cases

ObjectiveAggressive angiomyxoma is an uncommon mesenchymal neoplasm characterized by a high recurrence rate, usually observed in the lower genital tract of women during their reproductive age. Study designSeventeen cases of aggressive angiomyxoma confirmed by pathology from January 2007 to December 2021 in Beijing Chao-yang Hospital were included. We collected clinical data and summarized the clinical and immunohistochemical features. ResultsAll seventeen included patients were females, aged between 23 and 57 years (mean, 37.7 years; median, 42 years). Fourteen patients were newly diagnosed and three were recurrent. The tumor is located in vulva (58.8 %), vagina (23.5 %), buttock (11.8 %), and cervix (5.9 %). The tumors size was 2 to 15 cm in greatest dimension (mean 8 ± 4.4 cm, median 6 cm). Follow-up data was available for nine patients, which ranged from 25 to 124 months (mean, 82 months; median, 80 months). At the end of follow-up, no other recurrence or metastasis was reported. Immunohistochemical analysis showed immunoreactive for estrogen (10/11) and progesterone (8/11) receptor, desmin (6/8), smooth muscle actin (4/10), and vimentin (4/4), S-100 (1/8) and CD34 (1/7). The Ki67 level was less than 5 % in five cases. ConclusionsAAM is a hormone-sensitive, distinct rare mesenchymal neoplasm with high incidence of local recurrence. Surgery is the preferred treatment, with complete resection being an essential prerequisite for minimizing the risk of recurrence.

A Rare Tumor of Intravascular Myopericytoma in the Right Renal Vein.

Myopericytoma, a perivascular myoid neoplasm, is commonly found in the dermis or subcutaneous tissues; however, its occurrence in visceral organs is unusual. Here, we present an extremely rare tumor of intravascular myopericytoma of the right renal vein. A 44-year-old man was incidentally diagnosed with a mass in the right kidney during a routine checkup. A nephrectomy was performed because the urologist suspected renal cancer. A gross examination of the resected specimen revealed a well-circumscribed brown mass in the renal hilum. Histologically, the tumor showed a concentric multilayered proliferation of spindle cells surrounding blood vessels. Immunohistochemical staining showed that the spindle-shaped tumor cells were negative for desmin but positive for α-smooth muscle actin and h-caldesmon, indicating their myoid nature. We confirmed that the tumor was located in the right renal vein because it was encased within a thick wall that was desmin-positive and contained elastic fibers, as shown by Elastica van Gieson staining. The patient was diagnosed with an intravascular myopericytoma of the right renal vein. There are several differential diagnoses for renal mesenchymal tumors, including angiomyolipoma. This emphasizes the importance of considering these uncommon tumors when examining nephrectomy specimens.

A rare case malignant granular cell tumor of the thigh with radiological imaging likely rhabdomyosarcoma: A case report

Granular cell tumors (GCTs) are uncommon soft tissue tumors characterized by the cytoplasmic granular appearance of the neoplastic cells. Malignant GCTs are rare neural tumors, intensely aggressive. Both the rare occurrence of malignant GCTs and its similarities in features with their benign lesions make the diagnosis of this malignancy difficult. Malignant GCTs comprise less than 2% of GCTs and are mostly found in the subcutaneous soft tissues of the lower extremities, especially the thighs. This article presents a case of a large malignant GCTs in the left thigh of a 46-year-old woman. Plain radiograph of the left thigh demonstrated a soft tissue mass without bone involvement. MRI images showed a malignant solid mass 7.8 x 5.2 x 21.6 cm, with ill-defined border, irregular edges, and suspected rhabdomyosarcoma. Incisional biopsy of the mass lesion revealed mixed epithelioid and spindle tumors, suspected malignant GCTs. Histological examination performed by a musculoskeletal pathologist, demonstrated nests and sheets of epithelioid to polygonal cells with hyperchromatic, intensely eosinophilic granular cytoplasm, prominent nucleoli, increased mitotic activity, necrosis, areas of spindling with significant atypia, and positive for S100 by immunohistochemistry. In conclusion, this patient with malignant soft tissue tumor demonstrated polygonal and spindle cells with eosinophilic granular cytoplasm, which need to be considered diagnosed as Malignant GCTs. This case stresses the importance of thorough histological examination in the diagnosis of malignant GCTs.

