American Journal of Surgical Pathology最新文献

Primary Ewing sarcoma (ES) of the kidney is rare. We describe the clinicopathologic features of primary renal ES with emphasis on gene fusion partners. A multi-institutional study was conducted to obtain clinicopathologic data on primary ES of the kidney. All tumors with available tissue underwent NGS to determine fusion partners. Twenty-four patients (8 male, 16 female) were identified. Mean age was 33.2 (±12.3). Mean tumor size was 10.5 cm (±4.2). Clinical presentation was available in 21 patients: flank/abdominal pain (13, 61.9%), hematuria (4, 19%), mass (2, 9.5%), hypertension (1, 4.8%), and incidental (1, 4.8%). For 23 nephrectomies, 2 (8.7%) were ypT0 (post-neoadjuvant therapy), 3 (13%) pT1, 15 (65.2%) pT2, 1 (4.4%) pT3, and 2 (8.7%) pT4. Four (16.7%) had metastatic disease at presentation. Of 18 patients with available follow-up, 9 (50%) were alive with disease, 7 (38.9%) alive with no disease, and 2 (11.1%) died of disease (mean follow-up 34 mo). Metastatic disease was documented in 9/18 patients, including lung (3), adrenal (2), bone (2), retroperitoneum (2), liver (2), lymph node (1), and ureter (1). FISH was performed in 14 tumors and real-time quantitative PCR in 1, confirming EWSR1 rearrangements. NGS was performed in 17 tumors, showing EWSR1::FLI1 in 16 (94.1%) and EWSR1::ETV4 in 1. Primary renal ES is a rare neoplasm occurring in a wide age range. Most tumors invaded adjacent tissues. Although they share similar histologic and molecular features with their counterpart in the bone/soft tissue, we document the first case of a rare EWSR1::ETV4 fusion in the kidney.

Primary large B-cell lymphoma of immune-privileged sites (IP-LBCL) is a newly categorized disease entity in the 5th WHO Classification of Tumors. Through an analysis of 53 primary adrenal large B-cell lymphoma (PA-LBCL) cases, we unraveled the similarity to IP-LBCL in clinical presentation, pathologic features, and genetic landscape. Our findings reveal a predominant immunophenotype of CD10-/BCL6+/MUM1+ in PA-LBCL, mirroring that observed in IP-LBCL, and a shared mutation spectrum characterized by the notable presence of PIM1, MYD88 L265P, and CD79B mutations. In addition, the results of RNA sequencing showed that there are significant differences in the expression profiles of PA-LBCL and SA-LBCL. The top 5 RNAs with the most significant expression differences were RPL23AP82, IGSF21, CMKLR, PTPRG, and PRKCA. Moreover, PA-LBCL exhibited a more favorable prognosis than DLBCL-NOS with secondary adrenal involvement. The results of this study indicate that PA-LBCL shares similar clinical features, immunophenotypes, and molecular genetic profiles with IP-LBCL, suggesting that it may belong to a subtype of IP-LBCL. This research has improved our understanding of lymphoma, especially those occurring in atypical sites, and reshaped our concept of lymphoma classification and management. We suggest considering incorporating PA-LBCL into IP-LBCL in the future classification of lymphoma.

IDH1 mutant prostatic adenocarcinoma represents a small fraction of prostate cancer with distinct epigenetic changes, characterized by genome-wide DNA hypermethylation. Recently, prostatic adenocarcinoma with intratumoral psammomatous calcifications was found to frequently harbors IDH1 R132 mutations. However, the association with IDH1 hotspot mutations and psammomatous calcifications in prostate cancer remains controversial. Here we report another rare case of IDH1 R132H mutant prostatic adenocarcinoma, showing intratumoral psammomatous calcifications identified in targeted needle biopsies as well as subsequent radical prostatectomy specimen. This case provides independent evidence for identification of IDH1 mutant prostate cancer by combined histologic features, including intratumoral psammomatous calcifications, anterior tumor location, and high Gleason score. In addition, to our knowledge, this is the first case of multifocal prostate cancer reported in the literature, with the co-existence of spatially disparate and genetically distinct tumor foci harboring IDH1 R132H mutation or TMPRSS2 - ERG gene fusion in the same prostate.

