Diagnostic Pathology

Integrative prognostic model incorporating high mobility group box 1 subcellular localization and tumor-infiltrating lymphocytes in early-stage lung adenocarcinoma
Liu Y, Shimasaki M, Kumagai M, Han J, Shioya A, Sakurai M, Uramoto H and Yamada S
The prognostic impact of high mobility group box 1 (HMGB1) in lung adenocarcinoma may depend on its subcellular localization, while the density of tumor-infiltrating lymphocytes (TILs) reflects the host anti-tumor immune response. However, the combined prognostic value of these two factors in early-stage lung adenocarcinoma remains unclear.
Usefulness of BRG1 immunostaining in detecting SMARCA4 deficiency in "so-called" cancers of unknown primary in daily pathology practice
Hasegawa C, Washimi K, Hiroshima Y, Takahashi H, Sato S, Yoshioka E, Okubo Y and Miyagi Y
Integrated in-silico and in-vitro analysis of lncRNA H19/miRNA-675/p53 in OSCC: Structural characterization and molecular docking insights
Sekar R, Jayaraman S, Veeraraghavan V, Varadarajan S, Alagumuthu M, Rajendran P and Venkatesalu B
Long non-coding RNAs (lncRNA) H19 has drawn special attention because of its varied role in several malignancies, including OSCC. Therefore, this study was conducted to assess the association between H19-miR675-p53 by in-silico analysis, quantify the expression levels of H19, miRNA-675, and target oncogene p53 in cancerous versus normal individuals, and Correlate the Clinicopathological findings with their expression pattern.
High-grade uterine endometrial stromal sarcoma harboring GLI1 and MDM2/CDK4 co-amplifications
Zhang L, Luan L, Zhang L, Huang Y, Gu W, Yu S, Shen L, Huang J, Shao Y, Su J, Hou Y and Xu C
GLI1 gene alterations including fusions and amplifications compromise a subset of malignant mesenchymal tumors exhibiting characteristic monomorphic nested morphology and frequent S100 positivity, which mimic glomus tumors or well differentiated neuroendocrine tumors. We report four high-grade uterine endometrial stromal sarcomas (ESS) harboring GLI1 and MDM2/CDK4 co-amplifications with a median age of 51.5 years (range 43 ~ 72 years). Histologically, tumors showed a heterogenous morphology, including ovoid to spindle cells, showing nested/nodular arrangement (4/4). Myxoid background was observed at least partially in 4 tumors with prominent capillary networks. Mitoses index was 2 to 20/10 HPF (median 9.5/10 HPF). Immunochemically, tumors showed diffuse staining of CD10 (3/4) with frequently positive CyclinD1(2/4 tested) and mostly negative S100 protein (3/4). Next-generationsequencing (NGS) studies revealed GLI1 and MDM2/CDK4 co-amplification in all cases (4/4) and GLI1 fusion in 1 case (1/4), which were validated by fluorescence in situ hybridization (FISH) analysis. BCOR fusions were firstly identified with GLI1 and MDM2/CDK4 co-amplification in 2 cases (2/4). Copy number (CN) segmentation data showed GLI1 co-amplified cases present generally a single peak at the 12q13.3-15 locus. Follow-up (range:3 to 112 months; median 37.5 months) showed recurrence and/or metastasis in all cases (4/4), in which 1 patient developed lungs and liver metastasis. Relapse-free survival (RFS) analysis showed similar median RFS between GLI1 co-amplified HGESS and GLI1 non-amplified HGESS groups, which were shorter than LGESS group. Unusual clinicopathologic features of these HGESS with GLI1 and MDM2/CDK4 co-amplification mimicked other neoplasms, which caused significant diagnostic challenge and pitfalls. However, identification of GLI1 alterations in these tumors is beneficial for diagnosis and potential use of targeted GLI1 inhibitors.
Histopathological profile of endometrium among peri and post-menopausal women with abnormal uterine bleeding and its correlation with endometrial thickness by transvaginal sonography: a retrospective study
S V and Kudva R
Abnormal uterine bleeding (AUB) is a prevalent clinical concern, particularly in women approaching or beyond menopause. With a myriad of possible etiologies ranging from benign hyperplasia to malignant transformations, accurate diagnosis becomes crucial. This study aims to examine the histopathological patterns of the endometrium in peri- and postmenopausal women presenting with abnormal uterine bleeding and correlate these findings with endometrial thickness (ET) measured by transvaginal sonography (TVS).