Chondroblastoma of the anterior process of calcaneus: a case report

Chondroblastoma of the calcaneus is a fairly uncommon tumour. Despite being a benign and indolent lesion, chondroblastoma of the calcaneus can lead to functional limitations, due to its location in such a weight-bearing bone. This report presents a rare case of chondroblastoma affecting the anterior process of the calcaneus, which was successfully treated with extended curettage and synthetic bone graft substitute, resulting in favourable functional outcomes at 13 months post-surgery. This case underscores the importance of timely recognition and appropriate management of this uncommon tumour to achieve optimal patient outcomes.

Prognostic factors of adrenocortical carcinoma in children and adolescents: a population-based study.

Adrenocortical carcinoma (ACC) is an uncommon adrenal gland endocrine tumor that has a poor prognosis in children. We aimed toconducta population-based cohort study to predict overall survival (OS) in pediatric patients with ACC. We used the Surveillance, Epidemiology, and End Results (SEER) database to conduct a retrospective cohort research on pediatric patients diagnosed with ACC between 1975 and 2018.We examined demographic characteristics, tumor stage and size, treatment options, and survival results. Kaplane-Meier estimations were used to generate survival curves based on several parameters. To compare survival curves, the log-rank test was applied.Cox proportional-hazards regression was used to determine the variables related with OS. In addition, we created a nomogram to predict overall survival in pediatric ACC patients. A total of 143 pediatric ACC patients were identified. Females were the most impacted (60.8%). Overall 1year, 3year, and 5year survival rates were 75.0%, 57.6%, and 53.7% for all patients, respectively. In comparison to older patients (5-19years), younger patients (≤ 4years) were shown to have more positive characteristics, including a higher likelihood of local disease (29.4% vs. 14%, P < 0.001), tumors less than 10cm (23.1% vs. 14.7%, P < 0.001), and improved overall survival (5year OS 89.6% vs. 27.7%, P < 0.001). Age at diagnosis, SEER stage, and surgery were significant independent predictors of OS in this model, according to the results of Cox proportional hazard regression. After that, we developed a nomogram for predicting OS in children with ACC. Patients older than 4years old had a higher chance of dying. Furthermore, the higher the SEER stage, the higher the risk of death. Patients who do not have surgery have a worse survival rate than those who do. Our study revealed that age at diagnosis, SEER stage, and surgery were found to be the most important predictors of the overall survival of pediatric ACC. These findings contribute to the existing body of knowledge and emphasize the importance of continued research to advance our understanding of pediatric ACC and improve patient care.

Epidural angioleiomyoma: an extraordinary cause of compressive myelopathy-MRI findings with histopathological correlation.

Angioleiomyomas are benign mesenchymal tumors usually located in the limbs, with anecdotal reports in the spine. We present an atypical case of an epidural spine angioleiomyoma presenting with compressive myelopathy symptoms. The diagnosis was suggested based on MRI findings, and subsequently confirmed histopathologically. This is the first known occurrence of pure spinal epidural angioleiomyoma as a source of compressive myelopathy. The imaging presentation, especially the 'dark reticular sign' on MRI, was crucial in suggesting the diagnosis despite the atypical location CONCLUSION: This report serves to raise awareness among clinicians and radiologists about including angioleiomyoma in differential diagnoses for spinal epidural lesions with indicative MRI features. The favorable outcome aftersurgical intervention underscores the necessity of swift and accurate diagnosis followed by appropriate treatment for such uncommon spinal tumors.