Transbronchial cryobiopsies (CB) are increasingly replacing surgical biopsies (video-assisted thoracoscopic/VATS biopsies) for diagnosing diffuse parenchymal lung disease (interstitial lung disease, ILD), but there is very little guidance for pathologists on CB interpretation. Here we propose a fairly simple approach. First, if the diagnosis can be made on a traditional forceps biopsy, it can be made on a cryobiopsy. Many diseases with specific features will fall into this category (eg, sarcoidosis or Langerhans cell histiocytosis). More problematic are patterns such as usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP), in which low-power architecture is the key to diagnosis. In this circumstance, an adequate sample is crucial to look for features such as fibroblast foci, because a combination of fibroblast foci plus any patchy old fibrosis, fibrotic architectural remodeling, or honeycombing, allows a diagnosis of a UIP pattern. However, in most instances, CB will not separate the UIP patterns seen in idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis, or connective tissue disease-interstitial lung disease (CTD-ILD), although giant cells/granulomas (uncommon findings) in this setting favor fibrotic hypersensitivity pneumonitis. Fibroblast foci can be difficult to differentiate from organizing pneumonia (OP), but granulation tissue plugs clearly in airspaces favor OP. Absent fibroblast foci, patchy old fibrosis, architectural distortion, and honeycombing by themselves do not allow a specific diagnosis. NSIP in CB microscopically looks like NSIP in VATS biopsies, and the presence of an NSIP or an NSIP+OP pattern is typical of CTD-ILD. All the above diagnoses require correlation with clinical and radiologic findings.

Seborrheic keratosis-like lesion (SKLL) is an extremely rare, morphologically distinct lesion occurring in the cervix and vagina that differs histologically from other squamous intraepithelial lesions in these sites due to its unique morphology, including close resemblance to cutaneous seborrheic keratosis and lack of viral cytopathic effect (koilocytosis). We report a series of 17 cases, describe in detail the morphology and add to the evidence linking SKLL with low-risk human papillomavirus (LRHPV), specifically HPV42, which was detected in 13 cases; in 3 cases, an additional single HPV type (HPV6, 16, 61) was detected. In 2 of the SKLLs, a component of high-grade morphology and block-type p16 immunoreactivity were observed, prompting speculation as to the oncogenic potential of HPV42. Nineteen cases of papillary immature metaplasia, another distinctive LRHPV-associated lesion with some morphologic overlap with SKLL, were HPV42 negative. Independently, HPV42 has recently been implicated as the cause of a rare, aggressive cutaneous tumour, digital papillary adenocarcinoma (DPA), with experimental molecular data supporting the transforming capacity of this virus. These findings, along with the observation that rare anogenital squamous cell carcinomas are associated with HPV42, demonstrate the rare carcinogenic potential of this LRHPV. The association of HPV42 with these 2 unique and distinctive tumours (SKLL and DPA) also illustrates the incompletely understood diversity of HPV genotype-phenotype associations and virus-host interactions and highlights the importance of HPV typing of novel genital and cutaneous tumours.

Dedifferentiated solitary fibrous tumor (DDSFT) is a rare and clinically aggressive malignancy with a poor prognosis. It represents the progression of solitary fibrous tumor to a high-grade, morphologically nondistinctive sarcoma. This study characterizes the clinicopathologic and molecular features of 25 DDSFT. The study cohort comprised 13 males and 12 females with a median age of 63 years (range 31 to 84). Tumors were most common in the pelvic cavity (8/25), thoracic cavity (6/25), and trunk (4/25). Histologically, DDSFT demonstrated remarkably variable morphology, including pleomorphic, epithelioid, spindle cell, and round cell features. Heterologous elements were present in 4/25 (16%). Immunohistochemical expression of STAT6 was completely lost in 8/22 (36%) tumors. Targeted DNA sequencing demonstrated that in most tumors (10/13; 77%), the NAB2 :: STAT6 fusion variant resulted in a truncated STAT6 (STAT6-TAD) in the fusion protein. Recurrent secondary alterations involved TP53 (10/14; 71%), TERT (8/14; 57%), and RB1 (3/14; 21%). Statistical analysis of the study cohort and 55 cases reported in the literature demonstrated that complete loss of STAT6 in DDSFT is associated with shorter disease-specific survival (HR 12.69, P =0.023).