Molecular abnormalities and clinical features in adult patients with acute myeloid leukemia in Thailand
Chantrathammachart P, Jinawath A, Puavilai T, Arsa L, Police P, Noikongdee P, Phojanasenee T, Sae-Lim P, Piyajaroenkij T, Choksomnuk P, Chuncharunee S and Niparuck P
The genetic heterogeneity observed in acute myeloid leukemia (AML) contributes to a wide range of clinical presentations and prognoses. We conducted a retrospective study to investigate genetic abnormalities, clinical characteristics, and survival of AML patients.
Prognostic utility of macrophage polarization (CD68/CD163 ratio) in Egyptian JAK2 positive myeloproliferative neoplasm patients: a single center study
Mahgoub SMA, Yehia MSM and Arafat AMA
Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders with variable clinical outcomes influenced by the bone marrow microenvironment. Tumor-associated macrophages (TAMs), particularly the M1 (CD68⁺) and M2 (CD163⁺) subtypes, play critical roles in inflammation, fibrosis, and immune modulation. This study evaluates CD68- and CD163-positive macrophage frequencies across MPN subtypes and their clinical/prognostic significance.
Prognostic value of manual and digital PD-L1 expression in pT3 and pT4 colon cancer
Jepsen DNM, Jensen MB, Bennedsen ALB, Grantzau TL, Eriksen TT, Eriksen JO, Bzorek M, Gögenur I and Fiehn AK
Programmed death ligand 1 (PD-L1) is a prognostic marker in several malignancies, but the prognostic value of PD-L1 expression in colorectal cancer (CRC) is inconclusive. Lack of standardized scoring systems for PD-L1 evaluation in CRC has led to inconsistent findings. This exploratory study aimed to evaluate PD-L1 expression using manual and digital methods and correlate the results to overall survival (OS) in a cohort of patients with pT3 and pT4 colon cancer (CC).
Utility of optimal proportion of tumor-infiltrating lymphocytes as a prognostic prediction of clinical outcome in intrahepatic cholangiocarcinoma: a single institution retrospective analysis
Kunprom W, Poonsiri N, Intarawichian P, Sa-Ngiamwibool P, Sangkhamanon S, Thanee M, Loilome W, Titapun A, Jareanrat A, Thanasukarn V, Srisuk T, Luvira V, Eurboonyanun K, Promsorn J, Koonmee S, Prajumwongs P and Aphivatanasiri C
Intrahepatic cholangiocarcinoma (iCCA), prevalent in Northeastern Thailand, presents challenges due to late diagnosis and metastasis. Prognostic factors are crucial. Tumor-infiltrating lymphocytes (TILs) hold promise as prognostic indicators and for immunotherapy, but their optimal proportion in iCCA prognosis is yet to be determined. We propose to evaluate the optimal proportion of TILs for predicting the outcomes of iCCA.
ANGPTL4 overexpression is associated with progression and poor prognoses of olfactory neuroblastoma
Yunyun Y, Yahui L and Yingshi P
To analyze expression levels of angiopoietin‑like 4 (ANGPTL4) in olfactory neuroblastoma (ONB) to investigate the association between ANGPTL4 and ONB.
SMARCB1 (INI-1) deficient vulvar neoplasms: report of 4 cases with review of literature
Kamboj M, Chadha P, Sharma A, Gupta S, Jain V, Bansal D, Pasricha S, Gupta G, Durga G and Mehta A
SMARCB1 (INI-1) deficient vulvar neoplasms are rare tumors with scarce available literature. These tumors can be comprised of proximal type epithelioid sarcoma (ES), myoepithelial carcinoma (MEC), myoepithelioma-like tumor of the vulvar region (MELTVR), and myxoepithelioid tumor with chordoid features (METC). A subset of vulvar yolk sac tumors (VYSTs) also exhibit INI-1 deficiency. Unlike other vulvar germ cell tumors, some researchers speculate these to be of non-germ cell origin. Herein, we report a spectrum of INI-1 deficient vulvar tumors comprising VYST (1 case), ES (1 case) and MELTVR (2 cases) which showed variable histomorphological features and concomitant lack of INI-1 expression on immunohistochemistry. The clinical course ranges from indolent to aggressive and all tumors warrant close clinical follow up. Management includes surgical excision with or without adjuvant therapy. Recognition of these unique neoplasms can aid in refining the classification scheme for such uncommon vulvar tumors.
