Chondroid Synoviocytic Neoplasm: A Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of a Distinctive Tumor of Synoviocytes.

Tumors resembling tenosynovial giant cell tumor (TGCT) but additionally forming chondroid matrix are rare and most often involve the temporomandibular joint (TMJ). We studied 21 tumors consisting of synoviocytes (large, eosinophilic mononuclear cells containing hemosiderin) and chondroid matrix to better understand these unusual neoplasms. The tumors occurred in 10 males and 11 females, in the age group of 31 to 80 years (median, 50 years) and involved the TMJ region (16), extremities (4), and spine (1). As in conventional TGCT, all were composed of synoviocytes, small histiocytes, foamy macrophages, siderophages, and osteoclast-like giant cells in variably hyalinized background. Expansile nodules of large, moderately atypical synoviocytes were present, in addition to "chondroblastoma-like," "chondroma-like," or "phosphaturic mesenchymal tumor-like" calcified matrix. The synoviocytes expressed clusterin (17/19) and less often desmin (3/15). The tumors were frequently CSF1 positive by chromogenic in situ hybridization (8/13) but at best weakly positive for CSF1 by immunohistochemistry (0/3). Background small histiocytes were CD163 positive (12/12). All were FGF23 negative (0/10). Cells within lacunae showed a synoviocytic phenotype (clusterin positive; S100 protein and ERG negative). RNA-Seq was successful in 13 cases; fusions were present in 7 tumors, including FN1::TEK (5 cases); FN1::PRG4 (2 cases); and MALAT1::FN1, PDGFRA::USP35, and TIMP3::ZCCHC7 (1 case each). Three tumors contained more than 1 fusion (FN1::PRG4 with TIMP3::ZCCHC7, FN1::TEK with FN1::PRG4, and FN1::TEK with MALAT1::FN1). Clinical follow-up (17 patients; median follow-up duration 38 months; range 4-173 months) showed 13 (76%) to be alive without evidence of disease and 4 (24%) to be alive with persistent/recurrent local disease. No metastases or deaths from disease were observed. We conclude that these unusual tumors represent a distinct category of synoviocytic neoplasia, which we term "chondroid synoviocytic neoplasm," rather than simply ordinary TGCT with cartilage. Despite potentially worrisome morphologic features, they appear to behave in at most a locally aggressive fashion.

Prognostic Role of OX40, LAG-3, TIM-3 and PD-L1 Expression in Bone and Soft Tissue Sarcomas.

Introduction: The current study aims to evaluate the OX40, TIM-3, LAG-3, and PD-L1 targeted pathways in the regulation of T-cell activity in sarcoma patients to determine their relationship with overall survival (OS). Method: This study included one hundred and eleven patients with bone and soft tissue sarcoma diagnosed in two centers between 2010 and 2020. OX40, LAG-3, TIM-3 and PD-L1 expression levels were evaluated immunohistochemically from pathology preparations. Results: PD-L1 staining was detected in tumor cells, OX40, LAG-3, TIM-3 staining was detected in inflammatory cells in tumor tissue. In univariate analysis, no significant relationship was found between OX40, TIM-3, LAG-3, and PD-L1 staining and overall survival (respectively: p = 0.12, p = 0.49, p = 0.31, p = 0.95). When grade and stage at diagnosis, which were found to be significant in univariate analysis, along with OX-40, TIM-3, LAG-3, and PD-L1, were evaluated in multivariate analysis, a positive effect of OX-40 staining on overall survival was determined (p = 0.009). Considering the correlation between PDL-1 and OX40, TIM-3, and LAG-3 staining, a significant positive correlation was found between PDL-1 and TIM-3 and LAG-3 staining (respectively; p = 0.002, p = 0.001). Conclusions: There was no significant relationship between the PDL-1 staining percentage of tumor cells and OX40, TIM-3, and LAG-3 staining in inflammatory cells with the OS of sarcoma patients. However, detecting a significant positive correlation between PDL-1 staining and TIM-3 and LAG-3 staining also holds promise for finding effective targetable combination therapies that can prolong survival in sarcoma patients in the future.

The importance of diffusion apparent diffusion coefficient values in the evaluation of soft tissue sarcomas after treatment.

