Diagn Pathol [JOURNAL]
Sun
200 papers
Mixed epithelial and stromal tumor of the seminal vesicles: report of a rare case with diagnostic, therapeutic, and prognostic insights.
Saeed F, Osunkoya AO
Diagn Pathol · 2025 Jun · PMID 40542384 · Full text
BACKGROUND: Mixed epithelial and stromal tumors (MESTs) of the seminal vesicle are exceptionally rare neoplasms composed of both epithelial and stromal elements, posing significant diagnostic challenges due to their rari...
BACKGROUND: Mixed epithelial and stromal tumors (MESTs) of the seminal vesicle are exceptionally rare neoplasms composed of both epithelial and stromal elements, posing significant diagnostic challenges due to their rarity and overlapping characteristics with other pelvic neoplasms. CASE PRESENTATION: We describe a 45-year-old patient with chronic pelvic pain and obstructive urinary symptoms. Imaging revealed a large cystic and solid mass involving his seminal vesicles, with significant mass effect on adjacent structures. Differential diagnoses included seminal vesicle adenocarcinoma and sarcoma. Complete surgical resection and subsequent histopathological analysis confirmed a low-grade seminal vesicle MEST with biphasic epithelial and stromal components, lacking atypia or notable mitotic activity. Immunohistochemical analysis revealed stromal positivity for estrogen receptor (ER), progesterone receptor (PR), smooth muscle actin, desmin, and CD34, and epithelial positivity for PAX8, PAX2, CK7, and MUC-6, supporting the diagnosis. The patient remains disease-free 32 months post-surgery. CONCLUSION: Seminal vesicle MESTs are rare and histologically diverse tumors, with pathogenesis likely hormonally influenced given ER and PR expression. Diagnosis requires a multidisciplinary approach, including imaging, histopathology, and immunohistochemistry. Surgical excision is the preferred treatment, offering an excellent prognosis for low-grade cases. This case emphasizes the importance of detailed documentation to improve understanding and management of these rare tumors, and its prognosis.
Bilateral synchronous salivary gland tumors: report of three cases.
van der Wal JE, Magan MB, Flygare L … +1 more , Nylander K
Diagn Pathol · 2025 Jun · PMID 40514698 · Full text
BACKGROUND: Bilateral salivary gland tumors, both benign and malignant and synchronous or metachronous are very rare. CASE PRESENTATION: Here three cases of synchronous bilateral salivary gland tumors are described and d...
BACKGROUND: Bilateral salivary gland tumors, both benign and malignant and synchronous or metachronous are very rare. CASE PRESENTATION: Here three cases of synchronous bilateral salivary gland tumors are described and discussed. Recognizing the entity is important for diagnostics and treatment planning. The first patient was a 56-year-old female with a bilateral parotid tumor, a malignant tumor, salivary duct carcinoma on the right side and a benign tumor, pleomorphic adenoma on the left side. The second patient was a 50-year old female with a bilateral benign parotid tumor, a pleomorphic adenoma. The third patient was a 51-year old female with a bilateral malignant tumor, an acinic cell carcinoma. Details on the diagnostic work-up, histopathology and treatment are described and discussed. CONCLUSIONS: In the case of a unilateral salivary gland tumor, especially of the major glands, the contralateral gland is always included in the clinical and radiological (MRI) head and neck evaluation prior to surgery, to detect or exclude possible bilateral occurrence.
Clinical pathological and molecular features of 100 patients with gastric-type cervical adenocarcinoma.
Gao S, Song Y
Diagn Pathol · 2025 Jun · PMID 40495175 · Full text
OBJECTIVE: To investigate the clinicopathological and molecular features, diagnosis, and differential diagnosis of gastric-type cervical adenocarcinoma (GAS). METHODS: A retrospective analysis was conducted on 100 patien...
OBJECTIVE: To investigate the clinicopathological and molecular features, diagnosis, and differential diagnosis of gastric-type cervical adenocarcinoma (GAS). METHODS: A retrospective analysis was conducted on 100 patients diagnosed with GAS at the National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, from January 2017 to January 2025. Clinicopathological data, histological characteristics, and immunohistochemical expression patterns were analyzed. Targeted next-generation sequencing (NGS) was performed on 11 cases. RESULTS: The cohort comprised 100 GAS patients (median age 50 years). Common clinical manifestations included abnormal uterine bleeding and vaginal discharge, with a significant proportion presenting at advanced FIGO stages (II-IV). Histological features were characteristic, and immunohistochemistry, including markers like MUC6, p16, PAX8, and PAX2, was crucial for diagnosis and differential diagnosis. Molecular analysis of 11 cases revealed a distinct high-frequency somatic mutation profile, including TP53 (72.7%), KRAS (45.5%), SMAD4 (45.5%), CDKN2A (36.4%), PIK3CA (27.3%) and STK11 (18.2%). This profile showed molecular homology with pancreaticobiliary adenocarcinoma and was characterized by microsatellite stable (MSS) and low tumor mutational burden (TMB). Regarding molecular markers and prognosis, aberrant p53 expression was frequent (50%, 37/74) but showed no significant association with clinicopathological factors or survival outcomes (p > 0.05). In contrast, PD-L1 expression (CPS ≥ 1) was significantly associated with higher FIGO stage (p = 0.021) and shorter progression-free survival (PFS) (p = 0.046). CONCLUSIONS: GAS is a highly malignant, HPV-independent cervical adenocarcinoma characterized by atypical clinical symptoms and complex histology. This study, representing a large cohort from Northern China, provides comprehensive insights into its clinicopathological and molecular landscape. We characterized its unique molecular profile and, importantly, identified PD-L1 (CPS ≥ 1) as a potential prognostic marker associated with shorter PFS. These findings contribute to improving diagnosis, understanding biological behavior, and identifying potential therapeutic targets for this aggressive subtype.
