Annals of Diagnostic Pathology

Metastases from uveal melanoma may lack S100 expression: A clinico-pathologic and immunohistochemical study with emphasis on potential causes and diagnostic implications
Salzano S, Vecchio GM, Failla M, Russo A, Avitabile T, Longo A, Caltabiano R and Broggi G
Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, with a high mortality rate due to metastasis, primarily to the liver. The differential diagnosis of metastatic UM, particularly in distinguishing it from cutaneous melanoma (CM), can be challenging due to overlapping histopathological features. This study investigates the immunohistochemical expression of S100 in a cohort of 41 cases, including 13 metastatic UMs, 18 metastatic CMs, and 10 primary UMs. Our results demonstrate a significant lack of S100 immunoreactivity in metastatic UM, with 84.6 % of cases showing negativity, in contrast to the diffuse positivity seen in both primary UM and metastatic CM. This finding suggests that the absence of S100 could serve as a useful marker to differentiate metastatic UM from CM, especially in cases where the primary tumor is unknown. Furthermore, the study highlights the potential diagnostic pitfall of relying solely on S100 expression on small biopsies. The absence of S100 in metastatic UM may reflect a shift in antigenic expression, possibly due to tumor dedifferentiation or clonal selection of S100-negative cells with a higher metastatic potential. Our findings emphasize the importance of employing a comprehensive immunohistochemical panel, including markers such as HMB45, SOX10, and Melan-A, in the accurate diagnosis of metastatic melanomas.
Molecular classification of medulloblastoma using immunohistochemistry: A single centre study
Harry JL, Shezi NB and Mwazha A
Medulloblastoma (MB) is the second most common malignant paediatric central nervous system (CNS) tumour. The World Health Organisation (WHO) advocates an integrated pathological and molecular approach to diagnosis. Immunohistochemistry (IHC) has been proven to be a valid surrogate for molecular subtyping in low resource settings. This study aimed to use IHC to classify MB into different molecular subtypes. Patients diagnosed with medulloblastoma between 2011 and 2021 were included in the study. Clinicopathological characteristics, treatment patterns and outcomes were reviewed. Molecular subgrouping into wingless signalling activated (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH was performed by immunohistochemical staining, using β-catenin, Yes-associated protein 1 (YAP1) and GRB2-Associated Binding Protein 1 (GAB1) antibodies. Of the 32 children evaluated, the mean age at diagnosis was 9.9 years with M: F ratio of 1.5:1. Classic (75.8 %) and desmoplastic/nodular (24.2 %) were the only two histopathological variants reported. Non-WNT/non-SHH constituted the majority of cases (54.5 %), followed by SHH (36.4 %) and WNT subgroups (9.1 %). The 5-year overall survival and 5-year progression-free survival was 41 % and 38 % respectively. The 30-day operative mortality rate was 28.1 %. Molecular subgroups determined by immunohistochemistry, can be easily incorporated into routine practice in low resource settings. The overall survival rate in our cohort is lower than thate reported in the literature due to high post-operative mortality and low uptake of adjuvant oncotherapy.
Development of a digital algorithm for assessing tumor-stroma ratio, tumor budding and tumor infiltrating lymphocytes in vulvar squamous cell carcinomas
Baandrup L, Kjær SK, Jacobsen Ó, Bzorek M, Eriksen TT, Larsen LG and Fiehn AK
Tumor-stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) are prognostic markers in some cancers but with unknown significance in vulvar squamous cell carcinoma (VSCC). This pilot study primarily aimed to develop a digital method for evaluating TSR, TB and TILs in VSCC and secondarily to investigate variation in these factors by p16 status. An independent training set stained with CD3/cytokeratin and CD8/cytokeratin was used to develop a deep learning-based Application Protocol Package (APP) segmenting tissue into background, epithelium, or stroma. TSR was defined as percentage of tumor epithelium relative to total tumor area, and tumor buds were defined as clusters of 1-4 tumor cells. A second APP quantified CD3+ and CD8+ lymphocytes in the intraepithelial and stromal compartments, respectively. The digital algorithms were applied to the study cohort of 41 VSCC cases, achieving satisfactory performance without manual corrections. TSR ranged between 33 and 91% with median of 64%, and median number of buds was 4 (range: 0-48) buds/mm. Median density and range of CD3+ lymphocytes were 222 (13-2320) cells/mm in the intraepithelial and 1978 (397-6683) cells/mm in the stromal compartment, respectively. CD8+ lymphocyte counts were lower. There was a tendency towards lower TSR and higher number of buds in p16-negative compared with p16-positive VSCC. Finally, automated measures were compared with manual evaluations showing high concordance. The developed automated method provided precise and objective measurements of TSR, TB and TILs. The algorithms should be validated in a larger cohort and correlated with clinicopathological characteristics and prognosis to determine their clinical relevance.
