Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Objective:To investigate the clinicopathological and genetic features of infantile rhabdomyofibrosarcoma (IRFS) with EGFR kinase domain duplication (EGFR-KDD).Methods:The clinical, morphological and immunohistochemical features of three IRFS with EGFR-KDD diagnosed from January 2022 to January 2024 at Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed using PCR or next generation sequencing technique; and related literature was reviewed.Results:There were 1 male and 2 females, aged at presentation ranging from 1 to 4 years. The tumor occurred in the left thigh, right maxillofacial region, and right popliteal space. The presenting symptom was a painless mass which was accidentally discovered. The maximum diameter of tumors ranged from 3 to 5 cm. Microscopically, the tumors were poorly defined and composed of relatively monomorphic spindle cells, arranged in diffuse, fascicular growth patterns, with moderate pale eosinophilic cytoplasm. Mitoses were abundant. A few round rhabdomyoblastic tumor cells with abundant eosinophilic cytoplasm were found. There was no evidence of hemorrhage or necrosis. The tumor cells expressed vimentin, SMA, MSA, desmin, MyoD1 and myogenin; and the Ki-67 proliferation index was 10%-60%. RT-PCR showed EGFR-KDD in all three cases. Gene fusion was detected in three cases based on next generation sequencing, but only one case had EGFR-KDD. Follow-up data for 12 to 36 months showed two patients died of the disease and one patient was alive without recurrences and metastasis.Conclusions:IRFS is a rare soft tissue tumor that resembles infantile fibrosarcoma but has immunohistochemical evidence of rhabdomyoblastic differentiation. It more commonly occurs in infants and tends to appear in limbs and torso with poor prognosis. Aggressive multimodality treatment is recommended for these patients. EGFR-KDD may be a genetic driver to IRFS. Clinical response to EGFR targeted therapy might be promising in the future.

Objective:To investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

Objective:To investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity.Methods:The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review.Results:All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization.Conclusions:CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.

Objective:To investigate the clinicopathological and genetic features of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion.Methods:The clinical, morphological and immunohistochemical features of 14 cases of epithelioid and spindle cell rhabdomysarcoma with EWSR1-TFCP2 or FUS-TFCP2 fusion diagnosed from January 2019 to December 2022 in the Department of Pathology, Foshan Traditional Chinese Medicine Hospital, Foshan, China were retrospectively analyzed. The cases were all subject to FISH or next generation sequencing for analysis of molecular genetic features. The literature was reviewed.Results:There were 5 males and 9 females, with the age at presentation ranging from 6 to 36 years (mean, 22 years). Tumors occurred in the head and neck (9 cases), pelvic region (2 cases), bladder (one case), right humerus (one case), and the abdominal wall, humerus and pubic at the same time (one case). Presenting symptoms varied by location but often included pain or discomfort. Most of the patients showed aggressive radiographic features with soft tissue extension. The tumors had a median size of 6.6 cm (range, 2-23 cm). The tumors were poorly defined and irregularly shaped. Microscopic examination showed diffuse proliferation of spindle or epithelioid cells. While morphologically high-grade tumors displayed obvious cytological atypia, a high mitotic count and tumor necrosis, low-grade tumors grew in sheets and fascicles composed of spindle, epithelioid cells with moderate or abundant amounts of eosinophilic cytoplasm, without pronounced cytological atypia. The tumor cells expressed Desmin, MyoD1, and Myogenin, as well as ALK, EMA, and CKpan. EWSR1/FUS-TFCP2 gene fusion was detected in 14 cases with next generation sequencing and confirmed by FISH. Six cases had EWSR1-TFCP2 fusions and 8 cases showed FUS-TFCP2 fusions. Follow-up information was available in 13 patients, ranged from 5 to 37 months. At the end of follow-up period, 7 patients died of the disease. Six patients were alive:two cases had local recurrences and metastases, two cases of recurrences, one case of metastasis and one case without recurrences and metastasis.Conclusions:Epithelioid and spindle cell rhabdomysarcomas with EWSR1-TFCP2 or FUS-TFCP2 fusion show a very aggressive clinical course, and more commonly occur in the head and neck. Their genetic hallmark is the presence of EWSR1/FUS-TFCP2 fusions. Familiarity with its clinicopathological characteristics is helpful in avoiding misdiagnoses.

