Pleomorphic Tumor Research Articles

Atypical Uterine Leiomyoma: A Case Report and Literature Review

Introduction: Atypical leiomyomas are diagnosed histologically, showing pleomorphic atypical tumor cells with low mitotic counts and no coagulative necrosis. Surgical treatment is indicated when abnormal uterine bleeding or symptoms related to the size of the leiomyomas, infertility, or recurrent gestational loss are presented. Clinical case: A 40-year-old woman with a history of menstrual changes, abdominal pain, and intermenstrual bleeding was scheduled for surgery. Pathology reported an atypical leiomyoma (23x18x13 cm) with myxoid degeneration. Discussion: Uterine leiomyomas affect 70-80% of women in their reproductive age. Symptoms vary by size and location, including abnormal bleeding, pain, and pressure-related issues. This patient had a single pedunculated leiomyoma, no endometrial hyperplasia, negative cervical cytology, and uterine adhesions. Myomectomy was chosen to avoid organ damage. Conclusion: Atypical leiomyomas are rare tumors diagnosed through biopsy and histopathological examination, displaying 10 mitoses per field and no necrosis. Immunohistochemical studies are necessary to distinguish them from leiomyosarcoma. Long-term follow-up after myomectomy is essential to monitor for recurrence.

Is intercalary frozen autograft augmented with intramedullary cement and bridging plates fixation a durable reconstruction?

AimsWe analysed the survival, complications, and function of frozen autograft augmented with intramedullary cement and bridging plates fixation for intercalary bone defect reconstruction in primary bone sarcomas.Patients and MethodsA retrospective cohort study was conducted on 72 patients with primary bone sarcomas (34 males, 38 females) between January 2016 and June 2023. The average age was 22.0 ± 13.6 years (6 to 61 years) and the pathological type included osteosarcoma (55), followed by adamantinoma (5), Ewing’s sarcoma (4), undifferentiated pleomorphic sarcoma (4), chondrosarcoma (3), and malignant tenosynovial giant cell tumor (1). The oncological outcomes included local control, metastasis, progression-free survival and overall survival. The functional outcomes were evaluated by the Musculoskeletal Tumor Society Score (MSTS-93), the Toronto Extremity Salvage Score (TESS), and the motion of the joint.ResultsThe mean follow-up time was 50.0 ± 27.4 months (12 to 99 months). 10 patients died of the disease, 9 patients were alive with disease and 53 patients were alive with no evidence of disease. The average 5-year overall survival of autograft was 85.8% (95% CI, 72.1-93.1%). The average MSTS-93 score was 96% ( 67–100%) and the average TESS score was 98% (74–100%). Twenty-four patients (33.3%) had at least one complication in the follow-up period. The most common complications were nonunion (9.7%, 7/72) and local recurrence (9.7%, 7/72), followed by leg length discrepancy (6.9%, 5/72), infection (5.6%, 4/72), implant failure (4.2%, 3/72), delayed union (2.8%, 2/72), and graft fractures (1.4%, 1/72). Tumor site was an independent risk factor for bone nonunion (OR, 22.23; p = 0.006).ConclusionsWe presented a large technique series for preventing autograft-related complications (especially for autograft fractures) of intercalary frozen autograft reconstruction. This method showed promising functional outcomes and provided durable reconstruction.Level of evidencelevel IV therapeutic study.

A Comprehensive Insight Into Primary Intimal Sarcoma of the Pulmonary Artery; From Diagnosis to Management: A Case Report and Review of the Literature.

Primary intimal sarcoma of the pulmonary artery is a rare and aggressive malignancy that presents significant diagnostic and therapeutic challenges due to its nonspecific symptoms and propensity for late detection. This case report aimed to elucidate the diagnostic journey, surgical intervention, and multidisciplinary management of this rare entity. In September 2023, a 42-year-old male presented with dyspnea on exertion and retrosternal chest pain, classified as NYHA FC II. Initial investigations, including ECG and lab tests, indicated tachycardia and elevated troponin and NT-pro-BNP levels. Transthoracic and transesophageal echocardiography identified a multilobulated mass in the right ventricular outflow tract and main pulmonary artery. Cardiac MRI and CT angiography confirmed a high-grade pleomorphic spindle cell tumor, leading to surgical resection in October 2023. Histopathology confirmed intimal sarcoma. Postsurgery, the patient underwent chemotherapy and radiotherapy, showing significant clinical improvement and no recurrence on follow-up PET-CT. This case highlights the importance of a multidisciplinary approach in diagnosing and managing primary intimal sarcoma of the pulmonary artery, emphasizing the role of advanced imaging, timely surgical intervention, and combined chemotherapy with radiotherapy in improving patient outcomes.