Large atypical perilobular hemangioma in the breast: a potential misdiagnosis as angiosarcoma.
Wei Y, Li M, Li H … +2 more , Han A, Shi H
Diagn Pathol · 2025 Jun · PMID 40483434 · Full text
BACKGROUND: Atypical perilobular hemangioma (APH) of the breast is a rare type of tumor. This tumor is often small, measuring no more than 2 mm in diameter, difficult to detect or palpate, and has a good prognosis. CASE...
BACKGROUND: Atypical perilobular hemangioma (APH) of the breast is a rare type of tumor. This tumor is often small, measuring no more than 2 mm in diameter, difficult to detect or palpate, and has a good prognosis. CASE PRESENTATION: We report a unique case of APH in a 47-year-old female patient, which was 12 mm in diameter and characterized by tumor cell atypia. To date, six cases of APH have been reported in the literature, including the present case. The mean age of the APH patients was 49.5 years (range: 39-75 years). The majority of APHs (4/6) in the breast were initially diagnosed as angiosarcoma. The tumor in our study presented diagnostic challenges as an atypical APH due to its substantial size (12 mm), the presence of indistinct borders in certain regions, an extensive growth pattern, the hobnail appearance of endothelial cells, and the mitotic count. CONCLUSION: In this study, we present this case to help with proper diagnosis and treatment of the tumor, to emphasize additional characteristics of APH, to summarize the clinicopathological features of this tumor as documented in the literature, and to enhance the understanding of this tumor type, particularly the differentiation between APH and low-grade angiosarcoma. CLINICAL TRIAL NUMBER: Not applicable.
Heterochronic pelvic high-grade myxoinflammatory fibroblastic sarcoma and uterine endometroid carcinoma harboring common gene mutations: a rare case report with genomic analysis.
Higashi Y, Mizuno M, Kitazono I … +6 more , Akahane T, Tasaki T, Noguchi H, Hisaoka M, Kobayashi H, Tanimoto A
Diagn Pathol · 2025 Jun · PMID 40462124 · Full text
OBJECTIVE: This report presents a rare case involving an extreme epithelial-to-mesenchymal transition, in which a specific type of sarcoma developed heterochronically as a recurrence of endometrioid carcinoma. CASE PRESE...
OBJECTIVE: This report presents a rare case involving an extreme epithelial-to-mesenchymal transition, in which a specific type of sarcoma developed heterochronically as a recurrence of endometrioid carcinoma. CASE PRESENTATION: A female in her 50's presented with abnormal genital bleeding, and an endometrial biopsy revealed endometrioid carcinoma. Following the diagnosis of stage IA endometrioid carcinoma according to the 2008 classification system of the International Federation of Gynecology and Obstetrics, a robot-assisted simple hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node navigation surgery were performed. Six months postoperatively, a tumor mass developed in the pelvis. A transrectal needle biopsy revealed spindle cell proliferation, and pelvic tumor resection was conducted for diagnostic therapy. The patient received no adjuvant chemotherapy or radiotherapy after the second surgery and remained free of tumor recurrence for 8 months. The resected yellowish solid tumor mass, measuring 16 × 12 × 9 cm, exhibited hemorrhage, necrosis, and cystic degeneration and was composed of fascicular proliferation of spindle tumor cells showing nuclear pleomorphism and frequent mitotic figures within a myxoid and inflammatory stroma. No epithelial component or organoid patterns were observed. Immunohistochemically, the tumor cells were positive for factor XIIIa, CD10, and cyclin D1, but negative for keratins (AE1/AE3 and CAM5.2) and other specific markers, supporting a diagnosis of high-grade myxoinflammatory fibroblastic sarcoma (MIFS). CONCLUSION: Genomic analysis revealed identical mutations in PTEN, PIK3R1, CDKN2 A, and TP53 in both the primary uterine endometrioid carcinoma and heterochronic pelvic MIFS. An integrative approach involving histology, immunohistochemistry, and genomic analysis is critical for elucidating the pathogenesis of rare pelvic and uterine tumors.
High-accuracy prediction of mutations in nine genes in lung adenocarcinoma via two-stage multi-instance learning on large-scale whole-slide images.
Zhao L, Zhao N, Zhong R … +12 more , Niu Y, Chang Z, Su P, Wang Z, Cui L, Wang B, Chen H, Wang X, Kong X, Du B, Ren F, Zhong D
Diagn Pathol · 2025 Jun · PMID 40457363 · Full text
BACKGROUND: Lung cancer is widely recognized as a prevalent malignant neoplasm. Traditional genetic testing methods face limitations such as high costs and lengthy procedures. The prediction of clinically relevant geneti...
