Additional Histologic Features Research Articles

HPB P16 How relevant are additional histological features when predicting five-year recurrence/survival rates afterpancreatoduodenectomy for ampullary adenocarcinoma? Results from the Recurrence After Whipple’s (RAW) study

Abstract Background Providing they have an appropriate performance status, patients with ampullary adenocarcinoma (AA) may be offered pancreatoduodenectomy (PD) with curative intent. Aggressive histological tumour characteristics are known to correlate with poor long-term outcomes. This study aimed to quantify how peripancreatic fact invasion (PPFI), perineural invasion (PNI), microvascular invasion (MVI) and lymphatic invasion (LI) correlate with five-year recurrence and five-year survivalrates. Methods Data were extracted from the Recurrence After Whipple’s (RAW) study, a multicentre retrospective cohort study of outcomes of PD performed for pancreatic head malignancy (29 centres in 8 countries, n=1484). Patients with histologically confirmed AA were identified and compared by their PPFI, PNI, MVI and LI statuses. Fisher’s exact test was used for the comparisons. Results A total of 394 patients (26.5%) had AA confirmed. Incidence rates of PPFI, PNI, MVI and LI were 37.8%, 46.1%, 45.2% and 58.6%, respectively. Five-year recurrence was significantly higher in patients demonstrating PPFI (58.9% vs 34.3%, p=0.0005), PNI (56.6% vs 34.0%, p=0.0001), MVI (60.2% vs 34.2%, p<0.0001) and LI (54.7% vs29.2%, p<0.00001). Five-year survival was significantly lower in patients with PPFI (29.4% vs 62.9%, p<0.0001), PNI (40.4% vs 64.8%, p<0.0001), MVI (43.0% vs 61.3%, p=0.003) and LI (44.1% vs 65.0%, p<0.0005). Patients with PPFI, PNI, MVI and LI were significantly more likely to have histological T3-4 disease (vsT1-2, all p<0.0001). Conclusions In our multicentre study of AA patients who underwent PD, less than half had histological evidence of PPFI, PNI or MVI, but a majority had LI. All of these features were associated with increased recurrence and reduced survival rates. However, this likely reflects the fact that these features all correlate with more advanced histological disease.

Histomorphological Patterns of Focal Segmental Glomerulosclerosis and Their Clinical Correlation in Tertiary Care Hospitals in Bangladesh

Background: Being one of the commonest glomerular diseases in adults and a major etiology of the nephrotic syndrome, Focal Segmental Glomerulosclerosis (FSGS) gradually progresses towards end-stage renal disease (ESRD). According to pathogenesis, FSGS can be classified into primary or secondary ones and in both instances, histomorphological findings are nearly indistinguishable. Five histomorphological variants of primary as well as secondary focal segmental sclerosis have already been accepted, for instance, NOS (not otherwise specified), tip, cellular, perihilar, and collapsing variants. Nonetheless, primary FSGS is a diagnosis of exclusion and all the time, primary and secondary FSGS can not be distinguished discernibly. For this reason, correlation with clinical and biochemical parameters are extremely important. The present study was undertaken to identify various histomorphological patterns of FSGS by light microscopy and immunofluorescence study at tertiary care hospitals in Bangladesh as well as to correlate those patterns with clinical, biochemical parameters and additional histologic findings. Methods: This is an observational & cross sectional study which was conducted among 57 paraffin blocks of renal biopsy specimens of histologically confirmed FSGS cases including all age groups and both sexes, which were collected from department of Pathology, BSMMU & Kidney foundation hospital & research institute, Mirpur, Dhaka. Renal biopsies received for light microscopy only and biopsies that contained less than eight glomeruli were exluded from the study . Routine Haematoxylin & Eosin (H&E), Periodic Acid Schiff (PAS), Jones silver & Masson’s trichrome stains were used to evaluate renal biopsy specimens & histomorphological patterns of FSGS were identified. Data regarding clinical & biochemical parameters were collected from patient’s medical records. Statistical analyses were performed by SPSS-22. Result: In our study, it was observed that, among 57 biopsies, 35(61.4%) biopsies were diagnosed as NOS, 12(21.1%) biopsies as perihilar, 4(7.0%) biopsies as tip, 3(5.3%) biopsies as collapsing and 3(5.3%) biopsies as cellular variant. No clinical and biochemical parameters were significantly associated with these histomorphological patterns of FSGS. Regarding additional histologic features, thick walled blood vessels was significantly associated with histomorphological patterns. Conclusion: This study was conducted on only two tertiary level hospitals in Bangladesh, therefore, the result may not reflect the exact scenario of Bangladesh. It is the need of the moment to mention the histomorphological patterns of FSGS in renal histopathology reports. Moreover, logistic support is a necessity to institute nephro-pathology section in the pathology department of all the tertiary care hospitals in order to identify renal glomerular disease precisely. Sir Salimullah Med Coll J 2023; 31: 26-33