Unveiling a rare haemorrhagic malignant pleural effusion: The role of medical thoracoscopy in diagnosing primary pleural angiosarcoma.

Primary pleural angiosarcoma (PPA) is a rare and challenging tumour to diagnose, often mistaken for other malignancies such as mesothelioma and lung cancer due to overlapping clinical and imaging features. We report a 52-year-old woman who presented with progressive shortness of breath and pleuritic chest pain. Imaging studies and thoracentesis revealed a large haemorrhagic left pleural effusion. Medical thoracoscopy (MT) showed a thickened and lobulated parietal pleura with multiple nodular lesions. Histopathological examination confirmed a diagnosis of angiosarcoma, characterized by pleomorphic tumour cells, a high Ki67 proliferation index and positive immunohistochemical markers, including CD31, D2-40, Vimentin, and Factor VIII. Tragically, the patient developed a hospital-acquired infection and passed away before any definitive treatment for the angiosarcoma could be initiated. This case underscores the diagnostic complexities of PPA and highlights the utility of MT in identifying this rare malignancy.

Histology-Specific Clinical Trial of Lenvatinib and Pembrolizumab in Patients with Sarcoma.

Survival of patients with metastatic sarcoma remains poor, and there is a pressing need for new therapies. Most sarcoma subtypes are not responsive to immune checkpoint inhibition alone. Lenvatinib, a multireceptor tyrosine kinase inhibitor targeting tumor vasculature, has an immunomodulatory activity that contributes to its antitumor effects. Therefore, we hypothesized that a combination of lenvatinib and pembrolizumab would lead to improved clinical outcomes in patients with sarcoma. This was an open-label, single-arm study of lenvatinib and pembrolizumab in the following cohorts: (A) leiomyosarcoma, (B) undifferentiated pleomorphic sarcoma (UPS), (C) vascular sarcomas (angiosarcoma and epithelioid hemangioendothelioma), (D) synovial sarcoma or malignant peripheral nerve sheath tumor (MPNST), and (E) bone sarcomas (osteosarcoma and chondrosarcoma). The primary endpoint was the best overall response (BOR) rate documented by RECIST v1.1 by 27 weeks in each cohort, with a threshold of ≥2 responses among 10 patients. Secondary endpoints included progression-free survival, overall survival, duration of response, and safety. Forty-six patients were evaluable for the primary endpoint, which was met in the UPS and MPNST/synovial cohorts (BOR rates by 27 weeks of 25% and 30%, respectively). There were seven partial responses overall with additional responses noted in angiosarcoma and osteosarcoma. Treatment-related adverse events of any grade and grade 3 or higher occurred in 50/51 (98%) and 29/51 (57%) of patients, respectively. We observed durable responses in MPNST, synovial sarcoma, and osteosarcoma. Patients with UPS and angiosarcoma also responded. Further exploration of this approach is warranted to confirm activity and determine optimal dosing schedules.

Clinical Outcomes and Complications of Parotidectomy for Pleomorphic Adenoma Tumour

Objective: To evaluate the clinical and surgical outcomes in patients treated for pleomorphic adenoma (PA) of the parotid gland. Methods: This retrospective study covered 100 PA cases from 2000 to 2018, all confirmed by histopathology and with at least 24 months of follow-up. Statistical analysis was performed using Student’s t-test, Pearson’s Chi-square test, and Fisher’s exact test, with a significance level of 0.05. Results: The average patient age was 42±12 years, with an even sex ratio. Parotid swelling was the main symptom (94%), with an average tumor size of 2.5cm. Most tumors were in the superficial lobe (94 cases), and there were 3 bilateral cases. Surgical approaches included superficial exofacial parotidectomy (55 cases), total parotidectomy (25 cases), partial exofacial parotidectomy (14 cases), and enucleation (6 cases). Complications occurred in 49 patients, with postoperative facial paralysis (FP) being the most common (20%). Total parotidectomy had a higher transient FP rate (24%) compared to exofacial parotidectomy (11%). Four recurrences were noted, mainly after enucleation or exofacial parotidectomy. Statistical analysis showed significant associations: exofacial parotidectomy had the highest complication rate (47%) and was linked to permanent FP (p=0.02). Total parotidectomy was associated with Frey’s syndrome (p=0.01), partial exofacial parotidectomy with salivary fistula (p<0.001), and enucleation with tumor recurrence (p<0.001). Conclusions: Superficial exofacial parotidectomy is common but associated with complications. Total parotidectomy is linked to Frey’s syndrome, while partial exofacial parotidectomy and enucleation have specific risks of salivary fistula and recurrence. Careful selection of surgical technique is crucial to minimize complications and recurrence.