Acellular mucin in non-neoplastic inflammatory conditions of lower gastrointestinal tract
Fu Z, Park E, Aydin HB, Shrestha N, Yang LM, Dabaghian A and Lee H
In the context of neoplasia, acellular mucin in lower gastrointestinal (GI) tract implies occult mucin-producing tumor and warrants additional workup. The clinical significance of acellular mucin in benign conditions remains unclear.
Brachyury expression is highly specific for chordoma: A tissue microarray study involving 14,976 cancers from 135 different tumor types and subtypes
Caneve P, Schraps N, Möller K, Büyücek S, Lutz F, Chirico V, Viehweger F, Reiswich V, von Bargen C, Kind S, Menz A, Kluth M, Hube-Magg C, Bernreuther C, Sauter G, Marx AH, Simon R, Krech T, Steurer S, Fraune C, Minner S, Gorbokon N, Lennartz M, Burandt E, Rico SD, Freytag M and Luebke AM
Brachyury protein plays a role in defining the midline of bilaterian organisms. Commonly expressed in chordomas, brachyury immunohistochemistry is used to distinguish chordomas from their differential diagnoses. However, brachyury expression has also been described to frequently occur in other cancer entities. To better comprehend the role of brachyury expression in cancer, a tissue microarray containing 14,976 samples from 135 different tumor entities and 608 samples of 76 different normal tissue types were analyzed by immunohistochemistry. Brachyury staining was found in 55 (0.44 %) of the 12,409 interpretable tumor samples, including 37 (0.3 %) with weak, 10 (0.08 %) with moderate, and 8 (0.06 %) with strong positivity. Brachyury staining strongly predominated in chordomas. Of ten chordomas, 7 were strongly and 3 moderately positive. Only 5 of the 134 analyzed further tumor categories showed brachyury staining, 4 of which originated from testicular germ cells. Brachyury positivity occurred in 21.4 % of 42 yolk sac tumors, 15.2 % of 46 embryonal carcinomas, 4.4 % of 562 seminomas, and 2.4 % of 41 teratomas of the testis. Our data support the previously suggested high specificity of brachyury for chordoma detection, and demonstrate that germ cell tumors represent the only additional group of unrelated cancer entities expressing brachyury at a significant level.
Pitfalls and considerations in the diagnosis of Hirschsprung's disease: A focus on pathological assessment
Afshari F
Hirschsprung's disease (HSCR) is a congenital disorder of the intestine characterized by the absence of ganglion cells (GCs) in the myenteric and submucosal plexuses of the distal colon, leading to functional obstruction. The diagnosis of HSCR relies heavily on histopathological examination, yet pitfalls abound. Underdiagnosis can lead to delayed diagnosis, the need for reoperation, or risk of complications; conversely, overdiagnosis can lead to unnecessary surgery and its associated side effects. This comprehensive pictorial review addresses common diagnostic challenges using cases from our hospital, a tertiary pediatric facility and referral center for HSCR patients, and emphasizes the need for close cooperation among pathologists, surgeons, pediatric gastroenterologists, and radiologists to achieve optimal management for patients with HSCR.