The Frequency and Diagnostic Value of Deeper Sections in Histopathology of Non-Cutaneous Small Biopsy Specimens Obtained from a Tertiary Care Hospital

Objective: The purpose of this research is to ascertain the frequency of deeper sections and the diagnostic utility of these sections in non-cutaneous tiny biopsies obtained from a hospital setting. Study Design: Cross-sectional study Place and Duration: This study was carried out at Shaukat Khanum Memorial Hospital Peshawar, Jan 2022 to April 2022 Methods: In this study, there were a total of 100 patients, ranging in age from 16 to 50 years old. Patients who were hospitalized to the oral and maxillofacial department and who had deeper section procedures were considered for inclusion. Following the acquisition of informed and written consent, complete demographic information was obtained. The locations of organs and the levels at which leaks were found were documented for each and every instance. The mean, standard deviation, frequency, and percentages were the metrics that were used to evaluate the categorical variables. All of the data was analysed with SPSS version 22.0. Results: Among the deeper sections, we discovered that cervix cases accounted for 50%, stomach cases accounted for 25%, endometrial cases accounted for 15%, and colorectal cases accounted for 10%. Twenty-six instances 26%, had a deeper section done, with level 4 being the most prevalent. Although in most cases a diagnosis could be determined from the initial slide, in 55 of these cases (55%), further slides were reviewed to look for additional histological features. The goal was to either confirm the diagnosis obtained from the initial slide or raise confidence in that diagnosis. In 55 cases, 39 (70.9%) showed new pathological abnormalities in deeper sections, whereas 16 (29.1%) showed no change in histological features. Conclusion: A more in-depth examination is typically required in order to arrive at a certain diagnosis. Because of this, it is recommended that, regardless of the extent of the lesion, deeper sections be conducted on samples that cannot be consistently detected on ordinary levels, and this approach need to be standardized everywhere in the globe. Keywords: Histopathology, Deeper Sections, Non-cutaneous, Biopsy

Automated Prediction of Kidney Failure in IgA Nephropathy with Deep Learning from Biopsy Images.

Digital pathology and artificial intelligence offer new opportunities for automatic histologic scoring. We applied a deep learning approach to IgA nephropathy biopsy images to develop an automatic histologic prognostic score, assessed against ground truth (kidney failure) among patients with IgA nephropathy who were treated over 39 years. We assessed noninferiority in comparison with the histologic component of currently validated predictive tools. We correlated additional histologic features with our deep learning predictive score to identify potential additional predictive features. Training for deep learning was performed with randomly selected, digitalized, cortical Periodic acid-Schiff-stained sections images (363 kidney biopsy specimens) to develop our deep learning predictive score. We estimated noninferiority using the area under the receiver operating characteristic curve (AUC) in a randomly selected group (95 biopsy specimens) against the gold standard Oxford classification (MEST-C) scores used by the International IgA Nephropathy Prediction Tool and the clinical decision supporting system for estimating the risk of kidney failure in IgA nephropathy. We assessed additional potential predictive histologic features against a subset (20 kidney biopsy specimens) with the strongest and weakest deep learning predictive scores. We enrolled 442 patients; the 10-year kidney survival was 78%, and the study median follow-up was 6.7 years. Manual MEST-C showed no prognostic relationship for the endocapillary parameter only. The deep learning predictive score was not inferior to MEST-C applied using the International IgA Nephropathy Prediction Tool and the clinical decision supporting system (AUC of 0.84 versus 0.77 and 0.74, respectively) and confirmed a good correlation with the tubolointerstitial score (r=0.41, P<0.01). We observed no correlations between the deep learning prognostic score and the mesangial, endocapillary, segmental sclerosis, and crescent parameters. Additional potential predictive histopathologic features incorporated by the deep learning predictive score included (1) inflammation within areas of interstitial fibrosis and tubular atrophy and (2) hyaline casts. The deep learning approach was noninferior to manual histopathologic reporting and considered prognostic features not currently included in MEST-C assessment. This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_07_26_CJN01760222.mp3.