Desmoplastic fibroma of the pediatric cranium with CTNNB1 mutation: case report and literature review.

Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature. A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg). Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.

The "Other" Uterine Mesenchymal Neoplasms: Recent Developments and Emerging Entities.

Uterine mesenchymal neoplasms are a challenging group of tumors that often show overlapping morphologic features and immunohistochemical profiles. The increasing use of molecular testing in these tumors has enabled a better appreciation of their pathobiology, resulting in a wave of emerging neoplasms and improved characterization of ones previously considered exceptionally rare. Identification of specific molecular alterations has permitted targeted therapy options in tumors that were typically unresponsive to conventional therapies, as well as recognition that a subset can have a hereditary basis. This review will discuss the more "common" of the uncommon uterine mesenchymal neoplasms, including inflammatory myofibroblastic tumor, perivascular epithelioid cell tumor, uterine tumor resembling ovarian sex cord tumor, and embryonal rhabdomyosarcoma. This will be followed by an overview of emerging entities, including NTRK-rearranged uterine sarcoma, SMARCA4-deficient uterine sarcoma, KAT6B/A::KANSL1 fusion uterine sarcoma, and MEIS1::NCOA2/1 fusion sarcoma.

Ameloblastic fibroma of mandible- A case report

Ameloblastic fibromas are uncommon mixed benign odontogenic tumors with an overall prevalence of less than 5%. Asymptomatic uniloular lesions can be effectively managed with curettage, multilocular lesions require meticulous enucleation to avoid the risk of relapse. We report a case successful management of an asymptomatic multilocular ameloblastic fibroma with 2 years of follow up.

SOX-10 and TRP-1 expression in feline ocular and nonocular melanomas.

In felines, ocular and nonocular melanomas are uncommon tumors that represent a diagnostic challenge for pathologists, especially when amelanotic. To date, the immunohistochemical diagnostic panel in cats is based on specific melanocytic markers (Melan-A and PNL2) and a nonspecific but sensitive marker (S100). In human medicine, SOX-10 is reported to be a sensitive antibody for the detection of melanoma micrometastasis in the lymph node. TRP-1, an enzyme involved in melanogenesis, has recently been used in humans and dogs as a specific melanocyte marker. The aim of this study was to evaluate the cross-reactivity and the expression of SOX-10 and TRP-1 antibodies in feline normal tissue and melanocytic tumors. Thirty-one cases of ocular, cutaneous, and oral melanomas were retrospectively evaluated and confirmed by histopathological examination and by immunolabeling with Melan-A and/or PNL2. SOX-10 nuclear expression in normal tissues was localized in epidermal, subepidermal, hair bulb, and iridal stromal melanocytes and dermal nerves. In melanomas, nuclear expression of SOX-10 was detected in ocular (11/12; 92%), oral (6/7; 86%), and cutaneous sites (12/12; 100%). TRP-1 cytoplasmic immunolabeling in normal tissue was observed in epidermal and bulbar melanocytes and in the lining pigmented epithelium of the iris and in its stroma. Its expression was positively correlated to the degree of pigmentation in the tumor and was observed in 75% of ocular (9/12), 43% of oral (3/7), and 33% of cutaneous melanomas (4/12). This study demonstrated the cross-reactivity of SOX-10 and TRP-1 antibodies in feline non-neoplastic melanocytes and their expression in ocular and nonocular melanomas.

Giant clear cell acanthoma: a case report and a review of the literature

Clear cell acanthoma (CCA) is an uncommon benign epidermal tumor of unknown origin and etiology. It is often solitary, and the presence of multiple CCAs in the same individual is rare. Typically, it presents as a slowly growing plaque or nodule located on the legs with a peripheral scaling collarette. Diagnosis is primarily based on clinical and histopathological findings, with dermoscopy enhancing diagnostic accuracy. The differential diagnosis includes various skin tumors and inflammatory dermatoses. The preferred treatment is surgical excision, as these lesions do not regress spontaneously. We describe a case of a large CCA on the right thigh associated with multiple small nodular lesions scattered across the legs.