Correlation of hsa-mirna-342-3p and SOX 6 Expression with Diabetic Nephropathy Classification, Prognostic Histomorphological Parameters and Laboratory Findings in Diabetic Nephropathy
Arslan G, Karabulut YY, Yeleser İ, Erdal ME, Demir S and Özdemir AA
Diabetic nephropathy (DN) is one of the leading causes of end-stage renal disease. The most popular biomarkers in current research on DN are microRNAs. There are studies showing that while the expression of SOX6 increases, hsa-miR-342-3p expression decreases in kidney tissues with DN. The current study evaluated hsa-miR-342-3p expression by Real Time PCR and SOX6 expression by immunohistochemistry in a cohort of 110 DN biopsies, as well as their relationship with various clinical and histomorphological parameters. An inverse relationship between expression of hsa-miR-342-3p and SOX6 was demonstrated. SOX6 genetic expression was correlated with serum creatinine and tubular basement membrane thickening. Immunohistochemically, SOX6 staining was observed in mesangial cells and podocytes in 21 patients, with tubular staining in 45, and interstitial staining in 27 patients. Tubular staining was associated with proteinuria, interstitial fibrosis and inflammation; interstitial staining was associated with creatinine; and staining in the glomerular compartment was associated with advanced DN class. Our study is the first in the literature in which SOX6 was applied immunohistochemically in human kidney tissue, and its relation with DN classes was examined. We demonstrate its correlation with laboratory and histomorphological parameters, and provide a rational basis for future studies on larger patient groups that may result in the development of new biomarkers to predict the progression of DN and enhance its treatment.
GPNMB expression differentiates subependymal giant cell astrocytoma from other mimickers
Pan R, Wang X, Fang R, Xia Q, Wang X, Zhang R, Wei X, Wu N and Rao Q
Subependymal giant cell astrocytomas (SEGAs) are neoplasms that exhibit slow growth patterns and are closely associated with tuberous sclerosis complex (TSC). Recent research indicates that TFE3/TFEB-targeted biomarker glycoprotein nonmetastatic B (GPNMB) is upregulated inTSC1/2-related tumours. In this study, we performed molecular analysis on SEGAs and analyzed GPNMB expression in 6 SEGAs, 10 PXAs, 9 GBMs, 8 eGBMs, 8 diffuse astrocytomas, 8 oligodendrogliomas and 7 glioneuronal tumours through immunohistochemistry, 100 % (6/6) of the SEGA cases exhibited positive GPNMB expression, whereas it was negative in all other CNS tumours. The results indicated that GPNMB is specifically expressed in all SEGAs, distinguishing it from other morphologically similar tumours. The findings demonstrate specific GPNMB expression in SEGA, underscoring its promise as a diagnostic biomarker.
Clinicopathological and prognostic significance of stromal p16 and p53 expression in oral squamous cell carcinoma
Amano Y, Hasegawa M, Kihara A, Matsubara D, Fukushima N, Nishino H, Mori Y, Inamura K and Niki T
The tumor microenvironment is highly heterogeneous and consists of neoplastic cells and diverse stromal components, including fibroblasts, endothelial cells, pericytes, immune cells, local and bone marrow-derived stromal stem and progenitor cells, and the surrounding extracellular matrix. Although the significance of p16 and p53 has been reported in various tumor types, their involvement in the stromal cells of oral squamous cell carcinoma (OSCC) remains unclear. We performed immunohistochemical analyses of p16 and p53 expression in OSCC samples, Of the 116 samples, 74 showed p16-positive stromal cells, and 33 showed p53-positive stromal cells. Both p16 and p53 positivity were associated with an increased histological grade, lymphovascular invasion, an immature stromal pattern with abundant amorphous extracellular matrix material, infiltrative invasion patterns (Yamamoto Kohama classification-4C and 4D), and poor prognosis. Multivariate analyses identified p16 and p53 positivity in the stroma as independent prognostic factors for overall survival (P = 0.032 and P = 0.020, respectively); moreover, stromal p16 positivity correlated with stromal p53 positivity. These findings indicated that p16 and p53 stroma positivity may regulate OSCC tumor aggressiveness.