A 13-year-old female patient presented with itchy rashes on the right foot for 5 years. Skin examination revealed scattered flat, reddish-purple, slightly scaling papules on the inner side of the arch of the right foot, scattered light red papules on the outer side of the right great toe, and scattered domed reddish-purple papules on the right heel with collar-shaped keratinization around the base. Histopathological examination of the papule on the right heel revealed epidermal hyperkeratosis, marked hyperkeratosis around the papule, thickened granular layer and focal liquefaction degeneration of the basal layer with no obvious hyperplasia of the spinous layer; a large number of lymphocytes and plasma cells without atypia infiltrated the dermis, in which there were many small- and medium-sized dilated thick-walled blood vessels lined with prominent plump endothelial cells. The patient was diagnosed with acral pseudolymphomatous angiokeratoma of children, and treated with long-pulsed 1 064-nm Nd: YAG laser once every month. After 7 sessions of treatment, the rashes regressed and decreased in number.

A 25-year-old female patient presented with itchy rashes on her feet for 10 years. Skin examination showed dark red plaques with clear boundaries, whose surfaces were covered with grey-brown scales, on the dorsum of toes and adjacent dorsum of the feet, the extensor aspect of the right ankle and the left Achilles tendon. Laboratory tests revealed that serum anti-hepatitis C virus (HCV) antibody was negative and HCV-RNA quantity was normal. Histopathological examination showed epidermal hyperkeratosis with parakeratosis, irregularly thickened spinous layer, scattered dyskeratotic cells and necrotic keratinocytes in the middle and upper spinous layer, focal liquefaction degeneration of basal cells, dilatation of small blood vessels in the superficial and middle dermis, and perivascular infiltration of a small number of lymphocytes. The patient was diagnosed with necrolytic acral erythema without hepatitis C. After 2-month treatment, the skin lesions completely regressed, and hyperpigmentation remained.

Purpose To investigate the clinicopathologic features of desmoplastic fibroma of bone (DF).Methods The clinical and pathologic profiles of 7 cases were retrospectively analyzed.Results Desmoplastic fibroma of bone was a rare neoplasm of bone,which typically occurred in young children and adolescents.The tumor showed infiltrative and locally aggressive nature,the most common sites were long tubular bones and mandible.Microscopically,the tumor was composed of sparse fibroblasts in a rich background of collagen fibers.Immunohistochemically,the tumor cells were positive for vimentin and SMA.Conclusion Desmoplastic fibroma is a rare,locally aggressive fibroblasticlesion of bone.It can make an accurate diagnosis by integrating the clinical location with histopathological features.Trauma,hormone and horomosome aberration may be related with its pathogenesis.

OBJECTIVE:To establish a method for the content determination of AV45(the labeled precursor of PET agent for Aβ plaques)and its related substances. METHODS:HPLC method was performed on the column of Inertsil C18 with mobile phase of 50 mmol/L Disodium hydrogen phosphate solution- acetonitrile(containing 0.01% triethylamine)(15∶85,V/V)at a flow rate of 1.0 ml/min,the detection wavelength was 325 nm,and column temperature was 30 ℃,and volume injection was 20 μl. RESULTS:The AV45 and reaction intermediate as well as individual impurity peaks were well separated;the linear range was 200-1 000 μg/ml for AV45(r=0.999 2)and 20-100 μg/ml for intermediate(r=0.999 6);the detection limit and quantification limit of reaction in-termediate AV45 were 0.1 ng and 0.5 ng,respectively;RSDs of precision,stability and reproducibility tests were lower than 0.5%;recovery of AV45 was 98.93%-101.58%(RSD=0.69%,n=9). CONCLUSIONS:The method is simple and accurate with high specificity and good reproducibility,and suitable for content determination of AV45(the labeled precursor of PET agent for Aβplaques)and its related substances.

Purpose To investigate the clinicopathologic features of calcifying aponeurotic fibroma (CAF). Methods The clinical and pathologic profiles of 6 cases of CAF were retrospectively analyzed. Results CAF appeared a firm, painless and slowly growing mass with a predilection for the distal portions of the extremities in young children and adolescents. Microscopically, the tumor consis-ted mainly of benign appearing spindle cells, chondroid cells and calcific debris. Immunohistochemically, the tumor cells were positive for vimentin, HHF-35, S-100, Calponin and CD68. Conclusion CAF is a rare, locally aggressive fibroblastic lesion. It can make an accurate diagnosis by integrating the clinical location with histopathological features. Repeated minor trauma to the extremities and some embryologic cell nests maybe its pathogenesis.