Prognostic significance of additional histologic features for subclassification of pathological T3 colon cancer

BackgroundAdditional histologic features of T3 colon cancer, such as tumour depth invasion beyond muscularis propria and elastic lamina invasion (ELI), have taken interest for a more accurate staging.MethodsPatients with pT3 and pT4a (control group) colon adenocarcinoma were retrospectively collected from our institutional database. The study group was divided according to depth of tumour invasion < 5 mm and ≥ 5 mm, and into ELI − and ELI + . Chi-square test was used to compare the clinicopathological characteristics. OS and DFS were estimated using Kaplan–Meier method and compared with the log-rank test. Univariable and multivariable Cox proportional hazard models were employed to assess the effect on OS and DFS.ResultsOut of 290 pT3 tumours, 168 (58%) had a depth of tumour invasion < 5 mm and 122 (42%) ≥ 5 mm. The 5-year OS and DFS were 85.2, 68.7 and 60.9%, and 81.4, 73.9 and 60.1% in pT3 < 5 mm, pT3 ≥ 5 mm, and pT4a respectively (p = 0.001, p = 0.072). Considering ELI − (n = 157, 54%) and ELI + (n = 133, 46%), the 5-year OS and DFS were 78.9, 76.7, and 60.9%, and 75.5, 81.5, and 60.1% in ELI − , ELI + and pT4a respectively (p = 0.955, p = 0.462). At multivariable analysis, the depth of invasion was found to be an independent predictive factor for OS (HR 2.04, 95%CI 1.28–3.24, p = 0.003) and DFS (HR 1.98, 95%CI 1.24–3.18, p = 0.004), while ELI did not result a prognostic factor for OS nor DFS.ConclusionIn pT3 colon cancer, depth of tumour invasion ≥ 5 mm is an independent risk factor for OS and DFS, whereas ELI did not result a prognostic factor affecting OS nor DFS.

Epigenetic and genomic profiling of chordoid meningioma: implications for clinical management

Chordoid meningioma is a morphological variant of meningioma designated as WHO grade 2. However, the recurrence rates varied widely in different case series, and to date, a unifying molecular genetic signature has not been identified. Among 1897 meningiomas resected at our institution, we identified 12 primary chordoid meningiomas from 12 patients. Histologically, all 12 cases had predominant (> 50%) chordoid morphology. Ten were otherwise grade 1, and two were also atypical. We performed DNA global methylation profile, copy number variation analysis, and targeted next-generation sequencing on 11 chordoid meningiomas, and compared to those of 51 non-chordoid, mostly high grade meningiomas. The chordoid meningiomas demonstrated a unique methylation profile in tSNE, UMAP, and hierarchical heatmap clustering analyses of the most differentially methylated CpGs. The most common copy number variation in chordoid meningioma was loss of 1p (7/11, 64%). Three chordoid meningiomas had 2p loss, which was significantly higher than the non-chordoid control cohort (27% vs 7.2%, p = 0.035). 22q loss was only seen in the two cases with additional atypical histological features. Chordoid meningiomas were enriched in mutations in chromatin remodeling genes EP400 (8/11,73%) KMT2C (4/11, 36%) and KMT2D (4/11, 36%), and showed low or absent NF2, TERT, SMO, and AKT1 mutations. Prognosis wise, only one case recurred. This case had atypical histology and high-grade molecular features including truncating NF2 mutation, 1p, 8p, 10, 14, 22q loss, and homozygous deletion of CDKN2A/B. Progression free survival of chordoid, otherwise grade 1 meningioma was comparable to non-chordoid WHO grade 1 meningioma (p = 0.75), and significantly better than chordoid WHO grade 2 meningioma (p = 0.019). Conclusion: the chordoid histology alone may not justify a universal WHO grade 2 designation. Screening for additional atypical histological or molecular genetic features is recommended.

