中华病理学杂志最新文献

Objective: To investigate the clinicopathological features and molecular genetics of large B-cell lymphoma with IRF4 gene rearrangements (LBL-IRF4) involving the head and neck region in adults. Methods: The clinicopathological and molecular genetics features of LBL-IRF4 in adults diagnosed at the First Affiliated Hospital of Zhengzhou University between January 2016 and December 2024 were analyzed using immunohistochemistry and fluorescence in situ hybridization (FISH). Clinical information was also collected and analyzed. Results: Seventeen cases were reviewed. There were 5 male and 12 female patients, aged 19 to 68 years, with media age of 42.0(21.0,61.5) years. All patients presented with head and neck lesions, especially Waldeyer's ring and cervical lymphadenopathy (15/17). No bone marrow involvement was detected in any of the patients while most of them were at the Ann Arbor stage Ⅰ-Ⅱ (16/17). Morphologically, 11 cases had a diffuse growth pattern, and 6 cases had a follicular/diffuse growth pattern, exhibited medium to large lymphoid cells. Two cases showed a "starry sky" appearance, and 4 cases exhibited coagulative necrosis. Tumor cells were positive for CD20 and CD79a. CD10 was positive in 13 cases (13/17) while bcl-2 was positive in 12 cases (12/17). Bcl-6 and MUM-1 were positive in all cases. CD5 was expressed in 5 cases (5/17). All cases were EBV-negative (0/16). IRF4 rearrangement was identified in all cases. No breaks in MYC or bcl-2 were detected in any of the cases. Bcl-6 rearrangements were found in 8 cases (8/17) by FISH. All 17 patients received chemotherapy after the diagnosis. Sixteen patients at follow up were alive (1 case was lost to follow-up). Conclusions: LBL-IRF4 involving the head and neck in adults is not uncommon. Adult cases mimic their pediatric counterparts, showing similar morphological and immunohistochemical features. Some cases are CD5 positive and harbor bcl-6-rearrangement. Overall, it carries a favorable prognosis. Routine testing of IRF4 rearrangement is recommended for cases with the following characteristics: in the head and neck region, morphologically high-grade follicular lymphoma or diffuse large B-cell lymphoma with strong MUM-1 expression irrespective of patient age.

Objective: To investigate the clinicopathological characteristics of nodular fasciitis (NF) in children. Methods: Twenty-four cases of pediatric NF (including four cases of cranial fasciitis and one case of intravascular fasciitis) diagnosed at the Department of Pathology of Henan Children's Hospital from January 2013 to February 2025 were collected. Their clinical features and histological characteristics were retrospectively analyzed. Immunophenotyping was performed using the EnVision method, USP6 gene rearrangement was detected by fluorescence in situ hybridization (FISH), and follow-up information was obtained. Results: There were 17 male and 7 female patients. The median age was 5.0 (2.0, 8.5) years (interquartile range, 2.0-8.5). Sixteen cases of NF were identified in the head and neck. Superficial masses presented as gradually enlarged or persistence lesions, while a mesenteric mass presented with abdominal pain. No definite history of trauma was reported. Microscopically, the lesions showed diverse morphologies. Most lesions were ill-defined. The tumor cells were spindle-shaped fibroblasts/myofibroblasts within a myxoid stroma, arranged in a loosely woven pattern, and accompanied by extravasated red blood cells. Nearly half of the cases showed prominent collagen proliferation. Other uncommon morphological features included densely packed tumor cells, arranged in a woven pattern, and stroma with abundant foamy cells, dense inflammatory infiltrate, or multinucleated giant cells. Immunohistochemical staining was positive for SMA (24/24), Caldesmon (23/24), and Calponin (22/24). FISH analysis for USP6 rearrangement was positive in 22 of 24 cases; one case of decalcified specimen showed no signals, and the single case of intravascular fasciitis was negative. Follow-up data were available for 20 cases, and none of the patients experienced recurrence after complete surgical excision. Conclusions: Nodular fasciitis in children predominantly affects the head and neck of preschool-aged children. The lesion exhibits diverse histological features, and demonstrates a high positive rate for USP6 rearrangement by FISH. The prognosis is excellent following complete surgical excision.