BACKGROUND: Lung cancer is widely recognized as a prevalent malignant neoplasm. Traditional genetic testing methods face limitations such as high costs and lengthy procedures. The prediction of clinically relevant genetic mutations via histopathological images could facilitate the expedited identification of genetic mutations in clinical settings. METHODS: We collected 2,221 slides from 1999 patients diagnosed with lung adenocarcinoma. The data include whole-slide images data as well as information on gene mutations in EGFR, KRAS, ALK, HER2, and other rare genes (ROS1, RET, BRAF, PIK3CA, NRAS), and related clinical information. The self-supervised model DINO and the two-stage multi-instance network GAMIL were employed to accurately identify mutation statuses in 9 genes linked to tumorigenesis and cancer progression. The comparison of model performance involves the utilization of various foundation model (UNI), classification models (CLAM and Inception v3), external datasets (TCGA and other medical institutions), and comparative analysis with human pathologists. RESULTS: Our approach outperforms the CLAM and inception v3 model, achieving AUC values ranging from 0.825 to 0.987 for predicting gene mutations. The AUC value on the external test data set is 0.516-0.843. Furthermore, when comparing EGFR gene mutation prediction between pathologists and the GAMIL model, GAMIL exhibited a significantly higher AUC value of 0.810, exceeding the average AUC value of 0.508 achieved by pathologists. CONCLUSION: The GAMIL models exhibit outstanding performance in delineating tumor regions in lung adenocarcinoma and in forecasting gene mutations. The utilization of these models presents substantial potential for markedly improving molecular testing efficiency and opening novel pathways for personalized treatment. TRIAL REGISTRATION: Not applicable.
Pedunculated focal nodular hyperplasia: a case report, case series, and in-depth surgical, radiological, and histological analysis of a rare phenomenon.
Strange T, Gosnell JM, Bhargava P … +3 more , Al Harbi A, Cicalese L, Stevenson HL
Diagn Pathol · 2025 May · PMID 40448211 · Full text
BACKGROUND: Focal nodular hyperplasia (FNH) is a benign hepatic lesion that rarely presents as an exophytic mass attached by a fibrous stalk (termed pedunculated FNH). This variation poses a challenge to clinicians, with...
BACKGROUND: Focal nodular hyperplasia (FNH) is a benign hepatic lesion that rarely presents as an exophytic mass attached by a fibrous stalk (termed pedunculated FNH). This variation poses a challenge to clinicians, with atypical symptoms and imaging. CASE PRESENTATION: We describe a 33-year-old female who underwent excision of a pedunculated FNH. On gross examination, the lesion was lobular and vascular with homogenous tan-brown surfaces. Histological examination showed loss of normal liver architecture, abnormal intervening fibrous tracts, dysplastic arteries, and focal steatosis. Immunohistochemical staining with glutamine synthetase resulted in a branching, or "map-like" pattern. These findings were consistent with focal nodular hyperplasia. One of the most sensitive imaging techniques for diagnosing this lesion involves magnetic resonance imaging (MRI) with contrast, which discloses a homogenous mass that is hyperintense during the arterial phase with gradual decrease in intensity during the venous and equilibrium phases. The central stellate scar will often remain hyperintense for a prolonged period of time. On histology, normal hepatic architecture is lost to abnormal fibrotic bands and a characteristic stellate scar. Immunohistochemistry with glutamine synthetase uniquely highlights a map-like pattern that is not seen in other liver lesions. CONCLUSIONS: Due to its atypical presentation and increased risk of complications compared to its intrahepatic counterpart, pedunculated FNH brings unique challenges for diagnosis and therapy. Proper identification of pedunculated FNH is critical for appropriate treatment. Our case highlights the importance of radiological and histopathological studies to accurately identify this lesion, as well as the benefits of surgical removal to prevent serious complications.
Mutational analysis and protein expression of PI3K/AKT pathway in four mucinous cystadenocarcinoma of the breast.
Zheng Y, Tang H, Liu Q … +4 more , Zhang Y, Zhao P, Zhang S, Wang C
Diagn Pathol · 2025 May · PMID 40437613 · Full text
INTRODUCTION: Primary mucinous cystadenocarcinoma of the breast (BMCA) is a rare neoplasm with few reports in the literature. Its molecular characteristics, prognosis, and treatment protocols are not well understood, and...