Digital image analysis of tumour pattern and histological models for prognostic evaluation of invasive non-mucinous adenocarcinoma of the lung
Tirasarnvong W and Kanjanapradit K
The 2021 World Health Organisation classification of lung adenocarcinoma is based on the predominance and percentage of high-grade histological patterns, e.g. solid and micropapillary patterns, determined by semiquantitative estimation. Digital pathology can be used to evaluate the area of each pattern and calculate the exact percentage. To evaluate the prognostic predictive ability of a histological model for invasive non-mucinous adenocarcinoma using digital pathology. This retrospective cohort study included 76 patients with invasive non-mucinous lung adenocarcinoma who underwent lung resection at Songklanagarind Hospital between January 2010 and December 2016. The histological pattern area was measured on a digital slide using the QuPath Open software version 0.3.2. Clinical and pathological data, including the presence of tumour spread through airspaces, tumour necrosis, tumour-infiltrating lymphocytes, and lymphovascular invasion, were collected. The primary outcome was 5-year overall survival. The best model was provided by the Akaike information criterion, and the prognostic discrimination ability was compared with that of other models from previous studies by identifying the area under the curve (AUC) in the receiver operating characteristic analysis. The best model was validated using bootstrapping. The best model was a combination of stage and an 82 % cut-off high-grade pattern (AUC = 0.776). Tumours with ≥82 % high-grade pattern resulted in significantly worse prognoses (p = 0.001) than those with <82 % high-grade pattern. Our model had the highest AUC among all models from previous studies. This was validated using bootstrapping, with an AUC of 0.708. The best model for survival prediction was a combination of stage and an 82 % cut-off high-grade pattern.
Assessing the predictive value of Ki-67 and progesterone receptor algorithms for recurrence and disease-free survival in meningiomas
Guresci S, Aydogdu OB, Secen AE and Uzel B
Sophisticated refinements in histopathology are evolving to improve meningioma outcome prediction. The aim of this study is to evaluate the stand-alone performance of Ki-67 and progesterone receptor (PR) algorithm scores in meningiomas and their power in predicting recurrence and disease-free survival of the patients. Whole slide images of Ki-67 and PR-stained slides from 404 meningioma cases were analyzed by a digital image viewer and analysis software Virapath-2.1, which analyzes the tumor cells by size, color, and shape. Ki-67 scores were calculated in the hotspot region that contains at least 1000 tumor cells, while PR was calculated on the whole slide. The results were compared with WHO grade, tumor recurrence and disease-free survival (DFS). Mean Ki-67 scores were 4.2 ± 3.5, 12.1 ± 10.6 and 22. ± 8.5 for grade 1, 2 and 3 tumors (p < 0.05), while PR scores were 49 ± 35, 43 ± 34 and 16 ± 30, respectively (p > 0.05). Median survival of patients based on Ki-67 values ≤13.2 % and > 13.2 % was 122 versus 60 months (p = 0.004). Prediction of recurrence based on Ki-67 score was found to have acceptable discrimination (AUC = 0.74). PR expression was not found to correlate with DFS, but recurrent tumors had lower PR scores than non-recurrent tumors (31.3 ± 33.8 vs. 49.0 ± 33.0; p = 0.03). Elevated Ki-67 levels identified by the algorithm may classify meningioma patients at high recurrence risk and inform clinical management. Although PR scores did not correlate with DFS, lower expression in recurrent tumors suggests a role in recurrence risk assessment. Larger prospective studies are needed for routine clinical practice.
The diagnostic utility of SOX11 Immunohistochemical expression in malignant peripheral nerve sheath tumors and their potential mimickers
Tasar Kapakli E, Pekmezci M, Katipoglu K, Soylemezoglu F, Gedikoglu G, Tihan T and Kosemehmetoglu K
Malignant peripheral nerve sheath tumor (MPNST) comprises 5-10 % of all soft tissue sarcomas, and their diagnosis may be challenging given the absence of robust immunohistochemical and molecular signatures. SOX11 expression has previously been shown to be present in a small subset of MPNST. In the present study, we evaluated a group of MPNST for SOX11 expression by immunohistochemistry. We similarly assessed a group of benign and malignant spindle cell tumors that are in the differential diagnosis of MPNST, to more expansively establish the specificity of the antibody. In total, 59 MPNSTs, 27 synovial sarcomas, 19 leiomyosarcomas, 19 rhabdomyosarcomas, 19 solitary fibrous tumors, 4 clear cell sarcomas of soft tissue, 19 malignant melanomas, 22 schwannomas (11 classical, 11 cellular), 9 neurofibromas (4 plexiform, 2 atypical, and 3 classical) and 9 nodular fasciitis were included. SOX11 was strongly positive in 41 of 59 MPNSTs (67 %), 16 of 27 synovial sarcomas (59 %), 11 of 19 rhabdomyosarcomas (58 %), 1 of 4 clear cell sarcomas (25 %), and 5 of 9 nodular fasciitis (56 %). In contrast, neurofibromas(n=11)), schwannomas (n=22), leiomyosarcomas (n=22), and solitary fibrous tumors (n=19) were either negative or showed only weak and focal expression for SOX11. The sensitivity and specificity of strong SOX11 expression in differentiating MPNST from its mimickers were 70 % and 73 %, respectively. In conclusion, the diagnostic utility of SOX11 expression for MPNST is limited, but the absence of significant SOX11 expression in benign/atypical nerve sheath tumors is interesting and deserves further investigation.