PURPOSE: In our study, we aimed to show the efficiency of diffusion-weighted images at different b-values and apparent diffusion coefficient (ADC) values in the differentiation of recurrent tumours from post-treatment tissue changes. MATERIAL AND METHODS: The conventional and diffusion magnetic resonance images (MRIs) of 42 patients operated for soft tissue sarcomas between June 2012 and March 2015 followed up with MRIs that were evaluated by 2 radiologists retrospectively. Diffusion MRIs were acquired at 4 different b-values (50, 400, 800, 1000 s/mm2). The lesions were classified according to conventional MRI findings as post-treatment changes and recurrent tumours. RESULTS: When the patient group with recurrent tumours was compared with the patient group with postoperative changes the ADC calculations were statistically significantly lower for the recurrent tumours at all b-levels (p < 0.001 for all b-levels). The sensitivity of b-50 values lower than 3.01 × 103 mm2/s in showing recurrent tumours was 100% and the specificity was 77.78%. The sensitivity of b-400 values lower than 2.1 × 103 mm2/s in showing recurrent tumours was 80% and the specificity was 96.3%. The sensitivity of b-800 values lower than 2.26 × 103 mm2/s in showing recurrent tumours was 100% and the specificity was 88.89%. The sensitivity of b-1000 values lower than 2 × 103 mm2/s in showing recurrent tumours was 93.3% and the specificity was 92.5%. CONCLUSIONS: The ADC values obtained from diffusion-weighted images have high sensitivity and specificity in differentiating recurring soft tissue sarcomas during monitoring after treatment from postoperative changes.

Sclerosing epithelioid fibrosarcoma of bone: morphological, immunophenotypical, and molecular findings of 9 cases.

Primary sclerosing epithelioid fibrosarcoma (SEF) of bone is a rare and scarcely reported neoplasm. We document clinicopathological and molecular features of 9 additional cases. Five males and 4 females had a mean age of 39 years (14-71 years). Most tumors affected flat/irregular bones; only 3 cases involved a long bone. By radiology, it has characteristic radiographic features of a predominantly lytic expansile lesion with a sclerotic rim. Referring diagnoses were SEF (n = 2), low-grade osteosarcoma (n = 2), chondrosarcoma (n = 1), and chondromyxoid fibroma (n = 1). Histologically, five cases revealed classical morphology of SEF of soft tissue. Remaining cases were classified as hybrid SEF/low-grade fibromyxoid sarcoma, characterized by spindle or stellate cells, prominent stroma, and giant hyalinized areas. Various morphological deviations such as prominent vasculature (n = 3), osteoid-like material (n = 4), or parallel bone trabeculae (n = 2) were observed. Immunohistochemically, all cases showed diffuse and strong MUC4 expression. SATB2 was observed in 5/8 cases. Using FISH, EWSR1, and FUS rearrangements were detected in 4 cases and 1 case, respectively. EWSR1-CREB3L1 fusion was identified in 1 additional case by next-generation sequencing. Recurrence and metastasis were observed in 1 case and 2 cases, respectively. All but one patient were alive with disease for a mean interval of 31 months. SEF of bone is a relatively indolent sarcoma of adults, most commonly located in the flat/irregular bones. Due to overlapping histological features, it is often misdiagnosed as osteosarcoma or a chondroid tumor. Most SEF of bone exhibit EWSR1 rearrangements, but rare cases may harbor a FUS gene fusion.

p16 expression predicts neoadjuvant tumor necrosis in osteosarcomas: reappraisal with a larger series using whole sections.

The presence of greater than or equal to 90% necrosis after neoadjuvant chemotherapy is a favorable prognostic factor in osteosarcomas. A recent study using tissue microarrays of 40 conventional osteosarcomas showed that p16 expression independently predicted the necrotic response to neoadjuvant chemotherapy. In this study, we investigated this finding using whole sections in a larger group of osteosarcomas. Cases of 83 patients who had pretreatment biopsies and received neoadjuvant chemotherapy and surgical resection were collected from 3 reference hospital archives. Age, sex, tumor size, tumor subtype, location, and percentage of tumor necrosis were recorded; 4-µm sections from pretreatment biopsies were stained for p16. More than 30% strong nuclear staining was regarded as positive. The median age was 17 years (5-68 years), and male/female ratio was 2.3. The mean tumor diameter was 9.9 cm (2-30 cm). Tumors were most commonly of the osteoblastic type (60%) and located at the femur (47%). p16 positivity was seen in 66% of the patients. The median pathologic necrosis was 65%, and 39% of the patients responded favorably (≥%90 necrosis) to neoadjuvant therapy. In univariate analysis, p16 expression significantly correlated with greater than or equal to 90% response (P = .022). On multivariate analysis, p16 expression (odds ratio [OR], 7.71; P = .008), female sex (OR, 8.62; P = .006), and smaller tumor size (OR, 0.86; P = .023) were independent predictors of favorable response to neoadjuvant chemotherapy. We confirmed the finding that p16 expression predicts postchemotherapy necrotic response in conventional osteosarcomas.