INTRODUCTION: Primary mucinous cystadenocarcinoma of the breast (BMCA) is a rare neoplasm with few reports in the literature. Its molecular characteristics, prognosis, and treatment protocols are not well understood, and there is a lack of consensus concerning the optimal management of this condition. METHODS: Four cases of clinical and pathological data were collected from 2018 to 2024. Next generation sequencing with a 654 cancer-associated gene panel was utilized to detect gene mutations. Immunohistochemistry was carried out to evaluate protein expression levels. RESULTS: Firstly, we combined clinical imaging examinations and IHC to exclude the possibility of metastasis from ovarian or pancreatic origins. BMCA was composed of cystically dilated ducts lined by tall columnar mucin-containing epithelium. The morphological spectrum of MCA varied from MCA alone to MCA combined with carcinoma in situ (CIS) to MCA associated with invasive ductal carcinoma (IDC). ER/PR/HER2 and CK20 were all negative, while CK7 and GATA3 were positive by IHC in four cases. Although the prognosis of the other three patients was favorable during the follow-up periods of 13, 10, and 3 months, respectively, case 2# experienced a recurrence of the primary focus after 42 months. No lymphatic metastasis was identified in cases 1-4#. In addition, next-generation sequencing (NGS) identified 17 mutated genes and 25 mutation sites in four cases. TP53, PIK3CA, AKT, PTEN, and RB1 were the highest frequency mutated genes. Given that AKT mutations typically refer to AKT1(E17K) rather than AKT2 or AKT3, AKT protein expression was detected only in Case 2# (AKT1, E17K). PTEN protein was expressed in case 4# (corresponded to missense mutation), loss of PTEN expression were corresponding with splicing mutation in case1#. In brief, AKT and PTEN protein expression could be corresponded to gene mutation in a certain extent. However, PIK3CA protein expression was positive in Case 2# but negative in Case 1#, which did not fully accordance with the NGS-detected missense mutations. No associated germline variations were detected. Additionally, neither PDL-1 expression nor microsatellite instability-high (MSI-H) status was identified. CONCLUSION: The tumorigenesis and development of BMCA may be regulated to the PI3K/AKT pathway. Consequently, a comprehensive genetic analysis of more cases could elucidate the molecular mechanisms underlying this rare tumor.
OCT4 and MENA immunoprofiling in salivary mucoepidermoid carcinoma.
Samir O, Farag DA, Ali KM … +1 more , Ismail LEM
Diagn Pathol · 2025 May · PMID 40426241 · Full text
BACKGROUND: Mucoepidermoid carcinoma (MEC) emblematizes the predominant malignant salivary gland neoplasm, characterized by its heterogeneous morphological features and diverse clinical representations. The expression pa...
BACKGROUND: Mucoepidermoid carcinoma (MEC) emblematizes the predominant malignant salivary gland neoplasm, characterized by its heterogeneous morphological features and diverse clinical representations. The expression patterns and prognostic significance of Octamer transcription factor 4 (OCT4) and Mammalian-enabled (MENA) protein in MEC perdure are incompletely described. METHODS: Immunohistochemical analysis was performed on 46 archival MEC specimens and 5 normal salivary-gland controls. OCT4 and MENA staining were assessed histomorphometrically and correlated with clinicopathological parameters. Statistical analysis comprised Monte Carlo and Spearman's correlation tests. RESULTS: OCT4 revealed selective cytoplasmic immunoreactivity in intermediate and epidermoid cells, without nuclear positivity. Strong OCT4 expression predominated in low-grade (66.7%), while high-grade MEC exhibited variable immunoreactivity, with 53% showing weak expression. No significant correlation was found between OCT4 expression and clinical or pathological data. MENA showed cytoplasmic and membranous immunolocalization, with expression patterns correlated significantly with age (p = 0.015), tumor size (p = 0.012), clinical stage (p = 0.004), and histological grading (p = 0.001). Spearman's correlation analysis revealed a weak, non-significant association between OCT4 and MENA expression (r = 0.05, p = 0.744). CONCLUSIONS: The differential expression patterns of OCT4 and MENA in MEC prognosticate distinct regulatory mechanisms. While OCT4 cytoplasmic expression may presage early involvement in carcinogenesis, MENA cellular expression portends potentially independent molecular pathways, possibly encompassing subnetworks in the Wnt/β-catenin and TGF-β signaling cascades. MENA may serve as a biomarker for predicting the aggressive behavior of MEC.
Human pegivirus detected in patient with reversible severe encephalitis and axillary lymphadenopathy: a case report.
He J, Yang L, Niu C
Diagn Pathol · 2025 May · PMID 40426166 · Full text
Human pegivirus (HPgV) has been postulated as a potential etiological factor in encephalomyelitis and exhibits lymphotropic characteristics. However, the co-occurrence of encephalitis and lymphadenopathy with HPgV detect...
Human pegivirus (HPgV) has been postulated as a potential etiological factor in encephalomyelitis and exhibits lymphotropic characteristics. However, the co-occurrence of encephalitis and lymphadenopathy with HPgV detected has never been reported. Herein, we report a case of a 48-year-old woman admitted with fever followed by sudden loss of consciousness. Radiological imaging demonstrated encephalitis and lymphadenopathy. Initial analysis of blood and cerebrospinal fluid (CSF) failed to reveal specific etiology. The only pathogen found in CSF was later determined to be HPgV using metagenomic next-generation sequencing (mNGS). After receiving treatment with acyclovir, meropenem, and ceftriaxone sodium, the patient fully recovered. This case contributes additional evidence in support of the hypothesis regarding the pathogenic potential of HPgV and highlights the diagnostic utility of mNGS in detecting rare pathogens.
Complex papillary hyperplasia of the endometrium: an uncommon case report with cytopathological features and diagnostic implications.
Wang R, Wu Y, Jia Z
Diagn Pathol · 2025 May · PMID 40420208 · Full text
BACKGROUND: Complex papillary hyperplasia of the endometrium (CPHE) is a rare benign lesion with overlapping features of malignancy, posing significant diagnostic challenges. This case highlights the importance of multid...