Pleomorphic Liposarcoma Cytologically Detected in Hemosiderotic Pleural Effusion: Pitfalls Mitigated by Cytologic Clues and Cellblock Immunocytochemistry.

Sarcomatous serous effusions are uncommon and diagnostically challenging. Dedifferentiated and pleomorphic liposarcomas are rare tumors in pleural effusions revealing highly pleomorphic tumor cells mimicking carcinoma, mesothelioma, melanoma, and other sarcomas. Hematothoracic effusions further complicate the cytologic diagnosis. Correct cytologic recognition is important. We report pleomorphic liposarcoma cytologically detected in effusion fluid in a 56-year-old man who presented with a massive unilateral pleural effusion. ThinPrep showed hemorrhagic effusion fluid characterized by lysed red blood cells, foamy macrophages, and siderophages intermixed with highly pleomorphic predominantly naked mononuclear and giant nuclei. The aggregated siderophages and vacuolated macrophages could be mistaken for tumor cells, whereas the bare nuclei may be missed as nonspecific degenerate changes. Cellblock sections showed highly pleomorphic mononuclear and multinucleated giant tumor cells with diagnostic lipoblasts, intermixed with foamy macrophages and siderophages. Cellblock immunocytochemistry showed staining for vimentin and S-100 protein in the tumor cells. Other lineage-specific immunomarkers were negative. CD68 and calretinin revealed frequent background macrophages and scarce mesothelial cells. The tumor cells were negative for MDM2 and CDK4. The entertained cytopathologic diagnosis was pleomorphic liposarcoma. Core needle biopsy was procured from the mass. The histopathologic features and immunoprofile of the tissue specimen matched the cytopathologic and immunocytochemical findings confirming the cytologic diagnosis of pleomorphic liposarcoma. Pleomorphic liposarcoma is an unexpected cytologically challenging finding in effusions, particularly when compounded by pitfalls introduced by hemosiderotic fluid. Attention to certain cytologic clues mitigate pitfalls. Cellblock is a valuable diagnostic tool when integrated with relevant negative and positive immunocytochemical markers.

Giant cell carcinoma of the urinary bladder

We present the clinicopathological features of 23 cases of the giant cell subtype of urothelial carcinoma, a rare subtype of bladder cancer recognized in the current World Health Organization classification of urological tumors. Histologically, the architectural pattern of the tumor varied from infiltrating to the solid expansile pleomorphic tumor with giant, bizarre, anaplastic cells. Typical or atypical mitotic figures were frequently present in all cases. Between 10 and 30% of the tumor had a giant cell component. All cases were associated with conventional high-grade urothelial carcinoma, with areas of squamous cell divergent differentiation and micropapillary carcinoma present in six and two cases, respectively. In one case each had sarcomatoid, nested, small cell, or glandular divergent differentiation. At diagnosis, 35% of patients had advanced disease and 12% had distant metastases. When comparing giant cell urothelial carcinoma with conventional urothelial carcinoma in a matched analysis, differences in overall and cancer-specific survival were observed, particularly in the T1 stage category. Immunohistochemical staining showed a similar profile of urothelial lineage with frequent positive expression of uroplakin II, GATA3, CK20, CK7, and S100P in both giant cell and conventional urothelial carcinomas. High Ki67 proliferation (range, 60–90%; mean, 71%) and nuclear p53 accumulation (mutant profile; range, 50–90%; mean, 64%) were observed. Using the 22C3 assay, the expression of PD-L1 was found to be variable in two cases, and beta-HCG was negative. In conclusion, giant cell carcinoma is a subtype of urothelial carcinoma associated with advanced clinical stage and a trend to lower survival rates.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas: a narrative review.

Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas (UCOGCP) is a rare pancreatic tumor that accounts for less than 1% of all pancreatic malignancies. The characteristic pathological manifestation of UCOGCP is the presence of osteoclast-like giant cells (OGCs) distributed among pleomorphic undifferentiated tumor cells. UCOGCP can occur either alone or in association with other types of pancreatic tumors. At present, there is no unified consensus or guideline for the diagnosis and treatment of UCOGCP, and most of the literature are individual case reports. With the accumulation in the number of clinical cases and the development of precision medicine technology, the understanding of UCOGCP is also deepening. Researchers have begun to recognize that UCOGCP is a pancreatic tumor with distinctive clinical and molecular characteristics. In this review, we focus on the latest research status and future exploration directions in the diagnosis, treatment, and prognosis of UCOGCP.

Atypical Spindle Cell/Pleomorphic Lipomatous Tumor With Sarcomatous Transformation: Clinicopathologic and Molecular Analysis of 4 Cases

Atypical spindle cell/pleomorphic lipomatous tumor (ASPLT) is a recently described adipocytic tumor predominantly affecting the subcutaneous soft tissues of adults. Previous studies have shown that ASPLT follows a benign clinical course with a 4% to 12% local recurrence rate and no risk of dedifferentiation. Herein, we describe the clinicopathologic and molecular findings of 4 cases of ASPLT showing unequivocal sarcomatous transformation. Three patients were male and one was female, aged 65, 70, 74, and 78 years. Two cases presented as mass-forming lesions, while 1 case was incidentally discovered. The tumors measured 30, 55, 80, and 110 mm and occurred in the chest wall (n = 2) or arm (n = 2); all were subcutaneous. Microscopically, they showed a biphasic appearance comprising a low-grade ASPLT component and a high-grade sarcomatous component. The low-grade components showed features in the spectrum of either atypical pleomorphic lipomatous tumor (n = 2) or atypical spindle cell lipomatous tumor (n = 2). The high-grade components displayed leiomyosarcoma-like (n = 2), pleomorphic liposarcoma-like (n = 1) or undifferentiated sarcoma-like (n = 1) morphology. On immunohistochemistry, tumors were negative for MDM2 and showed loss of RB1 expression. In addition, the leiomyosarcoma-like areas seen in 2 cases were positive for smooth muscle actin and H-caldesmon. Single-nucleotide polymorphism array, performed in 3 cases, showed deletions of TP53, RB1, and flanking genes in both components. In contrast, the sarcomatous components showed more complex genomic profiles with rare segmental gains and recurrent loss of PTEN (n = 3), ATM (n = 2), and CDKN2A/B (n = 2) among other genes. Whole exome sequencing identified a TP53 variant in one case and an ATRX variant in another, each occurring in both tumor components. Limited clinical follow-up showed no recurrence or metastasis after 1 to 13 months (median, 7.5 months) postsurgical excision. Altogether, our data support that ASPLT can rarely develop sarcomatous transformation and offer insights into the molecular mechanisms underlying this event.

DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5′) and centromeric (3′) amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5′-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5′-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5′-predominant amplification, can be reclassified out of the UPS category.

Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review.