Salivary gland-like low-grade clear cell carcinomas of the thoracic cavity: A clinical, immunohistochemical, and molecular analysis of three cases
Weissferdt A, Wenig B and Moran CA
Three cases of an unusual neoplasm with striking clear cell features resembling salivary gland origin of the thoracic cavity are presented. The patients were three men between the ages of 52 and 69 years (average: 60.5 years), who presented with non-specific symptoms, such as chest pain, cough, and dyspnea. Diagnostic imaging showed that two tumors were intrapulmonary neoplasms, one in right lower lobe and one in the left upper lobe, while the third tumor was located in the anterior mediastinum. Surgical resection was accomplished in all cases. Grossly, the tumors were described as light tan, soft and well-delineated. Necrosis and hemorrhage were not present. Histologically, the three tumors showed similar morphological features consisting of a neoplastic cellular proliferation arranged in small lobules and round glandular structures, some of which contained amorphous eosinophilic secretions. Individual tumor cells had abundant clear cytoplasm, round nuclei, and inconspicuous nucleoli. Cellular atypia was minimal and only scattered mitotic figures were present. Immunohistochemical studies showed that the tumor cells were positive for pancytokeratin and GATA-3, focally and weakly positive for DOG1 and TRPS1 while negative for numerous other epithelial and neuroendocrine markers. Molecular analysis showed negative results for EGFR, ROS1, or ALK mutation, MAML2 and EWSR1 rearrangement and ETV6::NTRK3 fusion, respectively. Clinical follow up showed that all patients were alive without tumor recurrence or metastasis. We believe that the histological features, immunohistochemical profile, and the results of the molecular analysis are supportive of a yet undescribed tumor entity, provisionally designated as salivary gland-like low-grade clear cell carcinomas.
Utility of the manual hematology cell counter for Ki-67 assessment in gastrointestinal and pancreatobiliary well-differentiated neuroendocrine tumors
Htoo A, Arker SH, George RS, Chung L and Chen A
In the World Health Organization (WHO) 5th edition, prognosis of gastrointestinal (GI) well-differentiated neuroendocrine tumors (WDNET) depends on proliferation rate, commonly assessed by ki-67 immunohistochemical stain. In daily practice, the gold standard for WHO grade assessment by ki-67 staining, printing a photo of a tumor hotspot, counting the number of ki-67-positive cells out of 500 tumor cells, and calculating a percentage, is time-consuming and many cases are eyeballed. This study investigates the utility of a common tool, the manual cell counter used in hematology smear cell counting, for GI WDNET ki-67 counting. Of 59 resections, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 23 (39 %), 14 (24 %) and 7 (12 %) cases, respectively. Of 37 biopsies, the number of cases with a WHO grade difference between gold standard print-and-count and the original report, eyeballing, and hematology counter method, was 10 (27 %), 12 (32 %) and 7 (19 %) cases, respectively. For resections, Chi square analysis comparing hematology counter method versus original report, where many cases were likely eyeballed, showed statistically significantly less cases with differing WHO grades from gold standard print-and-count for hematology counter-assessed cases (P = 0.0007), and the same Chi square analysis was marginally not significant (P = 0.09) for hematology counter versus eyeballing. Times taken to perform hematology counter method were statistically significantly lower than times taken for print-and-count. This study suggests the hematology cell counter could strike a reasonable balance between time and accuracy for WDNET resections.