BACKGROUND: Complex papillary hyperplasia of the endometrium (CPHE) is a rare benign lesion with overlapping features of malignancy, posing significant diagnostic challenges. This case highlights the importance of multidisciplinary evaluation to avoid misdiagnosis and overtreatment. CASE PRESENTATION: A 49-year-old premenopausal woman presented with irregular vaginal bleeding. Histopathological examination revealed multifocal lesions confined within and on the surface of endometrial polyps, exhibiting complex papillary structures with bland cytology. Immunohistochemistry showed strong ER/PR positivity and retained PTEN expression, while molecular analysis confirmed the absence of high-risk mutations (PTEN, PIK3CA, TP53, CTNNB1). CONCLUSIONS: CPHE requires integration of histopathology, immunohistochemistry, and molecular diagnostics to distinguish it from malignancies. Conservative management is justified in molecularly confirmed cases.
Immunohistochemical profile of non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) versus other thyroid follicular lesions.
Samaka RM, Hemida AS, Alfouly H … +1 more , Kora MA
Diagn Pathol · 2025 May · PMID 40420140 · Full text
BACKGROUND: A follicular thyroid tumour called Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses crossing-over morphologic characteristics with more thyroid follicular lesions wh...
BACKGROUND: A follicular thyroid tumour called Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) poses crossing-over morphologic characteristics with more thyroid follicular lesions whether benign or cancerous nodules. This study focuses on analysing the expression of CD56, HBME-1, RRM2 and APLP2 IHC markers in NIFTP versus other thyroid follicular lesions and their diagnostic validity was also evaluated. METHODS: one hundred and nine thyroidectomy specimens including 31 NIFTP, 34 non-neoplastic, 34 papillary thyroid carcinoma (PTC) and 10 invasive encapsulated follicular variant papillary thyroid carcinoma (IEFVPTC) cases, were acquired between 2019 and 2022 from the Menoufia University's Faculty of Medicine's Pathology Department. Tissue microarray construction (TMA) blocks were prepared and CD56, HBME-1, RRM2 and APLP2 immunostaining were performed. RESULTS: For CD56, 64.5% of NIFTP, 97.1% of the non-neoplastic group and 0% of both PTC and IEFVPTC were positive. For HBME-1, 61.3% of NIFTP, 0% of non-neoplastic, 100% of PTC and 100% of IEFVPTC were positive. For RRM2, all cases of NIFTP and the non-neoplastic group were negative, 88.2% of PTC and 100.0% of IEFVPTC were positive. For APLP2, 90.3% of NIFTP, 100% of the non-neoplastic group, 100% of PTC and 100% of IEFVPTC were positive. In differentiating NIFTP from non-neoplastic cases, the most sensitive marker was CD56 at H-score < 225 (sensitivity 95%) and the most specific was HBME-1 (specificity 100%). In various combinations, the panel of combined HBME-1 with either CD56 or APLP-2 improves their specificity (96.67% and 100% respectively) and the diagnostic accuracy (86.79 and 83.87, respectively) and therefore, combined HBME-1 and CD56 seems to be the most significant than using a single marker. In differentiation between NIFTP and PTC/IEFVPTC, the most sensitive marker was RRM2 (100% sensitivity for both groups) with the highest diagnostic accuracy (93.85% and 100%, respectively) and the most specific was CD56 (specificity 100% for both groups). CONCLUSIONS: Immunohistochemical markers such as CD56, HBME-1, RRM2, and APLP2 may aid in the diagnosis of NIFTP and its distinction from other follicular lesions.
A locally aggressive pelvic MEIS1::NCOA1 fusion sarcoma in a young adult female: a case report and review of the literature.
Ramineni M, Armbuster YC, Katerji H … +3 more , Huang W, McDowell JL, Wang X
Diagn Pathol · 2025 May · PMID 40420135 · Full text
MEIS1::NCOA1/2 fusions have been identified in spindle cell tumors of the gynecologic and genitourinary tracts, as well as in two cases of intraosseous spindle cell rhabdomyosarcomas. These tumors typically exhibit an in...
MEIS1::NCOA1/2 fusions have been identified in spindle cell tumors of the gynecologic and genitourinary tracts, as well as in two cases of intraosseous spindle cell rhabdomyosarcomas. These tumors typically exhibit an infiltrative growth pattern characterized by short fascicles of monomorphic, plump spindle cells. Their immunoprofile is nonspecific, often demonstrating focal and variable expression of ER, PR, CD10, and cyclin D1. Depending on their location, these tumors are frequently diagnosed as low-grade endometrial stromal sarcomas or undifferentiated uterine or renal sarcomas. While they generally exhibit low malignant potential with multiple local recurrences, two cases with high-grade morphology and lung metastases have been reported. Here, we describe a case of pelvic low-grade spindle cell sarcoma in a 19-year-old woman characterized by strong diffuse ER/PR expression and focal CD10 positivity. Next-generation sequencing revealed a MEIS1::NCOA1 fusion without additional genetic alterations. She presented with extensive local disease throughout the abdomen, while the uterus and adnexa appeared normal intraoperatively.