Aberrant TTF-1 expression in metastatic colorectal adenocarcinoma mimicking primary lung cancer: a case report and review of diagnostic pitfalls
Tran NT, Van Thai N, Khuyen NT, Le LT and Khoa LTA
A 43-year-old man with sigmoid colon adenocarcinoma (low-grade, moderately) developed multiple pulmonary metastases, presenting an unusual immunohistochemical profile. Histologically, resected lung nodules showed metastatic adenocarcinoma consistent with colorectal origin, yet the tumor cells paradoxically expressed thyroid transcription factor-1 (TTF-1) - a marker typically specific to primary lung adenocarcinoma. Immunophenotyping demonstrated TTF-1 nuclear positivity in the metastatic tumor alongside a classic colorectal profile: cytokeratin 7 (CK7) negativity, cytokeratin 20 (CK20) positivity, strong caudal-type homeobox transcription factor 2 (CDX2) and special AT-rich sequence-binding protein 2 (SATB2) nuclear expression, and absence of Napsin A. The patient underwent surgical resection of the primary sigmoid colon tumor and received 16 cycles of capecitabine plus bevacizumab chemotherapy. Molecular testing revealed a KRAS c.35G > T (p.G12V) mutation in the tumor. This case highlights a potential diagnostic pitfall in metastatic colorectal cancer: aberrant TTF-1 expression can mimic a primary lung tumor. We discuss how the comprehensive immunohistochemical panel and genetic findings confirmed the colorectal origin of the lung lesions, emphasizing that combined marker profiles (TTF-1 +/CK7 -/CK20 +/CDX2 +/SATB2 +/Napsin A -) are more consistent with metastatic colorectal adenocarcinoma rather than an enteric-type adenocarcinoma of the lung, primary. The report reviews relevant literature and underscores the importance of correlating clinical history with pathology to avoid misdiagnosis.
Diagnostic value of AHNAK2 immunohistochemical expression in papillary thyroid carcinoma: an immunohistochemical study
Zhang X, Chen L, Deng M, Liang H, Jiang D, Wang H, Liu Y, Zhang R, Xu L, Liu J, Sujie A, Xu C, Liu Y and Hou Y
Multiple immunohistochemical markers including galectin-3 and BRAF V600E have been used to identify benign and malignant thyroid tumors. AHNAK nucleoprotein 2 (AHNAK2) is a novel oncogene that belongs to the AHNAK protein family and is upregulated in many malignant tumors, including thyroid cancers. However, its actual value in pathological diagnosis remains unknown. Therefore, we utilized a set of well-studied markers to further confirm the diagnostic role of AHNAK2 in differentiating thyroid tumors. Two hundred ninety-six papillary thyroid carcinomas (PTCs), 167 follicular adenomas (FAs), 36 follicular thyroid carcinomas (FTCs), and 11 non-invasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTPs) were collected. Markers including AHNAK2, galectin-3, BRAF V600E, HBME-1, Thyroid Peroxidase (TPO), CD56, and cyclin-D1 were used simultaneously for immunohistochemistry (IHC). The positivity rates of the PTC markers were as follows: AHNAK2 (95%), galectin-3 (89.5%), BRAF V600E (82.4%), HBME-1 (84.1%) CK19 (99.7%), cyclin-D1 (98.0%), TPO (61.1%), and CD56 (47.3%). AHNAK2 (4.2%), galectin-3 (6.0%), BRAF V600E (0.0%), HBME-1 (16.8%); CK19 (88.6%), cyclin-D1 (78.4%), TPO (94.0%), and CD56 (94.6%) were identified in FA. The areas under the receiver operating characteristic (ROC) curves for each marker in distinguishing PTCs from FAs were AHNAK2 (0.964), galectin-3 (0.935), BRAF V600E (0.907), HBME-1 (0.882), cyclin-D1 (0.776), CK19 (0.752), CD56 (0.053), TPO (0.004), and AHNAK2 in combination with galectin-3 and BRAF V600E (0.992). We firstly found that AHNAK2 was highly expressed in PTC and could be a new promising diagnostic marker for distinguishing thyroid tumors. The combination of AHNAK2 with galectin-3 and BRAF V600E can serve as an efficient diagnostic IHC panel for thyroid cancer, with great clinical potential.
Clinical significance of quantification of perineural cancer invasion on MRI-targeted prostate biopsy
Ramineni M, Wang Y and Miyamoto H
MRI-targeted biopsy (T-Bx) has considerably improved the detection of clinically significant prostate cancer, while the clinical impact of perineural invasion (PNI) seen on T-Bx remains unclear. We aimed to determine the prognostic significance of PNI quantification on T-Bx.
Metastatic endometrial stromal sarcoma with sex cord and neuroendocrine differentiation harboring a complex gene fusion
Sibira R, Cooke K, Shah A, Li X, Sen S, Varghese L and Klein M
Low-grade endometrial stromal sarcoma (LGESS) is a malignant stromal tumor characterized by an indolent clinical course, often with late recurrence or distant metastasis after a prolonged period of remission. These tumors can exhibit various lineage differentiations, making diagnosis challenging, especially in cases of remote recurrence. Most of these tumors are driven by fusions involving the JAZF1, SUZ12, and/or PHF1 genes.