Dedifferentiation is a very rare phenomenon in uterine leiomyosarcoma (LMS). The aim of this study was to comprehensively analyze the clinicopathological characteristics of uterine dedifferentiated LMS (DDLMS). We reviewed electronic medical records and pathology slides from five patients with uterine DDLMS and performed immunostaining. The mean age of the patients was 56 years. Two patients presented with abdominal discomfort, while in three cases the uterine tumors were detected on routine medical examination. The mean size of the tumors was 17.0 cm. Four patients underwent hysterectomy. The initial stages were distributed as IB (2/5), IIIC (2/5), and IVC (1/5). Post-operative concurrent chemoradiation therapy, radiation therapy, and chemotherapy were administered in one, one, and two patients, respectively. Despite post-operative treatment, three patients developed metastatic recurrences in the abdominal and pelvic organs. Recurrence-free survival time ranged between 4 and 30 months. Histologically, the differentiated areas demonstrated the classic morphology of malignant smooth muscle differentiation, whereas the dedifferentiated areas resembled undifferentiated pleomorphic sarcoma and were characterized by large pleomorphic tumor cells admixed with haphazardly arranged atypical cells with marked nuclear pleomorphism. All cases also exhibited heterologous components, including chondrosarcoma (CSA; 3/5) and rhabdomyosarcoma (2/5). In two cases, the heterologous components were initially detected in primary tumors. In three cases, the primary tumors did not exhibit any dedifferentiated or heterologous components. Instead, more than half of the recurrent tumors consisted of heterologous components. Three cases showed a sharp demarcation between the LMS and CSA components, while in two cases the dedifferentiated area imperceptibly merged with the differentiated component. Immunostaining revealed that the dedifferentiated components exhibited a lack of desmin immunoreactivity in three of the four examined cases. A subset of uterine LMS represents various amounts and types of dedifferentiation and heterologous components in both primary and recurrent tumors. Routine recognition of DDLMS and distinction from its mimickers are required for accurate diagnosis and further characterization of these rare tumors.

Evolving Pink Papule in a Young Female

Eccrine porocarcinoma (EPC) is a rare cutaneous adnexal tumor derived from sweat glands. Typically, EPC presents as a nonspecific erythematous papule or nodule most commonly on the head, neck, or lower extremities of females in the sixth or seventh decade of life. This tumor may arise from an existing benign eccrine poroma or occur de novo. Herein, we report a case of a growing erythematous nodule with overlying telangiectasia on the lower extremity of a woman in her twenties. Biopsy revealed a cyst-like lesion beneath the epidermis comprised of clear fluid material. Both solid and cystic components were present alongside pleomorphic tumor cell aggregates characterized by mitotic figures, hyperchromasia, and necrosis. The combination of clinical presentation and the presence of ductal structures on histopathologic analysis led to a diagnosis of EPC. This case reinforces the critical importance of histopathologic analysis of a nonspecific lesion that has evolved over time and may resemble other forms of cutaneous malignancy.

Cross-species evaluation of fibroblast activation protein alpha as potential imaging target for soft tissue sarcoma: a comparative immunohistochemical study in humans, dogs, and cats.

Complete surgical tumor resection is paramount in the management of soft tissue sarcoma (STS) in humans, dogs, and cats alike. Near-infrared targeted tracers for fluorescence-guided surgery (FGS) could facilitate intraoperative visualization of the tumor and improve resection accuracy. Target identification is complicated in STS due to the rarity and heterogeneity of the disease. This study aims to validate the expression of fibroblast activation protein alpha (FAP) in selected human, canine, and feline STS subtypes to assess the value of FAP as a target for FGS and to validate companion animals as a translational model. Formalin-fixed and paraffin-embedded tissue samples from 53 canine STSs (perivascular wall tumor (PWT), canine fibrosarcoma (cFS), and STS not further specified (NOS)), 24 feline fibrosarcomas, and 39 human STSs (myxofibrosarcoma, undifferentiated pleomorphic sarcoma, dermatofibrosarcoma protuberans, and malignant peripheral nerve sheath tumor) as well as six canine and seven feline healthy controls and 10 inflamed tissue samples were immunohistochemically stained for their FAP expression. FAP labeling in tumor, peritumoral, healthy skin, and inflamed tissue samples was quantified using a visually assessed semiquantitative expression score and digital image analysis. Target selection criteria (TASC) scoring was subsequently performed as previously described. Eighty-five percent (85%) of human (33/39), 76% of canine (40/53), and 92% of feline (22/24) STSs showed FAP positivity in over 10% of the tumor cells. A high expression was determined in 53% canine (28/53), 67% feline (16/24), and 44% human STSs (17/39). The average FAP-labeled area of canine, feline, and human STSs was 31%, 33%, and 42%, respectively (p > 0.8990). The FAP-positive tumor area was larger in STS compared to healthy and peritumoral tissue samples (p < 0.0001). TASC scores were above 18 for all feline and human STS subtypes and canine PWTs but not for canine STS NOS and cFS. This study represents the first cross-species target evaluation of FAP for STS. Our results demonstrate that FAP expression is increased in various STS subtypes compared to non-cancerous tissues across species, thereby validating dogs and cats as suitable animal models. Based on a TASC score, FAP could be considered a target for FGS.