Subungual melanoma with blue naevus-like morphological features: a clinicopathological retrospective analysis of nine cases

Melanocytic lesions in the nail apparatus are often challenging. Both subungual melanomas (SUM) and blue naevus of the nail are very rare. Occasionally, melanomas may mimic blue naevus histologically. Benign and malignant blue melanocytic lesions are commonly associated with G protein mutations, a distinct abnormality not associated with conventional subungual melanomas. We describe the clinical, histological and immunohistochemical features of nine cases of SUM with blue naevus-like morphological features. Mutations in exon 4 and 5 of GNAQ and GNA11 were investigated in two cases, which showed no mutations. RNA-seq of one case revealed unknown mutations along with mutations in ATM, METK and ARID1A. Our study delineates a variant of SUM that mimics blue naevus. Awareness of this pitfall is important when evaluating heavily pigmented lesions around the nail in order to avoid misdiagnosis. Appropriate sampling of subungual lesions and clinicopathological correlation are paramount to reach the correct diagnosis.

Acetone Compression Improves Lymph Node Harvesting.

To the editor The review article by Díaz del Arco et al1 provides a comprehensive review of the methods used for the surgical removal and gross room retrieval of lymph nodes from gastric carcinoma excisions, TNM staging of gastric carcinoma, and multiple additional histologic features of lymph node metastases used for accurate prognosis of gastric carcinoma. The authors mention methods beyond manual palpation to improve lymph node harvesting, such as fat clearing. Omitted from the comprehensive review is an entirely new method for lymph node harvesting first reported in the United States in 2004.2 This method, currently used more extensively in Germany (the early reports are based on over 700 cases), is the “acetone compression” method for lymph node retrieval.3-5 The acetone compression method decreases adipose tissue volume through dissolving fat in fat solvents (elution) and extracting the dissolved fat with compression. Tissue volume is decreased up...

Diagnostic and therapeutic challenge of unclassifiable enteropathies with increased intraepithelial CD103+ CD8+ T lymphocytes: a single center case series

Objectives Chronic diarrhea, villous atrophy and/or increased intraepithelial T-lymphocytes (IEL) occur in many inflammatory disorders including celiac disease (CD). However, a definite diagnosis is difficult to make in some patients despite an extensive diagnostic work-up. Clinical outcomes and histological phenotypes of such patients we refer to as unclassifiable enteropathy (UEP) remain unclear. Material and methods We performed a retrospective single-center analysis of patients with chronic diarrhea, weight loss and increased IEL. Patients with defined etiologies including infections, CD, drugs, immunodeficiencies or neoplasms were excluded. Clinical and histologic/immunophenotypic parameters were analyzed. Results Nine patients with UEP were identified. Small intestinal damage ranged from minor villous abnormalities to complete atrophy while all patients displayed high numbers of CD103+ CD8+ IELs. In contrast to CD, these CD8+ T cells were not confined to the surface epithelium, but also infiltrated the crypts. Additional histological features included apoptotic crypt epithelial cells and mixed inflammatory infiltrates in the tunica propria. Involvement of other segments of the gastrointestinal tract was observed in 7/9 patients. A clonal intestinal T-cell lymphoproliferative disorder developed in 2 patients, one of which had a fatal disease course. The majority of patients responded to corticosteroids, while response to immunosuppressive medications yielded heterogeneous results. Conclusions We report a patient population with ‘difficult-to-classify’ enteropathies characterized by various degrees of villous atrophy and strongly increased intraepithelial CD103+ CD8+ T cells in the small intestine which harbor an increased risk for T-cell lymphoproliferative disorders. Clinical course, histology, and response to immunosuppressive therapy all suggest an autoimmune pathogenesis.

Histologic Correlates of Molecular Group 4 Pediatric Medulloblastoma: A Retrospective Canadian Review.

The World Health Organization currently classifies medulloblastoma (MB) into four molecular groups (WNT, SHH, Group 3 and Group 4) and four histologic subtypes (classic, desmoplastic nodular, MB with extensive nodularity, and large cell/anaplastic). "Classic" MB is the most frequent histology, but unfortunately it does not predict molecular group or patient outcome. While MB may exhibit additional histologic features outside of the traditional WHO subtypes, the clinical significance of such features, in a molecular context, is unclear. The clinicopathologic features of 120 pediatric MB were reviewed in the context of NanoString molecular grouping. Each case was evaluated for five ancillary histologic features, including: nodularity without desmoplasia (i.e., "biphasic", B-MB), rhythmic palisades, and focal anaplasia. Molecular and histological features were statistically correlated to clinical outcome using Chi-square, log-rank, and multivariate Cox regression analysis. While B-MB (N = 32) and rhythmic palisades (N = 12) were enriched amongst non-WNT/SHH MB (especially Group 4), they were not statistically associated with outcome. In contrast, focal anaplasia (N = 12) was not associated with any molecular group, but did predict unfavorable outcome. These data nominate B-MB as a surrogate marker of Groups 3 and particularly 4 MB, which may earmark a clinically significant subset of cases.