EWSR1::BEND2 fusion sarcoma of the urinary bladder - a case report and review of literature
Halava V, Tuominen J, Lindholm P, Kyyrönen T, Kallajoki M and Orte K
In this case report we describe a Ewing-like high grade small round cell sarcoma of the urinary bladder in which an extremely rare EWSR1::BEND2 fusion was found. A 28-year-old male patient presented with hematuria and in the following examinations a large necrotic bladder tumor with spreading to adjacent prostatic tissue and multiple lung metastases were found. Histology showed a poorly differentiated small round cell tumor with perivascular rosettes and moderate membranous positivity for CD99. The methylation profile of the tumor did not match with any of the tumor entities grouped by the sarcoma classifier. With tumor agnostic methods, mainly next generation sequencing, novel fusions are being found at an accelerating rate. Our case adds to the expanding group of EWSR1 fusion neoplasms, and describes the effects of a Ewing sarcoma treatment protocol on this type of sarcoma. The relevance of traditional methods for detecting Ewing sarcoma with fluorescence in situ hybridization is decreasing as EWSR1 rearrangements are detected in tumors that show different clinical behavior and morphology. The classification of these tumors into WHO defined entities to guide treatment is a challenge.
Clinical significance and expression of ALDH1 in triple-negative breast cancer
Yang Y, Li Z, Zhu Y, Guo C, Yang L and Zhang J
Triple-negative breast cancer (TNBC) is aggressive and has limited therapeutic options due to the absence of targeted therapies, highlighting the urgent need for prognostic biomarkers linked to cancer stemness and chemoresistance. Aldehyde dehydrogenase 1 (ALDH1), a key regulator of stem cell properties, remains incompletely characterized in TNBC clinical cohorts.
Invasive breast carcinoma in a patient with PHTS: a case report
Zhan H, Fischbach N, Lynch M, Liang Y, Krishnamurti U and Cohen P
PTEN hamartoma tumor syndrome (PHTS) is a rare, multisystem disorder caused by germline pathogenic variants in the PTEN gene, predisposing individuals to various malignancies, including breast cancer.
Fine-needle aspiration cytology for the diagnosis of ewing's sarcoma in bone: a case report
Cai Y, Gu J, Wei X, Wang J, Fang J, Zhang H, Lv K, Meng Z and Liang Z
Ewing's sarcoma (ES) is an aggressive small round cell tumor traditionally diagnosed through open biopsy. We present a systematically evaluated case suggesting that standardized ultrasound-guided fine-needle aspiration cytology (FNAC), when combined with immunohistochemical (IHC) and molecular analysis, may provide diagnostic reliability approaching that of open biopsy. A 26-year-old female presented with an insidiously developing left popliteal fossa mass. Ultrasound-guided FNAC demonstrated characteristic small round blue cells, with IHC showing diffuse positivity for CD99, FLI-1, and Bcl-2. Subsequent fluorescence in situ hybridization (FISH) analysis identified the EWSR1 gene rearrangement. The patient exhibited significant radiographic response to neoadjuvant chemotherapy after two cycles, as evidenced by MRI. Definitive surgical resection specimens similarly demonstrated EWSR1 rearrangement by FISH, corroborating the initial diagnosis. Following four adjuvant chemotherapy cycles, the patient achieved disease-free status at the last follow-up. This case highlights the potential utility of optimized FNAC specimen triage (incorporating smears, liquid-based cytology, and cell blocks) for rare tumors, enabling comprehensive ancillary testing while maintaining diagnostic accuracy and supporting timely therapeutic decision-making.
Inflammatory fibroid polyps of the colon: a study on the morphological spectrum, immunoexpression characteristics, and outcomes
Changfei Q, Tingzhen Z, Xiangling L, Dingzhun L and Zhang W
Colonic inflammatory fibroid polyps (IFPs) have not been extensively studied.
Two unusual cases of tongue schwannoma with self-injurious factors: case reports and systemic literature review
Du G, Zhang J, Chen X, Lu R, Zhang J, Schmidt E and Zhou G
We present two cases of tongue schwannoma in two young males. The unusual, exogenetic clinical manifestation might be a big challenge for most dentists in making a correct diagnosis. The two patients had no special genetic or environmental background. Both patients denied cigarette smoking or alcohol abuse. Physical examination of the cervical lymph nodes yielded negative results. Their astonishing medical histories revealed that both had self-injurious practices using sharp instruments. The diagnosis of tongue schwannoma was confirmed by histopathology, revealing typical Antoni type A and B areas, and reactivity with S-100 by immunohistochemistry. The lesions were excised transorally under local anesthesia with no signs of recurrence for more than two years.