DP08 Next-generation sequencing: the future for malignant melanoma diagnostic precision? A case of a BAP1 mutation

Abstract A 48-year-old man presented to the hand surgeons with a 5-year history of a subcutaneous swelling on his right wrist, associated with paraesthesia and pain, initially thought to be a benign ganglion. Excision biopsy of the lesion on histology revealed an encapsulated pleomorphic tumour attached to a nerve, thought to represent a sarcoma. Immunohistochemistry showed a positive reaction to S100, SOX10, calretinin and synaptophysin. Ki67 showed a 20% proliferation index. Multiple pathology opinions were sought, and further testing was performed at a specialist genomic laboratory. Detailed questioning regarding family history of malignancy revealed that the patient’s mother had died from metastatic uveal melanoma, a maternal aunt had died of a brain tumour and his maternal grandmother had lung cancer. Pan-cancer gene panel DNA next-generation sequencing showed a BAP1 mutation with a very high variant allele fraction, suggestive of germline inheritance. Given the clinical history, morphology, immunoprofile and DNA result, a favoured diagnosis of metastatic malignant melanoma with a BAP1 mutation was made. The patient was referred to the specialist skin cancer multidisciplinary team meeting and reviewed by the dermatology team. Full skin check examination revealed two long-standing atypical naevi (&amp;gt; 10 years), one on the left forearm and another on his back, and these were excised urgently. Histology of the back lesion showed a polypoid melanocytic tumour comprising large epithelioid melanocytes with mild-to-moderate nuclear pleomorphism, multinucleated cells and intranuclear inclusions. This was in keeping with a pT4a nodular malignant melanoma with 7-mm Breslow thickness, associated with BAP1-inactivated syndrome. Histology of the left forearm lesion was consistent with a combined BAP1-inactivated melanocytoma, otherwise known as a ‘BAPoma’. An ophthalmology review did not identify a primary uveal melanoma. Staging scans of his chest, abdomen and pelvis and magnetic resonance imaging of his head showed no evidence of metastatic disease. The patient was referred for genetics counselling, wide local excision of the melanoma on his back, for consideration of adjuvant therapy with oncology and long-term follow-up with dermatology. BAP1 tumour predisposition syndrome is a newly recognized cancer syndrome that predisposes the patient to uveal melanoma, malignant mesothelioma, renal cell carcinoma, cutaneous melanomas and a range of other cancers (Masoomian B, Shields JA, Shields CL. Overview of BAP1 cancer predisposition syndrome and the relationship to uveal melanoma. J Curr Ophthalmol 2018; 30:102–9). BAP1-related cancers tend to occur earlier in life and are more aggressive. Our case highlights the need for early identification of germline mutations through sequencing to improve outcomes and treatment-related morbidity by early diagnosis in these rare cancer syndromes.

Thoracic SMARCA4-deficient undifferentiated tumor with associated granulomatous reaction and response to pembrolizumab.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a rare entity that was recently described in the current World Health Organization Classification of Tumors. These lesions are highly aggressive with dismal prognosis, and most patients present with metastasis at the time of diagnosis. While there are about 100 cases of SMARCA4-UT described in the literature, there are only few existing reports that describe the cytomorphology of these lesions. We present a patient with masses involving the mediastinum, right lung, right supraclavicular lymph node and right adrenal gland. Subsequent core-needle biopsy of the right supraclavicular lymph node showed epithelioid to pleomorphic tumor cells with prominent nucleoli and associated granulomatous inflammation. The tumor cells were positive for CD34 and synaptophysin, and were negative for cytokeratins. SMARCA4 and SMARCA2 both showed loss of expression, which led to the diagnosis of SMARCA4-UT. The patient underwent treatment with pembrolizumab (PD-1 blocker), carboplatin, etoposide, and radiotherapy, resulting in an almost 55% reduction in the size of the primary tumor. Our case illustrates that an associated granulomatous inflammation might be an uncommon presentation of an already rare malignancy, and awareness of this phenomenon would prevent from mistaking SMARCA4-UT for other more well-known entities that can present with granulomas.