"Colon"ised by the unexpected: a case of extrauterine epithelioid trophoblastic tumour.
Radhakrishnan S, Suvarna NN, Sreeram S … +1 more , Bhat S
Diagn Pathol · 2025 May · PMID 40413529 · Full text
INTRODUCTION: Extrauterine epithelioid trophoblastic tumour is an exceedingly rare and aggressive form of gestational trophoblastic disease that arises outside the uterus and is characterised by the proliferation of inte...
INTRODUCTION: Extrauterine epithelioid trophoblastic tumour is an exceedingly rare and aggressive form of gestational trophoblastic disease that arises outside the uterus and is characterised by the proliferation of intermediate trophoblastic cells. Unlike more common forms of gestational trophoblastic diseases, such as hydatidiform moles and choriocarcinoma, this entity presents unique diagnostic and therapeutic challenges due to its atypical location and clinical features. Thus far, no documented cases of this entity have been reported in the colon. CASE PRESENTATION: We report the case of a 42-year-old woman who presented with complaints of lower abdominal pain and a palpable mass in the left iliac fossa, initially suspected to be an ectopic pregnancy. On radiological evaluation, a provisional diagnosis of gastrointestinal stromal tumour was made, following which the patient underwent a left colectomy with resection and anastomosis, and the excised specimen on comprehensive histopathological and immunohistochemical analysis was diagnosed as a case of extrauterine epithelioid trophoblastic tumour. However, the patient's condition deteriorated, and she succumbed to the disease one month after the diagnosis. CONCLUSION: The rarity of extrauterine trophoblastic tumours contributes to limited clinical experience and treatment protocols, resulting in poor prognoses. This case report highlights the importance of histopathological examination for a confirmatory diagnosis, ensuring timely identification and improving patient outcomes.
A novel KRAS exon 2 drop-off digital PCR assay for mutation detection in cell-free DNA of cancer patients.
Addamo-De Nard B, Geissmann M, Akhoundova D … +6 more , Pistoni C, Brezina T, Zoche M, Weber A, Hussung S, Fritsch R
Diagn Pathol · 2025 May · PMID 40413426 · Full text
BACKGROUND: KRAS exon 2 mutations are highly prevalent in human malignancies, making them attractive targets for detection and monitoring in cell-free DNA (cfDNA) of cancer patients. Drop-off assays designed for digital...
BACKGROUND: KRAS exon 2 mutations are highly prevalent in human malignancies, making them attractive targets for detection and monitoring in cell-free DNA (cfDNA) of cancer patients. Drop-off assays designed for digital polymerase chain reaction (ddPCR drop-off) span entire mutational hotspots and detect any mutated allele within the covered region, overcoming a major limitation of mutation-specific ddPCR assays. We therefore set out to develop a novel KRAS codon 12/13 ddPCR drop-off assay for the robust, highly sensitive and specific detection of KRAS exon 2 hotspot mutations in cfDNA. METHODS: We designed, optimized and extensively validated a KRAS codon 12/13 ddPCR drop-off assay. We compared assay performance to a commercially available KRAS multiplex assay. For clinical validation, we analyzed plasma samples collected from patients with KRAS-mutated gastrointestinal malignancies. RESULTS: Limit of detection of the newly established ddPCR drop-off assay was 0.57 copies/µL, limit of blank was 0.13 copies/µ. The inter-assay precision (r) was 0.9096. Our newly developed KRAS ddPCR drop-off assay accurately identified single nucleotide variants in 35/36 (97.2%) of circulating tumor DNA-positive samples from the patient validation cohort. Assay cross-validation showed that the newly established KRAS codon 12/13 ddPCR drop-off assay outperformed a commercially available KRAS multiplex ddPCR assay in terms of specificity. Moreover, the newly developed assay proved to be suitable for multiplexing with mutation-specific probes. CONCLUSION: We developed and clinically validated a highly accurate ddPCR drop-off assay for KRAS exon 2 hot-spot detection in cfDNA with broad applicability for clinic and research.
A case report: iridociliary melanocytoma associated with secondary glaucoma.
Sun Y, Chen Y, Zhu J … +2 more , Guo J, Wang Z
Diagn Pathol · 2025 May · PMID 40375263 · Full text
BACKGROUND: Distinguishing between benign iridociliary melanocytoma and malignant melanoma presents a diagnostic challenge, particularly given the potential overlap in tumor growth patterns and clinical manifestations, e...
BACKGROUND: Distinguishing between benign iridociliary melanocytoma and malignant melanoma presents a diagnostic challenge, particularly given the potential overlap in tumor growth patterns and clinical manifestations, especially when patients present with secondary glaucoma. Misdiagnosis may induce severe clinical consequences, including enucleation. Therefore, the judicious selection of biopsy or surgical techniques is crucial in both diagnosing and managing the condition. CASE PRESENTATION: A 44-year-old female presented with uncontrolled elevated intraocular pressure (IOP) and a heavily pigmented iris lesion extending into the anterior chamber angle and adjacent ciliary body. Unexpectedly, standardized initial fine-needle aspiration biopsy (FNAB) yielded inconclusive results. Subsequent excisional surgery (partial iridocyclectomy and concurrent phacoemulsification) was performed to remove the tumor mass and treat cataract. Histopathological analysis confirmed the diagnosis as melanocytoma. Lens implantation followed upon normalization of IOP within 8 months. At the 2-year follow-up, the patient exhibited a satisfactory clinical outcome, with no tumor recurrence, achieving a best-corrected visual acuity of 20/40 and an intraocular pressure of 18.5 mmHg. CONCLUSIONS: This case underscores the importance of obtaining adequate tumor specimens for accurate diagnosis via FNAB in iris and ciliary body tumors. Additionally, for patients with secondary glaucoma, partial iridocyclectomy emerges as a promising intervention, addressing anterior chamber angle obstruction to alleviate IOP while facilitating histopathological diagnosis for subsequent management.