A Modified 2 Tier Chemotherapy Response Score (CRS) and Other Histopathologic Features for Predicting Outcomes of Patients with Advanced Extrauterine High-Grade Serous Carcinoma after Neoadjuvant Chemotherapy.

Simple SummaryReliable predictive indicators of response to neoadjuvant chemotherapy of advanced-stage extrauterine high-grade serous carcinoma are still lacking. Moreover, changes evident in tumor samples from interval surgery are not well understood. Our retrospective study aimed to address the prognostic value of chemotherapy response score (CRS) and identify additional predictive features for the risk of progression and death. In a cohort of 245 patients, we demonstrate that the modified two-tier CRS was prognostic for survival, and this significance was independent of scoring site; our data support expansion of CRS use to the adnexal samples. In addition to the CRS, oncocytic change, inflammation, and desmoplasia were additional histopathologic parameters related to survival. We recommend using the two-tier CRS, together with the additional histological features serving as secondary criteria for scoring, to identify patients at high risk for recurrence, allow tailored adjuvant therapy strategies, or consider clinical trials.Background: The impact of chemotherapy response score (CRS) on prognosis has varied among studies. We addressed the prognostic significance of CRS and the prognostic value of previously undescribed histologic features using a cohort of 245 patients. Methods: Retrospective study in patients with advanced extrauterine high-grade serous carcinomas treated with neoadjuvant chemotherapy followed by interval tumor reductive surgery from 1990 to 2018 in our hospital. Gynecologic pathologists assessed tumor CRS and other histologic features. Clinical information was collected, and multivariate analyses were conducted. Results: A modified 2 tier CRS (CRS 1/2 versus CRS 3) was significantly associated, independent of scoring site (omental versus adnexal), with overall survival (OS) (omentum, p = 0.018; adnexa, p = 0.042; entire cohort, p = 0.002) and progression-free survival (PFS) (p = 0.021, p = 0.035, and p = 0.001, respectively). On multivariate survival analysis, 2 tier CRS, oncocytic change, inflammation, and desmoplasia were significant for OS (p = 0.034, p = 0.020, p = 0.007, and p = 0.010, respectively). Likewise, 2 tier CRS, inflammation, and desmoplasia were significant for PFS (p = 0.012, p = 0.003, p = 0.011, respectively). Conclusions: The modified 2 tier CRS was significantly associated with survival, independent of scoring site. Additional histologic features including oncocytic change, inflammation, and desmoplasia can also predict patient outcomes.

Histomorphological analysis of gastric polyps.

Incidence of gastric carcinoma and gastric polyps is on rise all over the world. Chronic atrophic gastritis to intestinal metaplasia progressing to adenocarcinoma has been documented pathway for gastric carcinogenesis. Another pathway for gastric carcinoma is adenoma carcinoma sequence similar to colon cancer. To study prevalence, endoscopic, and histomorphological features of gastric polyps. This was retrospective analysis of gastric polyps from 2012 to 2019 in consecutive 10,800 upper gastrointestinal endoscopies. Demographic, endoscopic, and histopathological data were obtained from hospital records. All gastric polyps were classified as per standard histologic criteria. Additional histological features noted were presence of dysplasia, focus of adenoma, or malignancy. The prevalence of gastric polyps was 434 (4%) of 10,800 upper gastrointestinal endoscopies. Majority of polyps were found in the last 4 years (277: 63.8%). Mean age was 55.4 years with male to female ratio 1:1.2. Most of the polyps (94.9%) were less than 1 cm, located in gastric antrum. Multiple polyps were seen in 20.9% cases. On histopathology, fundic gland polyps were most common (147: 33.8%), followed by hyperplastic (128: 29.4%) polyps. Adenomatous polyps were nine (2%); of these, two cases of hyperplastic polyps and one each of fundic gland polyp and benign epithelial polyp showed adenomatous foci. Fundic gland polyps were the most common polyps. With rising incidence of gastric carcinoma, identification of gastric polyps on endoscopy with biopsy can prevent progression to carcinogenesis.