Factors in sample volume and quality of CT-guided vertebral biopsy: location and needle trajectory.

AIM: To assess sample volume (by its length and diameter) and sample quality (judging by its integrity) in CT-guided vertebral biopsy due to lesion location and needle trajectory method as individual study variables each. MATERIAL AND METHODS: Of 48 patients, 25 were men and 23 were women; ranging from 33 to 85 years of age, with a median age of 65.5 years. The independent variables were primarily vertebral location and needle trajectory. Two cervical lesions were excluded from location analysis. We examined sample length and width, and macroscopic (5-scale) and microscopic (3-scale) scores as dependent variables. We did not encounter with any major complication and infection. RESULTS: Median sample length and sample diameter were found to be 10 mm and 2 mm, respectively. No relation was observed between the dependent variables and location in the spine. There was a relation between sample length and needle trajectory (p=0.002) with values of 11 mm in the transpedicular method vs. 6 mm in the posterolateral method (p=0.01). CONCLUSION: Transpedicular trajectory had an advantage over the posterolateral method as it provides a longer sample. We believe that transpedicular biopsy should be preferred. Nevertheless, studies are needed to validate the most advantageous standard access position in spine biopsies.

Malignant conjunctival tumors invading the orbit.

AIM: The aim of this study is to present the clinical and histopathological features as well as the treatment results of advanced conjunctival malignant tumors with orbital invasion, in the context of all secondary orbital tumors. METHODS: A total of 151 secondary orbital tumors were observed over a 10-year period; 21 (14%) out of 151 cases were detected to be of conjunctival origin, and the cases were reviewed retrospectively. The age, gender, duration of symptoms, clinical and histopathological features and the treatment results of patients were recorded. RESULTS: Four out of 21 patients had malignant melanoma (MM), while 17 had squamous cell carcinoma (SCC) of the conjunctiva. The mean duration of symptoms was 11.3 months in the MM and 18.5 months in the SCC group. Perineural invasion was detected in 1 of the MM and 3 of the SCC cases. The peritumorous inflammation score was higher in the SCC than the MM group (2.2 vs. 1.5). Two patients underwent wide excision with control of the surgical margins and postoperative adjunctive topical chemotherapy. Nineteen patients needed exenteration. Two patients with regional metastasis were treated by radical neck dissection and radiation therapy to the neck. After a mean follow-up time of 35.6 months, no tumor recurrence or tumor-related death was encountered. Seven patients died from non-tumor-related causes. CONCLUSION: Delay in presentation for treatment and previous unsuccessful surgery of conjunctival malignant lesions are likely to lead to orbital invasion and loss of the eye. Exenteration is generally needed but margin-controlled wide surgical excision and adjuvant chemotherapy may be curative in selected cases. Early diagnosis and effective treatment of lesions will minimize the mortality rate and morbidity related to the disease.

Basal cell carcinoma of the eyelids and periorbital region in a Turkish population.

PURPOSE: To review the clinical and histopathologic features, treatment, and outcomes of eyelid basal cell carcinomas. METHODS: The clinical records and histopathologic specimens of 311 patients with eyelid basal cell carcinomas were reviewed and analyzed retrospectively. The main outcome measures are patient demographics, clinical characteristics, lesion size, duration of lesion, histologic subtypes, presence of orbital and perineural invasion, severity of peritumorous inflammation, treatment modalities, recurrence rate, tumor-related death, and prognostic features. RESULTS: Two-hundred ninety patients underwent surgery whereas others received radiotherapy or chemotherapy. The most common histologic subtypes were infiltrative, nodular, and basosquamous basal cell carcinomas. Nearly one-third (29.9%) of the patients were previously recurrent. Orbital and perineural invasion rates were 17.04% and 10.6%, respectively. Recurrent basal cell carcinomas were larger, with longer duration of lesion and a higher rate of orbital and perineural invasion. Basosquamous basal cell carcinomas were more likely to have prior recurrences, larger lesion size, and the highest rate of orbital invasion. Perineural invasion was most frequent in morpheaform and basosquamous subtypes. Peritumorous inflammation differed between subtypes and was highest in the superficial subtype. The recurrence rate was 7.39% in total. The death of 2 patients was tumor-related. CONCLUSIONS: In this large case series from a single center, the outcomes were worse than previously reported due to delay in treatment and previous inadequate treatments. Adverse prognostic factors associated with secondary orbital invasion are previous recurrences, aggressive histologic subtypes, longer duration of lesion, larger lesion size, and the presence of perineural invasion.