Objective: To investigate the expression of anaplastic lymphoma kinase (ALK) in malignant melanoma and analyze its clinicopathological and molecular features. Methods: Eighty-seven malignant melanomas that were surgically resected at the First Affiliated Hospital, Zhejiang University School of Medicine between January 2015 and December 2019 were collected. Immunohistochemical staining was performed to evaluate ALK expression. Positive cases were further analyzed using clinical, pathological, and molecular testing data. Relevant literature was systematically reviewed, and follow-up was conducted. Results: Three cases showed ALK-positive expression. They were all in male patients, aged 52, 79, and 51 years, with tumors located in the left temporooccipital skin, maxillary gingiva, and left plantar skin, respectively. Cases 1 and 3 had a history of smoking and diabetes; case 2 had a history of alcohol use. Histologically, case 1 exhibited pagetoid spread with prominent lymphocytic infiltration; case 2 showed nodular growth with ulceration; while case 3, a recurrent lesion, was surrounded by abundant lymphocytes. All three cases displayed sheet-like proliferation of epithelioid or short spindle-shaped tumor cells, conspicuous nucleoli, and frequent mitoses. Marked pigmentation was observed in cases 1 and 3, but not in case 2. Fluorescence in situ hybridization (FISH) revealed ALK gene rearrangement in case 2, but not in cases 1 and 3. The nCounter analysis showed high expression of ALK exons 20-29 and intron 19 with low expression of exons 1-19 in cases 1 and 3, consistent with an alternative transcription initiation (ATI)-driven ALK expression pattern. In contrast, case 2 exhibited high expression of exons 20-29 but low expression of both exons 1-19 and intron 19, supporting an ALK fusion subtype. No mutations of KRAS, NRAS, BRAF, or PIK3CA were detected in any of the cases. Conclusions: Both ALK fusion and ATI-driven ALK expression patterns can present in malignant melanomas. Aberrant ALK activation suggests its potential role in molecular pathogenesis of malignant melanoma. Further investigation of ALK as a therapeutic target seems necessary.

Objective: To investigate the clinicopathological features, immunophenotype, molecular genetic characteristics, and prognosis of clear cell meningioma (CCM). Methods: Seventeen cases with diagnosed of CCM from four hospitals [Xuanwu Hospital (6 cases), Sanbo Brain Hospital (3 cases), Beijing Children's Hospital (4 cases) Affiliated with Capital Medical University; Provincial Hospital Affiliated to Shandong First Medical University (4 cases)], from August 2017 to April 2025, were analyzed. All specimens of CCM cases were H&E stained, followed by immunohistochemistry (IHC), next-generation sequencing (NGS), and DNA methylation profiling. Clinical follow-up and prognostic analysis were performed. Results: The cohort included six males and eleven females, with a median age of 11 (6, 44) years; 10 were pediatric patients, 7 were adult patients. None had neurofibromatosis type 2. Tumor locations included spinal canal (n=5), cerebellopontine angle (n=4), middle/posterior fossa (n=4), petroclival region (n=3), and jugular foramen (n=1). Histologically, tumors showed sheets of polygonal cells with clear glycogen-rich cytoplasm, round/oval nuclei with inconspicuous nucleoli, prominent perivascular and interstitial hyalinized collagen proliferation, and scattered lymphoplasmacytic infiltrates. No other meningioma subtypes were identified (17/17). IHC showed variable expression of EMA, vimentin, SSTR2, and PR, with universal loss of SMARCE1 nuclear expression. The median Ki-67 index was 6%. NGS revealed no NF2 alterations (0/10), while SMARCE1 mutations were detected in 9/10 of cases, including: 2 sites with splice-site mutations, 2 sites with nonsense mutations and 3 sites with frameshift mutations. DNA methylation unsupervised clustering demonstrated distinct profiles separating CCMs (8/33) from other meningiomas (25/33). Among 14 patients with follow-up (median 32 months, range 2-145 months), recurrence occurred in 6 cases and death in 1 case; all recurrence/death cases were pediatric patients. CCM patients had significantly higher recurrence/progression risk compared with WHO grades 1 and 2 meningiomas (HR=3.863, 95%CI: 1.435-10.401,P=0.02), with earlier recurrence. High Ki-67 index (≥10%) was associated with increased risk of recurrence (P<0.01). Conclusions: CCMs exhibit unique age distribution, anatomical predilection, histopathological changes, immunophenotype (SMARCE1 loss), and molecular profile (SMARCE1 mutations, distinct methylation signature). They demonstrate aggressive behavior, particularly in pediatric patients and cases with high proliferative activity, warranting close clinical surveillance and consideration of adjuvant therapy.