P0112BOWMAN'S CAPSULE RUPTURE ON RENAL BIOPSY IMPROVES THE OUTCOME PREDICTION OF ANCA-ASSOCIATED GLOMERULONEPHRITIS CLASSIFICATION

Abstract Background and Aims ANCA-associated vasculitis is the most common cause of rapidly progressive glomerulonephritis (GN) and can lead to ESRD or death, even after aggressive immunosuppressive therapies (Jones et al, N Engl J Med, 363(2010), 211-220). The histological assessment of renal tissue can help in predicting the outcome and a 4-tiered classification based on glomerular lesions has been proposed to stratify these cases (Berden et al, J Am Soc Nephrol, 21(2010), 1628-1636). Subsequent studies, however, failed to confirm its predictive value (Tanna et al, Nephrol Dial Transplant, 30(2015), 1185-1192), stressing the need of new prognostic markers of the disease. The present study investigates whether additional histological features can improve the performance of the current classification in predicting the outcome of these patients. Method A retrospective series of biopsy-proven paucimmune crescentic GN has been collected between January 2012 and June 2018 from two Italian centers (San Gerardo Hospital, Monza and Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma). After the exclusion of patients with negative/unavailable serum ANCA testing, lacking clinical data, less than 12 months of follow-up, less than 5 glomeruli per biopsy and coexisting glomerular diseases, a final cohort of 52 cases was selected. Demographic and clinical data at the time of the diagnosis are reported in Figure, panel A. Renal biopsies have been reviewed by two experts in renal pathology and scored for multiple glomerular, tubulointerstitial and vascular lesions, as well as classified following the 4-tiered schema. The outcome of interest was time to need for RRT or death, whatever occurred first. Cox proportional hazards regression models were constructed with time to composite event, loss to follow-up or censoring (06/30/2019). Time at risk started at the date of renal biopsy. Histologic predictors were collapsed into binary variables (0-1 = low; 2-3 = high) and tested in univariate models, with the association expressed as hazard ratios (HRs) and 95% confidence intervals (CI); those showing a significant association with the outcome ( Figure, panel B) were included in a multivariable model together with a variable representing the Berden class. The prognostic performance of models including only the Berden class or the Berden class plus additional predictors was assessed using Harrell’s c-statistic. Results During a follow-up of 1,828 person-months, 13 composite events developed (8 deaths, 5 RRT), corresponding to an incidence rate of 7.1 (95% CI 4.2, 12.2) per 1,000 person-months. Of the tested predictors, Bowman’s capsule rupture (BCR, Figure, panel C) was significantly associated with the outcome (p = 0.023). Compared with a model including only Berden class (c = 0.67), the addition of this parameter significantly improved the prognostic performance (c = 0.76). In the multivariable model including Berden class, BCR remained significantly associated with the outcome (HR 3.61, 95% CI 1.15, 11.34; p = 0.028). Conclusion The present study demonstrated an improved performance of Berden classification in predicting patients’ outcome after the implementation of BCR. This can allow a better stratification of these cases, leading to tailored therapeutic approaches. Further investigations on a larger prospective cohort are required to confirm these results.

The Significance of Histologically "Large Normal" Parathyroid Glands in Primary Hyperparathyroidism.

We investigated outcomes in a cohort of patients with a biochemical diagnosis of primary hyperparathyroidism (pHPT) undergoing surgery for asymptomatic disease or target organ damage, where a focussed or four-gland operation was undertaken and the histopathology only reported a "large normal" parathyroid gland (LNP). Patients subjected to a parathyroidectomy for pHPT between 2012 and 2018 with a pathology of LNP were included. Patients with fat depletion or additional histological features of adenoma or hyperplasia in any of the resected glands were excluded. A control group was formed from 50 consecutive patients with the histological finding of adenoma or hyperplasia during the same study period. The primary outcome was biochemical normalisation of pHPT at 1-2weeks and after 6 months post-operatively. Forty-eight LNP patients (2% of all parathyroidectomies) were included in the study group with 50 matched controls. LNP patients had a lower biochemical cure rate (81% vs. 98% P < 0.05) and a higher risk of recurrence (10% vs. 0%, P = 0.06). LNP patients had a milder form of pHPT (Ca2+ 2.63 vs. 2.68 P < 0.05) with a smaller PTH and Ca2+ drop post-operatively. For LNP patients with failure, a definite additional cause of pHPT was found in only two patients. This study highlights a controversial area in pHPT and reports LNP as a cause of pHPT. The biochemical analysis of this LNP group supports a benefit in resection in the setting of pHPT, although the risk of failure (persistence/recurrence) is higher than those with adenoma or hyperplasia. Stricter post-operative follow-up of LNP patients should be considered.