Variability in primary thyroid lymphoma: A clinicopathological exploration of diffuse large B-cell, marginal zone, and follicular lymphoma
Harahap AS, Santoso I, Charles S, Ardhiawan AVH, Assadyk AH and Ham MF
Primary thyroid lymphoma (PTL) is a rare condition, posing significant diagnostic challenges due to limited incidence and data. However timely and accurate diagnosis is crucial for effective management. This study aims to analyze the clinicopathological features of PTL cases observed over 15 years at a tertiary national referral hospital. PTL cases from 2009 to 2023 at Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital archives were retrospectively analyzed, with an assessment of clinical data, histopathological, and immunohistochemistry analysis. Statistical analysis was conducted using Chi-Square and Kruskal Wallis. Women constituted the majority of cases (male-to-female ratio was 1: 2.6), with a median patient age of 55 years. Of the 40 identified PTL cases, only one was a T-cell lymphoma among the non-Hodgkin lymphomas (NHL). The NHL subtypes included diffuse large B-cell lymphoma (DLBCL [72.5 %]), marginal zone lymphoma (15.0 %), and follicular lymphoma (FL [10.0 %]). An enlarged neck mass (94.7 %) was the most frequent symptom, and 42.1 % had a history of Hashimoto's thyroiditis. The overall surviving proportion in the present study is 80.7 %, with the median survival duration of 14.5 months, ranging from 1 to 54 months. The longest duration of survival documented in FL case and the shortest in DLBCL case. Lymphoepithelial lesions could be found in all lymphoma types. The main diagnostic and treatment modality used was surgery. Prompt diagnosis and personalized treatment approaches are important to improve survival outcomes. PTL should be anticipated in middle-aged women with rapid enlarged neck mass and a history of Hashimoto's thyroiditis.
Clinicopathological features analysis of Paraganglioma of urinary bladder: A retrospective study
Li W, Wei W, Yuan L, Zhang Y and MinYi
Paraganglioma of urinary bladder (PUB) is a rare neuroendocrine neoplasm. This study is a retrospective analysis of clinicopathological features in 11 cases of PUB. The studied cohort included seven male and four female patients with a median age of 64 years (range 37-73 years). The maximum tumor diameter ranged from 1 to 4 cm (median: 2.5 cm). Macroscopically, most lesions appeared as smooth, polypoid intraluminal protrusions; one case exhibited a nodular mass extending into the outer bladder wall. Microscopic evaluation demonstrated tumor infiltration into the muscularis propria (6 cases) or both lamina propria and muscularis propria (5 cases). Tumor cells were arranged in nested (Zellballen) or organoid patterns. Tumor cells uniformly expressed CD56, synaptophysin, and chromogranin. The Ki-67 proliferation index was ≤8 % in 10 cases; one case with a 4 cm tumor demonstrated a higher Ki-67 index (20 %), correlating with infiltrative growth and increased mitotic activity. Among the 10 cases that were evaluated, 2 (20 %) showed a loss of SDHB expression; Eight (80 %) of 10 cases were GATA3-positive, and all cases were negative for OCT3/4. Nine (81.8 %) underwent transurethral resection of bladder tumor, and 2 (18.2 %) underwent partial cystectomy. Intraoperative blood pressure fluctuations were observed in 2 patients (18.2 %). The median follow-up time was 26 months (range 4-73 months); one patient experienced a recurrence of endometrial cancer 4 years later and was lost to follow-up at 73 months; the remaining 10 patients survived without recurrence or metastasis. Improved preoperative recognition of PUBs relies on integrating clinical, biochemical, and imaging findings. Standardized immunohistochemical panels may enhance diagnostic accuracy.
