American Journal of Surgical Pathology最新文献

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.

Oral tongue squamous cell carcinoma (OTSCC) is the most common cancer of the oral cavity. A new histopathologic risk assessment has been recently introduced and we sought to validate its prognostic value in a large multicenter cohort of early-stage OTSCC. A total of 310 cases treated for early-stage OTSCC were included in this study. The assessment of modified worst pattern of invasion and a recently developed tumor budding score were performed in hematoxylin and eosin-stained sections. A statistically significant association was observed in the multivariable analysis between high score of the new risk model and worse disease-specific survival (HR: 2.54, 95% CI: 1.48-4.37, P <0.001). Similarly, in disease-free survival, the high-risk group was significantly associated with poor survival (HR: 1.66, 95% CI: 1.07-2.58, P =0.024). In conclusion, the new histopathologic risk model is a powerful prognostic indicator and can be assessed as part of routine diagnostic practice. Early-stage OTSCC patients with a high-risk score have a poor prognosis and therefore require a multimodality treatment strategy with a close clinical follow-up.

The current American Joint Committee on Cancer (AJCC) pT classification was inaccurate in predicting prognosis for perihilar cholangiocarcinoma (pCCA). This study aimed to propose a novel classification based on the depth of liver invasion (DOLI) of pCCA. Patients who underwent major hepatectomy combined with caudate lobectomy for pCCA between January 2015 and June 2023 were reviewed retrospectively. The maximum straight-line distance from the hepatic hilar plate to the infiltrated liver parenchyma was measured as DOLI. Log-rank statistics were used to determine the cutoff points. Among 167 patients, liver invasion was observed in 100 patients (59.9%). The cutoff points of DOLI for prognosis were 0 mm and 2.5 mm. DOLI was stratified into grade 1 (DOLI=0 mm; 67/167, 40.1%), grade 2 (0 mm2.5 mm; 37/167, 22.2%). The DOLI grade was associated with CA19-9 levels, tumor size, lymph node metastasis, perineural invasion, and portal vein invasion. The DOLI grade was an independent prognostic factor for both overall survival (OS) and recurrence-free survival (RFS) (both P <0.001), and demonstrated superior prognostic discrimination compared with the pT classification (C-indexes for OS and RFS: 0.67 vs. 0.63; 0.64 vs. 0.61). In conclusion, DOLI was an accurate prognostic indicator for pCCA. The 3-tier DOLI grades with cutoff points of 0 and 2.5 mm may serve as a potential alternative to the current pT classification.

The classification and diagnosis of penile intraepithelial neoplasia (PeIN) remains inconsistent among pathologists, despite its recognized role and understanding as a precursor to penile squamous cell carcinoma (PSCC). The International Society of Urological Pathology (ISUP) convened a consensus group of multidisciplinary thought leaders to assess current global practices regarding the usage of terminology, grading, and molecular testing in penile cancer precursor lesions. A preconference survey was distributed to ISUP members in 2024, collecting responses from 112 pathologists, predominantly genitourinary specialists, to evaluate the use of penile cancer precursor lesion classification systems, grading approaches, and diagnostic biomarkers. The results were presented at the ISUP Multidisciplinary Consensus Conference on Cancer Precursor Lesions in September 2024, where further consensus was achieved through electronic voting. The survey revealed that 89.4% of respondents classify PeIN based on HPV association, with 76% supporting further subtyping into basaloid, warty, and differentiated subtypes. Grading of PeIN remains controversial; 51.3% initially favored grading, but 82% finally voted that PeIN should not be graded. p16 immunohistochemistry (IHC) was widely utilized (91.5%) to distinguish HPV-associated from HPV-independent PeIN, whereas p53 IHC and HPV genotyping lacked consensus for routine use. Reporting practices for PeIN margins and their association with lichen sclerosis were widely endorsed, while the value and concordance of subtyping HPV-independent PeIN remains an area for further investigation. This ISUP consensus paper guides PeIN classification, confirming the importance of HPV-related stratification and p16 IHC staining and reporting as standard practice. However, significant variability persists in PeIN grading and molecular testing strategies. These findings highlight the need for further research and standardization to optimize diagnostic accuracy and clinical relevance in PeIN.

Inverted papilloma (IP) is a benign neoplasm of the nasal cavity and paranasal sinuses, known for its variable risk of recurrence and potential for developing carcinoma. Emerging evidence has shown high rates of activating EGFR mutation, and a smaller subset is associated with low-risk human papillomavirus (lrHPV). While certain morphologic features, including an inverted growth pattern, are well-established, the presence of condylomatous features, such as large fungating lesions with thick undulating surface epithelium, hyperkeratosis, cytoplasmic clearing, raisinoid nuclei, and binucleation (koilocytic changes) in low-risk HPV-associated IP suggests that these tumors may be a distinct subtype of sinonasal papilloma (SP) with features similar to low-risk HPV-associated anogenital condylomas. This study presents a series of SP with condylomatous morphology and explores the association with lrHPV, the clinicopathologic features, and the rates of carcinoma development. In total, 17 cases of SP exhibiting condylomatous morphology were retrospectively identified. We performed lrHPV and high-risk HPV (hrHPV) RNA in situ hybridization and p16 immunohistochemistry and gathered detailed clinical and pathologic data along with treatment, disease follow-up, and outcomes. These condylomatous papillomas almost all developed in active smokers, were large, were primarily located in the nasal cavity (47%), and showed frequent transformation to invasive squamous cell carcinoma (29%). This malignant transformation rate is much higher than what has been reported for inverted, exophytic, and oncocytic papillomas. The tumors were almost uniformly associated with transcriptionally-active lrHPV (94%) and were consistently negative for p16 and hrHPV. This study shows that a subgroup of IPs with condylomatous morphology have a predilection for the nasal cavity, strong association with lrHPV, and high rates of carcinoma. These findings support the concept that these tumors are a distinct (fourth) type of SP with a higher risk of malignant transformation.