Long-chain fatty acyl CoA synthetase 4 expression in pancreatic cancer: a marker for malignant lesions and prognostic indicator for recurrence.
Uchihara D, Shimajiri S, Harada Y … +10 more , Kumamoto K, Oe S, Miyagawa K, Nakamura K, Katafuchi E, Nuratdinova F, Honma Y, Shibata M, Harada M, Nakayama T
Diagn Pathol · 2025 May · PMID 40349055 · Full text
BACKGROUND: Long-chain fatty acyl CoA synthetase 4 (ACSL4) is crucial for lipid metabolism, primarily catalyzing the formation of 12-20 carbon chain fatty acids. ACSL4 is upregulated in various cancers and linked to aggr...
BACKGROUND: Long-chain fatty acyl CoA synthetase 4 (ACSL4) is crucial for lipid metabolism, primarily catalyzing the formation of 12-20 carbon chain fatty acids. ACSL4 is upregulated in various cancers and linked to aggressive behavior and poor survival. A bioinformatics study showing ACSL4 upregulation in pancreatic cancer. However, utility for actual pathological diagnosis and clinical significance in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) are unexplored. This study aimed to investigate ACSL4 expression in PDAC and IPMN, and evaluate its clinical implications. METHODS: We examined ACSL4 expression using immunohistochemistry in 165 patients with PDAC and IPMN. Differences in ACSL4 expression between malignant and benign lesions were evaluated using the Pearson χ2 test. The association between ACSL4 expression, pathological parameters, and survival was assessed through Kaplan-Meier and Cox regression analyses in 96 patients with invasive cancer. RESULTS: Compared to normal pancreatic ducts, low-grade pancreatic intraepithelial neoplasm, and intraductal papillary mucinous adenoma (IPMA) (3.3%, 3.4%, and 2.7%, respectively), ACSL4 expression was significantly higher in invasive PDAC, noninvasive intraductal papillary mucinous carcinoma (IPMC), and invasive IPMC (77%, 86.7%, and 93.9%, respectively). In invasive cancers, low ACSL4 expression was associated with a higher frequency of lymphovascular invasion and recurrence and shorter disease-free survival (P = 0.006). Additionally, low ACSL4 expression was an independent prognostic factor for shorter disease-free survival in multivariable Cox regression analysis (HR = 2.409, 95% CI: 1.121-5.180, P = 0.024). CONCLUSION: ACSL4 expression helps differentiate cancerous from precancerous lesions in pancreatic cancer, but low expression is linked to a higher frequency of lymphovascular invasion and shorter disease-free survival in invasive cases. Due to the limited sample size and broad confidence intervals, the findings of this study should be interpreted with caution and require validation in larger, independent cohorts.
Retroperitoneal mucinous cystadenoma with neuroendocrine differentiation: a rare case and comprehensive approach to diagnosis and management.
Ho Y, Chen WY, Lai CH … +1 more , Syu SH
Diagn Pathol · 2025 May · PMID 40319316 · Full text
BACKGROUND: Retroperitoneal mucinous cystadenomas are exceptionally rare neoplasms, with limited cases reported in the literature. The occurrence of neuroendocrine differentiation in such tumors is even more uncommon, po...
BACKGROUND: Retroperitoneal mucinous cystadenomas are exceptionally rare neoplasms, with limited cases reported in the literature. The occurrence of neuroendocrine differentiation in such tumors is even more uncommon, posing unique diagnostic and management challenges. CASE PRESENTATION: We report a case of a 32-year-old woman who was incidentally diagnosed with a right retroperitoneal cyst during routine prenatal ultrasonography. The patient remained asymptomatic until postpartum, prompting further evaluation of the cyst. Imaging studies identified a large cystic mass, ultimately leading to diagnostic laparoscopy and surgical excision. Histopathological analysis confirmed the diagnosis of a mucinous cystadenoma with neuroendocrine cell proliferation. DISCUSSION: This case highlights the complexity of diagnosing and managing retroperitoneal mucinous cystadenomas, particularly those with neuroendocrine features. Given the rarity of these tumors, thorough histopathological examination is crucial to differentiate them from other cystic lesions. Surgical excision remains the definitive treatment, with long-term follow-up essential to ensure complete resolution and monitor for recurrence or malignant transformation. CONCLUSION: Retroperitoneal mucinous cystadenomas with neuroendocrine differentiation represent a rare clinical entity requiring careful evaluation. This report underscores the importance of considering neuroendocrine differentiation in retroperitoneal cystic lesions and emphasizes the role of complete surgical excision followed by close monitoring to ensure favorable outcomes.