Metastatic Crohn Disease: A Clinicohistological Appraisal From a Tertiary Care Center in India.

Granulomatous dermatitis due to noncontiguous involvement of Crohn disease (CD) of the gut has been described as metastatic CD (MCD). MCD is the rarest form of cutaneous manifestations of CD. This study aims to analyze the clinicohistological features of MCD in a tertiary care center of India. A retrospective review of patients diagnosed clinically and histologically with MCD over past 5 years was performed. Data on cutaneous features, histological findings, and response to treatment were collected. Twelve patients (3 men and 9 women) with a mean age of 29 years were identified. All women had vulval involvement in the form of edema (80%), ulceration (60%), and fistula (20%). Among the 3 men, 2 had perineal and scrotal swelling and ulcer, whereas the third patient presented with leg ulcer. Intestinal CD was already diagnosed in 50% patients (5/10) at cutaneous presentation, whereas it was diagnosed subsequently in 30% (3/10) cases. Histological examination revealed nonnecrotizing granulomatous inflammation in the dermis in 11 patients (92%). Additional histological features included eosinophilic infiltrate (58%), panniculitis (33%), and vasculitis (33%). The patients were treated with various combinations of oral prednisolone, metronidazole, minocycline, azathioprine, and subcutaneous adalimumab with partial relief. MCD shows a wide spectrum of clinical presentation, with anogenital involvement being the most common. Histology reveals nonnecrotizing granulomas in the dermis in majority of the cases. The diagnosis is extremely challenging in patients without gastrointestinal involvement at presentation, and thus, a high index of suspicion is imperative.

Cervical Adenocarcinoma: Histopathologic Features From Biopsies to Predict Tumor Behavior.

The pattern-based classification system of endocervical adenocarcinoma correlates with nodal metastasis and clinical outcomes, but its application in biopsies is challenging. The aim of this study was the correlation of additional histologic features with patterns of invasion as well as prognosis. A total of 103 specimens from 71 cervical adenocarcinoma cases were studied. Among the 71 cases, all had resection specimens including hysterectomy, cold knife cone excision or loop electrosurgical excision procedure excision, and 32 of these had prior cervical biopsies. We applied the pattern-based classification system to all the specimens and evaluated histopathologic features microscopically. Findings in biopsies were compared with their corresponding resections and correlated with nodal status and disease stage. In 71 resection specimens, pattern A was present in 10 (14.1%), pattern B in 12 (16.9%), and pattern C in 49 (69%) cases. Of the 32 cervical biopsies, pattern of invasion could be classified in only 16 (50%) cases, including 1 (6%) with pattern A, 4 (25%) with pattern B, and 11 (69%) with pattern C. Of the 32 cervical biopsies, 30 could be evaluated for intraluminal necrotic/tumor debris and/or grade 3 nuclei, which correlated with pattern C as well as with lymph node metastasis in the subsequent staging specimens. No tumor with patterns A or B had intraluminal necrotic/tumor debris or grade 3 nuclei in either biopsy or resection specimens. Therefore, intraluminal necrotic/tumor debris and grade 3 nuclei are highly predictive histologic features for cervical adenocarcinomas with pattern C invasion and nodal metastasis.

Predicting Outcome in Mammary Phyllodes Tumors: Relevance of Clinicopathological Features.

Phyllodes tumors (PTs) of the breast are uncommon fibroepithelial neoplasms. Most behave in a benign fashion but they also have the potential to recur locally or to metastasize. In the current study involving 290 PTs (181 benign, 76 borderline, and 33 malignant) from three hospitals over an 11-year period, we assessed the relationship between histologic parameters (including histologic features affecting grade and surgical margin status), postoperative adjuvant treatment, and local recurrences and distant metastases. An involved surgical margin was the only factor associated with increased risk of local recurrences (hazard ratio [HR] 4.673, p = 0.003), but not for distant metastases. For local recurrences, a wider margin did not confer additional benefits. None of the histologic factors were predictive for local recurrences. In contrast, distant metastases were correlated with histologic parameters, particularly an infiltrative border (HR 10.935, p = 0.012) and the presence of necrosis (HR 15.311, p = 0.007). In this series, all local recurrences were found in patients without radiotherapy, regardless of surgical margin status. A negative surgical margin is mandatory for the effective local control of PT recurrence, and a minimal margin clearance may be sufficient. For distant metastases, the inherent characteristics of PTs are important, thus it may be prudent to evaluate additional histologic features, including necrosis, for patients' prognostication.