Gastric-type intraductal papillary neoplasm of the bile duct (G-type IPNB) remains an underexplored subtype of IPNBs, with limited molecular characterization. This study aimed to elucidate the clinicopathologic and genomic features of G-type IPNB to better understand its malignant potential and progression. Eighty-three IPNB cases, including 21 G-type IPNBs, were analyzed. The clinicopathologic features and prognosis of G-type IPNB were compared with those of other subtypes. Targeted sequencing was performed in 15 G-type cases, comprising 5 with high-grade dysplasia (HGD), 6 with invasive carcinoma (INV), and 4 with lymph node metastasis (LNM). The samples displayed varying histologic grades. The G-type frequently exhibited HGD; however, invasive G-type IPNBs showed significantly higher rates of lymph node metastasis compared with the other subtypes ( P =0.044). Recurrent mutations were detected in KRAS (60%), STK11 (40%), KMT2C (40%), APC (20%), CTNNB1 (13%), and TP53 (13%). Mutational profiles remained highly concordant across histologic grades, with no significant new mutations accumulating during tumor progression. KRAS mutations were predominantly found in preinvasive lesions, supporting their role in early tumorigenesis. STK11 mutations were exclusive to INV and LNM cases, but not detected in HGD cases. Notably, identical mutations were uniformly carried over from preinvasive lesions to invasive carcinoma and metastatic lymph node lesions. Immunohistochemically, aberrant STK11 expression was specific to the G-type compared with other subtypes ( P =0.030). These findings highlight the unique clinicopathologic and molecular features of G-type IPNB, including the association of STK11 mutations with invasive behavior and their potential as indicators of tumor progression.

A portion of the fimbriated end of the fallopian tube known as the fimbria ovarica extends along the lateral edge of the mesosalpinx to the ovary to which it is attached at its lateral pole. Seventy-four examples of fimbrial plicae that were attached to the ovary or broad ligament and lacked features of adhesions were studied. The fimbrio-ovarian attachments were characterized by one or more of the following: continuity between the tubal epithelium and either the ovarian surface epithelium, peritoneum, or both, in 51 cases; direct continuity of the ovarian stroma into the stroma of the fimbria ovarica in 42 cases; and direct insertion of plicae into the ovarian surface or ovarian stroma in 18 cases. In 21 cases, there was a direct attachment of plicae to the broad ligament close to the ovary. The mean size of the fimbria ovarica was 6.6 mm. The plicae were lined by normal tubal-type epithelium. The plical morphology was typically abnormal displaying one or more of the following features: short and blunted in 24 (32%), thickened in 18 (24%), elongated in 14 (19%), fusion in 13 (18%), edema in 13 (18%), and fibrosis in 11 (15%). Also noted were a mesothelial component in 69 cases (93%), the tubal-peritoneal junction in 53 cases (72%), transitional cell metaplasia/Walthard cell nests in 11 cases (15%), and foci resembling incipient fimbrial adenofibroma in 7 cases (9%). An understanding of the microanatomy and histology of the fimbria ovarica has important implications, particularly as: (a) portions may be left behind after prophylactic salpingectomy, providing a nidus for future development of high grade serous carcinoma (HGSC); (b) it constitutes an anatomic connection that may facilitate the spread of HGSC to the ovary, and (c) epithelial junctions are hotspots for carcinogenesis, and stem cells arising in such regions may be a source of HGSCs. In addition, understanding the fimbria ovarica has implications for the pathogenesis of ovarian surface epithelial inclusions, endosalpingiosis, and certain types of infertility. Its potential role as a site of origin of extrauterine HGSC, which typically arises in the fimbriae as serous tubal intraepithelial carcinoma, remains to be investigated.