In 1952, Christopherson and colleagues described the distinctive clinical and pathologic features of alveolar soft part sarcoma (ASPS). For nearly half a century, controversy raged regarding the putative cell of origin of this peculiar neoplasm. Following the identification of the characteristic der(17)t(X;17)(p11;q25) translocation and discovery of the resulting ASPSCR1::TFE3 gene fusion in 2001, the current consensus is that alveolar soft part sarcomas represent one of several gene fusion-driven sarcomas which lack a normal cellular counterpart. This updated review highlights the clinical and pathologic features of this intriguing neoplasm.

Perivascular cell tumors (PEComas) in the genitourinary tract have an overwhelming propensity to occur in the kidney, where they are synonymously referred to as angiomyolipomas (AMLs). Although less common, PEComas may occur throughout the urinary tract (particularly involving the bladder) and may rarely appear in the prostate/seminal vesicle and testis. Herein, we describe the wide clinicopathologic characteristics of genitorurinary PEComas both of renal and extrarenal origin.

The Dublin ISUP Consensus Conference covered the proceedings on the best practice recommendations on nonurachal glandular lesions of the urinary bladder, bladder diverticular cancers, and molecular features of bladder and urachal glandular lesions. The conference proceedings on urachal neoplasms (except for their molecular features) are published elsewhere. The rationale for convening this conference was the lack of structured and consented pathologic recommendations in these rare lesions. Consensus by participants was reached on the following statements: (1) intestinal metaplasia with dysplasia is considered to be a precursor to primary bladder adenocarcinoma; (2) dysplasia arising from cystitis glandularis should be reported in terms of focality (focal or nonfocal) and grade (low or high); (3) the term "adenocarcinoma" should only be used for carcinomas showing pure (nonurothelial) morphology and should not be used interchangeably in urothelial carcinoma with "glandular differentiation" because of the pathobiological differences and management implications; (4) the different histologic subtypes of bladder adenocarcinoma should be specified in the report; (5) immunohistochemistry has an ancillary role in the work up of bladder adenocarcinoma versus gastrointestinal or Müllerian-type adenocarcinomas; (6) lymphovascular invasion should be included as a parameter when reporting bladder adenocarcinoma; (7) representative or targeted sampling will be sufficient for bladder diverticulum resection specimens; and (8) molecular analysis in genomic profiling should be performed only in advanced or metastatic bladder and urachal adenocarcinomas for targetable therapy. This report on glandular (nonurachal) lesions of the bladder from the Dublin ISUP consensus conference will serve as a best practice recommendation and as a guide for future research on these relatively rare lesions.

Drug-induced liver injury (DILI) has an incredible range of morphologic presentations, from acute extensive necrosis to resolving injury with ceroid-laden macrophages. The diversity in presentation on biopsy is diagnostically challenging, but DILI is becoming more widely recognized, especially with the aid of resources like LiverTox. Some medications, such as acetaminophen, have well-established patterns of injury. However, newer medications, such as immune checkpoint inhibitors, are continually being developed, and our understanding of their effects on the liver are evolving. In this chapter, we will focus on the DILI patterns and frequently encountered DILI culprits. Ultimately, DILI is a diagnosis of exclusion, and close clinical correlation is essential when navigating the differential.

BRCA1-associated protein-1 (BAP1) tumor predisposition syndrome is due to germline mutation of BAP1, a tumor suppressor gene. Patients with this syndrome has an increased susceptibility to the development of uveal melanomas, cutaneous melanomas, cutaneous atypical melanocytic lesions, mesotheliomas, clear cell renal cell carcinoma, and other tumors. These syndromic tumors exhibit an aggressive growth and earlier onset in comparison to sporadic tumors. In this review we outline the history, epidemiology, and genetics of this syndrome. The clinical presentation and histopathology of commonly developed tumors in syndromic patients, namely uveal melanomas, cutaneous atypical melanocytic lesions, mesotheliomas, and clear cell renal cell carcinoma are discussed.

There are inherited germline variants that predispose patients to select mesenchymal tumors with associated tumor syndromes. While many of these tumors are clinically suspected or diagnosed early in life, pathologists can play a critical role in their initial recognition and reporting, prompting appropriate confirmatory testing and follow-up for the affected patient and screening for their family members. Hereditary conditions commonly encountered in association with bone and soft tissue pathology include Hereditary Multiple Osteochondromas, Familial Adenomatous Polyposis, Carney Complex, and Neurofibromatosis Type I. Additional syndromes include Rhabdoid Tumor Predisposition Syndrome, Familial Schwannomatosis, DICER1 syndrome, and others. Herein, we describe select bone and soft tissue tumors associated with familial syndromes, aiming to provide a guide for practicing surgical pathologists on how to recognize these lesions and when they should raise the possibility of an associated hereditary condition.

A wide spectrum of tumors can affect the gynecologic tract in the context of hereditary cancer syndromes. Over the past two decades, the approach to germline testing initiated by pathologic findings has evolved considerably. This shift began with the identification and integration of specific tumor characteristics and molecular pathways in the most common hereditary syndromes involving the female genital tract, namely, hereditary breast and ovarian cancer syndrome and Lynch syndrome. Subsequently, tumors linked to less common syndromes, such as Peutz-Jeghers syndrome, DICER1 syndrome, tuberous sclerosis complex, hereditary leiomyomatosis and renal cell carcinoma syndrome, and rhabdoid tumor predisposition syndrome type 2 have also been recognized. This review focuses on the clinicopathologic features of these hereditary conditions, with particular emphasis on histologic patterns and genetic testing.