Evaluation of histologic changes in the livers of patients with early and late hepatic artery thrombosis

Hepatic artery thrombosis (HAT) following orthotopic liver transplantation (OLT) can cause hepatic parenchymal necrosis and ischemic cholangiopathy. This study investigates additional histologic features that may suggest HAT in post-OLT liver specimens. For 94 liver specimens (explanted allografts and biopsies) from patients with a clinical or pathologic diagnosis of HAT, we recorded length of time between OLT and procedure, categorizing cases into early HAT (;≤30 days since OLT) and late HAT (>30 days since OLT). Common histologic findings in HAT included lobular necrosis (60 cases, 64%), portal inflammation (68 cases, 72%), ductular reaction (73 cases, 78%), lobular cholestasis (70 cases, 74%), and bile-tinged macrophages (40 cases, 43%). Ductular cholestasis was seen in 30 cases (32%); 10 of those patients were clinically septic. Bile in veins was seen in 16 (17%) cases and arteritis in 6 (6%) cases. Findings more common in resection than biopsy specimens included lobular necrosis (P < .0001), hemorrhage (P = .0044), ductular cholestasis (P = .0003), and bile-tinged macrophages (P < .0001). Lobular necrosis was more common in early HAT (P = .0002), and ductular reaction (P = .006) and bile in veins (P = .03) were more common in late HAT. Histologic changes in HAT vary based on specimen type and whether HAT is early or late. In late HAT, biliary injury might occur after a prolonged period of ischemia, with subsequent bile duct necrosis, bile in veins, and remodeling (eg, ductular reaction). Bile in veins is an unusual finding that may occur in HAT, although it can be seen in bile infarcts from other causes.

Clinically Relevant Prognostic Parameters in Differentiated Thyroid Carcinoma.

Although differentiated thyroid carcinomas typically pursue an indolent clinical course, it is important to identify the subset of tumors that are most likely to behave aggressively so that patients with these tumors are counseled and treated appropriately. Extent of disease is fundamental to the prognostication for differentiated thyroid carcinoma; however, there are additional histologic features of the tumor separate from extent of disease that have been shown to affect clinical course. This review will start with a discussion of aggressive variants of papillary thyroid carcinoma, move to the prognostic significance of vascular invasion in follicular thyroid carcinoma, and finish with a discussion of Hürthle cell carcinoma, with an emphasis on why it is not considered a subtype of follicular thyroid carcinoma in the 2017 WHO Classification of Tumors of Endocrine Organs.

Analysis of the Histologic Features Associated With Interobserver Variation in Idiopathic Pulmonary Fibrosis.

The histologic manifestation of idiopathic pulmonary fibrosis (IPF) is usual interstitial pneumonia (UIP), which is a good prognostic determinant of survival compared with other histologic interstitial lung disease patterns. According to the current international guidelines, the histologic features of suspected IPF/UIP are divided into 4 categories: UIP, probable UIP, possible UIP, and not UIP pattern. Four pulmonary pathologists who were blinded to clinicoradiologic information reevaluated 50 surgical lung biopsies (83.3%), 6 lung explant (10.0%), and 4 autopsy samples (6.7%) from the FinnishIPF registry (N=60) using the current diagnostic guidelines. Additional histologic features atypical for UIP were also evaluated and compared with clinicora-diologic information. The interobserver agreement of pathologists was examined by Cohen kappa (κ) coefficient; the survival of the patients was estimated with Kaplan-Meier curves. The histologic reevaluation indicated that 38 of 60 patients (63.3%) had definite UIP. Inflammation was the most common additional histologic finding (15/60, 25.0%). The interobserver agreement on histologic diagnosis ranged from slight (κ=0.044) to substantial (κ=0.779). The interobserver agreement varied extensively with regard to the presence of giant cells. The observed histologic features displayed no association with radiologic patterns or survival. Definite UIP and honeycombing findings in high-resolution computed tomography correlated with poor prognosis. A high level of interobserver variability was observed between pathologists, even in this well-defined cohort of IPF patients, which highlights the importance of multidisciplinary decision making in IPF diagnostics and stresses the need for a reassessment of the histologic criteria.