Utility and limitations of Merlin immunohistochemistry for mesothelioma diagnosis in tissue sections and cell blocks
Nabeshima K, Hamasaki M, Furukawa T, Matsumoto S, Takizawa K, Adachi M and Goto Y
Distinguishing pleural mesothelioma (PM) from reactive mesothelial proliferations (RMP) can be challenging. In such cases, immunohistochemistry (IHC)-detected BAP1 or MTAP loss and FISH-detected CDKN2A homozygous deletion are effective. Merlin is the protein product of the NF2 gene, which is frequently altered in mesotheliomas. Recently, IHC-detected loss of Merlin was also shown to be useful in differentiating PM from RMP. To validate these findings, we examined Merlin IHC in PM cases, including for the first time cytologic material. Merlin IHC was performed on 67 PM cases, including 47 samples from tissues and 20 from cell blocks (CBs), and 29 RMP cases. In RMP, Merlin was expressed in cell membranes and cytoplasm, with no loss. Merlin expression was lost in 49 % of PM tissues. In discriminating PM from RMP, addition of Merlin IHC to the combination of BAP1 and MTAP IHC increased sensitivity from 77 % to 95 %. However, Merlin expression could not be assessed in 8.5 % of tissues and 25 % of CBs. In CBs, Merlin loss could be assessed only in sheeted or clustered tumor cells, because PM cells could not be identified precisely in few scattered tumor cells. In cases where both tissue biopsy and CBs were available, results matched in only 50 % of cases, suggesting uneven occurrence of Merlin loss in PM tissues. Our observations support the effectiveness of Merlin IHC in differentiating PM from RMP. However, investigators should be familiar with potential challenges in interpreting Merlin IHC results, especially in CBs.
Application of an in situ hybridization method for fungal diagnosis in formalin-fixed, paraffin-embedded allergic fungal rhinosinusitis tissue
Ma D, Ding J, Zhang L and Piao Y
Allergic fungal rhinosinusitis (AFRS) is a chronic inflammatory disease of the sinuses that can involve serious late complications; thus, prompt diagnosis is essential to determine the appropriate treatment. The most important diagnostic element of AFRS is the detection of noninvasive fungi within eosinophilic mucin. However, the rarity of fungal hyphae in ARFS makes it difficult to specifically identify them using histochemical staining alone. In this study, we designed a new in situ fungal detection probe for the diagnosis of fungi in formalin-fixed, paraffin-embedded AFRS tissues. Tissue sections from 49 patients with confirmed (n = 40) or suspected (n = 9) AFRS were selected for testing. A newly designed broad-spectrum probe for in situ hybridization (ISH) was compared with an anti-Aspergillus antibody in immunohistochemistry (IHC) and staining with hematoxylin and eosin and periodic acid-Schiff (PAS) to detect fungi. Hematoxylin and eosin staining had a lower detection rate (30/40 samples) than the other three methods. PAS staining led to two false-positive results in the AFRS-confirmed group and two false-negative results in the AFRS-suspected group. ISH and IHC exhibited high concordance (ĸ = 0.716); however, there was a high degree of nonspecific immunoreactivity to the anti-Aspergillus polyclonal antibody in some samples. The fungal detection rate of ISH was 95 % (38/40), with no background or nonspecific reactivity. Our novel broad-spectrum ISH probe provides more specific identification of fungi than PAS and IHC staining, exhibits no background reactivity, and may represent an essential upgrade to the in situ diagnosis of AFRS.
Histopathological and prognostic variability of ampullary tumors: A comprehensive study on tumor location, histological subtypes, and survival outcomes
Ozyigit Buyuktalanci D, Gun E, Dilek ON and Dilek FH
Ampullary tumors present diagnostic challenges due to the complex anatomical and histological structure of the ampullary region. They can be classified into four types based on location: Periampullary-duodenal, intra-ampullary, ampullary-ductal, and ampullary-NOS (not otherwise specified). Periampullary-duodenal tumors are exophytic, ulcerovegetative, and often intestinal-type adenocarcinomas with frequent lymph node metastasis. Intra-ampullary tumors are polypoid and confined to the ampullary canal. Ampullary-ductal tumors exhibit sclerotic thickening in the bile or pancreatic duct and are typically pancreatobiliary-type adenocarcinomas. Ampullary-NOS includes tumors that do not fit other classifications. This study aimed to classify ampullary tumors by their anatomical localization, compare histopathological features, and assess the prognostic outcomes for each group. A total of 111 ampullary tumors were selected from 229 pancreaticoduodenectomy specimens over 10 years at our hospital. Clinical, imaging, and macroscopic findings were re-evaluated microscopically. Tumors were classified into four anatomical groups, and their histopathological characteristics and prognosis were analyzed. The cohort had a mean age of 62 ± 10.49 years, with 69 (62.2 %) males and 42 (37.8 %) females. The median survival was 28.23 months. Tumor distribution was as follows: 14.4 % intra-ampullary, 25.2 % ampullary-ductal, 10.8 % periampullary-duodenal, and 49.5 % not otherwise specified (NOS). Pancreatobiliary-type adenocarcinoma (p = 0.003), perineural invasion (p < 0.0001), and lymphovascular invasion (p = 0.002) were significantly more frequent in the ampullary-ductal and NOS groups, which were associated with poorer overall survival (p = 0.011). In addition, lymphovascular invasion and surgical margin positivity were identified as independent prognostic markers. Classifying ampullary tumors based on anatomical location is crucial due to significant histopathological and prognostic differences between the groups.