A Systematic Review of the Epidemiology, Clinical Characteristics, Treatment, and Outcomes for Desmoplastic Trichoepithelioma: Underscoring Mohs Micrographic Surgery in Management.

Desmoplastic trichoepithelioma (DTE) is an uncommon benign adnexal tumor that histologically may mimic malignant tumors including basal cell carcinoma and microcystic adnexal carcinoma. To present a systematic review of the epidemiology, clinical characteristics, treatment, and outcome data on DTEs, with emphasis on comparing Mohs micrographic surgery (MMS) with other treatments. Using the OVID platform, MEDLINE and Embase were searched from inception for studies providing original data on DTEs. A total of 338 cases of DTE from 61 articles were included. No recurrence/persistence (0%) was reported following MMS (n = 24, mean follow-up of 41.9 months), 13.1% with standard excision (n = 38, mean follow-up 16.9 months), and 2.1% for electrosurgery/cautery (n = 49, follow-up 3-72 months). 100% recurrence/persistence for imiquimod (n = 2) and liquid nitrogen (n = 4) were identified. In patients who underwent biopsy only, there was a 12.5% recurrence/persistence (n = 32, mean follow-up 16.5 months). Overall, duration of follow-up varied from 2 months to 6 years for the various management strategies. Data are limited regarding DTE outcomes. In this review, surgical modalities, specifically MMS, had the lowest rates of recurrence/persistence compared with other options. Given that most lesions are found on cosmetically sensitive locations, MMS seems to be the optimal management strategy for actively managing DTEs.

Gastric mixed neuroendocrine non-neuroendocrine neoplasms.

The uncommon tumour known as gastric mixed neuroendocrine-non-neuroendocrine neoplasms (G-MiNENs) is made up of parts of neuroendocrine carcinoma and adenocarcinoma. The biological and clinical features are different from those of gastric adenocarcinoma. Their pathophysiology, diagnostic standards, and clinical behaviour have all been the subject of lengthy debates, and their nomenclature has undergone multiple changes. Its emergence has created new challenges in the classification and diagnosis of gastric tumours. This review will update information on the topic, covering molecular aspects, diagnostic criteria, treatment, and prognostic factor discovery. It will also provide a historical context that will aid in understanding the evolution of the idea and nomenclature of mixed gastric tumours. Additionally, it will provide the reader a thorough understanding of this difficult topic of cancer that is applicable to real-world situations.

Guidelines for Pathologic Diagnosis of Mesothelioma.

Mesothelioma is an uncommon tumor that can be difficult to diagnose. To provide updated, practical guidelines for the pathologic diagnosis of mesothelioma. Pathologists involved in the International Mesothelioma Interest Group and others with expertise in mesothelioma contributed to this update. Reference material includes peer-reviewed publications and textbooks. There was consensus opinion regarding guidelines for (1) histomorphologic diagnosis of mesothelial tumors, including distinction of epithelioid, biphasic, and sarcomatoid mesothelioma; recognition of morphologic variants and patterns; and recognition of common morphologic pitfalls; (2) molecular pathogenesis of mesothelioma; (3) application of immunohistochemical markers to establish mesothelial lineage and distinguish mesothelioma from common morphologic differentials; (4) application of ancillary studies to distinguish benign from malignant mesothelial proliferations, including BAP1 and MTAP immunostains; novel immunomarkers such as Merlin and p53; fluorescence in situ hybridization (FISH) for homozygous deletion of CDKN2A; and novel molecular assays; (5) practical recommendations for routine reporting of mesothelioma, including grading epithelioid mesothelioma and other prognostic parameters; (6) diagnosis of mesothelioma in situ; (7) cytologic diagnosis of mesothelioma, including use of immunostains and molecular assays; and (8) features of nonmalignant peritoneal mesothelial lesions.