CD200 in acute myeloid leukemia: marked upregulation in CEBPA biallelic mutated cases.
González-Guerrero L, Castellet H, Martínez C … +16 more , González N, Guijarro F, Lloveras N, Pratcorona M, Gich I, Berenguer-Molins P, Perera-Bel J, Zamora L, Mascaró M, Sampol A, Garcia-Guiñón A, Vives S, Tormo M, Arnan M, Villamor N, Nomdedéu JF
Diagn Pathol · 2025 Apr · PMID 40307896 · Full text
CD200 is a glycoprotein that binds with its receptor CD200R, providing immunosuppressive signals to T and NK cells. CD200 is expressed by normal stem cells and progenitors committed to B-lymphopoiesis and myeloid develop...
CD200 is a glycoprotein that binds with its receptor CD200R, providing immunosuppressive signals to T and NK cells. CD200 is expressed by normal stem cells and progenitors committed to B-lymphopoiesis and myeloid development. CD200 biological relevance in acute leukemias is only partially understood.The study included a consecutive series of four hundred thirty-one patients with acute myeloid leukemia (AML). Immunophenotype was established by multiparametric flow cytometry, and the genetic diagnosis was performed by PCR-based methods and a targeted resequencing method covering 42 genes.66% of AML patients expressed CD200 being significantly associated with CD34 reactivity. The frequency of CD200 positivity was higher in cases with core-binding factor genetic lesions such as RUNX1-RUNX1T1 (81.3%) fusions and CBFB-MHY11 (63.2%) rearrangements and also with biallelic CEBPA mutations (100%). The molecular AML group with the lowest CD200 reactivity (19.1%) corresponded to AML with NPM1 mutations. RNA seq showed no uniform pattern of infiltrating cells in CEBPA mutated AML. Deconvolution analysis may be used to assess the immunoregulatory mechanisms of AML.CD200 expression could help identify the more immature compartment and, combined with other markers, single out CEPA-mutated AML.
Diagnostic insights into solid pseudopapillary neoplasms of the pancreas: a decade of experience with pediatric representation.
Ebrahim NAA, Othman MO, Salama RA … +2 more , Abdelfatah D, Tahoun NS
Diagn Pathol · 2025 Apr · PMID 40307756 · Full text
BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade malignancies that predominantly affect young females. Their diagnosis is often facilitated by a characteristic histomorphological pat...
BACKGROUND: Solid pseudopapillary neoplasms (SPNs) of the pancreas are rare, low-grade malignancies that predominantly affect young females. Their diagnosis is often facilitated by a characteristic histomorphological pattern and immunohistochemical profile. However, diagnostic challenges persist, especially in pediatric and atypical presentations. Recent attention has focused on the diagnostic value of CD99 and LEF1 in distinguishing SPNs from other pancreatic neoplasms. OBJECTIVE: To evaluate the diagnostic accuracy and utility of CD99 and LEF1 as immunohistochemical markers for SPNs. METHODS: A retrospective analysis of 60 SPN cases diagnosed between 2015 and 2024 was performed. Histopathological features were systematically reviewed, and immunohistochemical staining for CD99, LEF1, β-catenin, Cyclin D1, PR, Ki-67 was evaluated. Immunohistochemical marker interpretation was standardized using internally validated thresholds informed by existing literature: CD99 was considered positive with ≥ 10% cytoplasmic staining exhibiting paranuclear accentuation; β-catenin positivity was defined by ≥ 5% nuclear localization; Cyclin D1 by ≥ 10% moderate-to-strong nuclear staining; and progesterone receptor (PR) expression by ≥ 1% nuclear positivity, consistent with hormone receptor evaluation guidelines. Marker expression was statistically analyzed for their associations. RESULTS: SPNs exhibited a strong female predilection (F:M ratio ≈ 7:1), with a mean age of 32.5 years. Pediatric cases (n = 4) displayed higher mean expression of CD99 (73.8%) and LEF1 (86.5%) compared to adults. CD99 showed cytoplasmic positivity with paranuclear accentuation in 96.7% of cases, while LEF1 demonstrated nuclear staining in 91.7%. β-catenin nuclear localization was observed in 95% of tumors, reflecting Wnt/β-catenin pathway activation. Cyclin D1 and PR were expressed in 90% and 88.3% of cases, respectively. Co-expression of β-catenin, CD99, LEF1, Cyclin D1, and PR was observed in 73.3% of tumors. CD99 and LEF1 inversely correlated with tumor size and proliferative activity (Ki-67), whereas Cyclin D1 and Ki-67 positively correlated with tumor size and lymphovascular invasion (LVI). Pediatric tumors generally exhibited favorable profiles, with limited evidence of LVI. CONCLUSION: SPNs present with distinctive immunohistochemical signatures that are critical for accurate diagnosis, particularly in morphologically ambiguous or pediatric cases. CD99 and LEF1 are highly sensitive markers that, in combination with β-catenin and Cyclin D1, enhance diagnostic precision. These findings emphasize the central role of Wnt/β-catenin signaling in SPN pathogenesis and underscore the importance of integrating clinicopathological and molecular data for comprehensive tumor assessment.
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