Prognostic and clinicopathological significance of the new grading system for invasive pulmonary adenocarcinoma: A systematic review and meta-analysis
Guo W, Ruan H, Zhou M, Lei S and Li J
In 2020, the International Association for the Study of Lung Cancer (IASLC) introduced a new grading system for invasive pulmonary adenocarcinoma (IPA). This meta-analysis aimed to validate the prognostic utility of this grading system and identify relevant clinicopathological features. The PubMed, Embase, Web of Science, and Cochrane Library databases were searched for relevant studies published between January 1, 2020 and March 5, 2024. Hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were pooled to evaluate the effect of IASLC grading on prognosis. Odds ratios with corresponding 95 % CIs were pooled to assess relevant clinicopathological features. Twenty-two studies comprising 12,515 patients with IPA were included. Regarding overall survival, grade 3 adenocarcinomas had a worse prognosis compared with grades 1-2 (HR: 2.26, 95 % CI: 1.79-2.85, P<0.001), grade 1 (HR: 4.75, 95 % CI: 2.61-8.66, P<0.001), or grade 2 (HR: 1.71, 95 % CI: 1.28-2.29, P<0.001). Considering recurrence-free survival, grade 3 tumors had a higher recurrence risk than grades 1-2 (HR: 1.92, 95 % CI: 1.53-2.41, P<0.001), grade 1 (HR: 4.43, 95 % CI: 2.91-6.73, P<0.001), or grade 2 (HR: 1.67, 95 % CI: 1.33-2.10, P<0.001). In the subgroup analysis of stage I patients, grade 3 tumors exhibited a similarly poor prognosis. In addition, grade 3 adenocarcinomas were associated with aggressive clinicopathological features. This study demonstrated that the IASLC grading system is a robust predictor of prognostic stratification in patients with IPA, and warrants further promotion and worldwide implementation.
Clinicopathologic features of 6 cases of segmental atrophy of liver and review of the literature
Hu S, Zuo D and Meng L
Segmental atrophy (SA) of the liver is a rare and frequently under-recognized condition that can lead to the formation of pseudotumors, posing significant challenges in both clinical and imaging diagnoses. To date, this disease has been infrequently reported in the literature. To elucidate the clinicopathological characteristics of SA and enhance clinicians' understanding, we collected clinical and pathological data from 6 cases of SA and summarized the clinical information and pathological features of 22 previously reported SA patients. Among all cases, 19 patients were female and 9 were male, with a median age of 60 years. Lesion sizes varied widely, ranging from 1.5 to 10.5 cm. 17 patients exhibited notable right upper quadrant abdominal pain. Histological examination revealed a sequence of changes: early-stage lesions exhibited varying degrees of hepatic parenchyma collapse, brisk bile ductular proliferation, and extensive infiltration of chronic inflammatory cells, accompanied by very mild elastosis. In subsequent stages, the lesions exhibited reduced bile duct proliferation and inflammatory response alongside a notable increase in elastic fibers. Advanced-stage lesions presented with extensive elastic fiber deposition, occasionally interspersed with scattered islands of hepatocytes, and the terminal phase manifested as dense fibrotic nodules. Abnormally thick-walled blood vessels were identified in nearly all cases (n = 25), and bile duct cysts were observed in some cases (n = 11). In summary, SA primarily affects middle-aged individuals, with a female predominance, and presents with nonspecific clinical symptoms, predominantly right upper quadrant pain. Pathologically, it displays a continuous histomorphological spectrum. Elastic fiber staining has proven beneficial for both diagnosis and differential diagnosis of this condition. Proficiency in recognizing its diverse morphological features is essential for accurate diagnosis.