Lipoblastoma-Like Tumor and Fibrosarcoma-Like Lipomatous Neoplasm Represent the Same Entity: A Clinicopathologic and Molecular Genetic Study of 23 Cases Occurring in Both Men and Women at Diverse Locations

Lipoblastoma-like tumor (LLT) is a benign soft tissue tumor demonstrating mixed morphologic features of lipoblastoma, myxoid liposarcoma, and spindle cell lipoma but lacking genetic alterations associated with those tumors. LLT was originally thought to be specific to the vulva but has since been reported in the paratesticular region. The morphologic features of LLT overlap with those of “fibrosarcoma-like lipomatous neoplasm” (FLLN), a rare, indolent adipocytic neoplasm considered by some to form part of the spectrum of atypical spindle cell and pleomorphic lipomatous tumor. We compared the morphologic, immunohistochemical, and genetic features of 23 tumors previously classified as LLT (n = 17) and FLLN (n = 6). The 23 tumors occurred in 13 women and 10 men (mean age, 42 years; range, 17 to 80 years). Eighteen (78%) cases arose in the inguinogenital region, whereas 5 tumors (22%) involved noninguinogenital soft tissue, including the flank (n = 1), shoulder (n = 1), foot (n = 1), forearm (n = 1), and chest wall (n = 1). Microscopically, the tumors were lobulated and septated, with variably collagenized fibromyxoid stroma, prominent thin-walled vessels, scattered univacuolated or bivacuolated lipoblasts, and a minor component of mature adipose tissue. Using immunohistochemistry, 5 tumors (42%) showed complete RB1 loss, with partial loss in 7 cases (58%). RNA sequencing, chromosomal microarray, and DNA next-generation sequencing study results were negative for significant alterations. There were no clinical, morphologic, immunohistochemical, or molecular genetic differences between cases previously classified as LLT or FLLN. Clinical follow-up (11 patients [48%]; range, 2-276 months; mean, 48.2 months) showed all patients were alive without disease, and only one patient had experienced a single local recurrence. We conclude that LLT and FLLN represent the same entity, for which “LLT” seems most appropriate. LLT may occur in either sex and any superficial soft tissue location. Careful morphologic study and appropriate ancillary testing should allow for the distinction of LLT from its potential mimics.

AI-based identification of FGFR3 mutation status from routine histology slides of muscle-invasive bladder cancer.

e16580 Background: Gain of function mutations of the FGFR3 gene have been reported to be important driver mutations in a subset of muscle-invasive bladder urothelial cancer (MIBC). Subsequently, gene specific kinase inhibitors (e.g., erdafitinib) have been developed to target FGFR3 mutant metastasized MIBC with promising clinical activity. FGFR3 mutational status testing is required for erdafitinib treatment, but FGFR3 mutations are rare in metastatic MIBC (10-15%). Thus, cheap and fast pre-screening tools such as artificial intelligence (AI) based image classifiers could help to reduce turnover times of FGFR3 mutational testing and save costs arising from universal mutational testing. Herein, we propose an AI-based approach to identify MIBC FGFR3 mutated patients on routine histological slides. Methods: Slides from 612 patients with MIBC from two different sources (CCC-EMN Erlangen cohort n = 239, mutant = 20; TCGA-BLCA n = 373, mutant = 50) were used. The CCC-EMN cohort was used as a discovery set while TCGA-BLCA was used as an independent validation set. A two-step AI model was used to 1) extract features from each slide and 2) predict FGFR3 status from these features. The AUC, sensitivity and specificity were used as metrics to assess the performance of our model. Most predictive regions of FGFR3 mutation were reviewed by an expert pathologist. Results: The model reached an AUC/Sensitivity/Specificity of 0.82 [0.76-0.87] / 0.90 [0.82-0.97] / 0.57 [0.53-0.62] on TCGA-BLCA, substantially improving upon results previously reported on the same cohort (Loeffler et al. 2021: AUC = 0.70). Most predictive regions of FGFR3 mutation revealed monomorphous conventional urothelial tumor morphology and low desmoplastic tumor stroma content, while least predictive regions contained pleomorphic tumor morphology and high amounts of desmoplastic tumor content. Conclusions: By ruling out 57% of MIBC FGFR3 wild type tumors with high sensitivity, our model is the first to reach valuable performance for clinical use. Consequently, this study paves the way for the development of FGFR3 pre-screening tools to ease the management of patients with MIBC.

EPITHELIOID GLIOBLASTOMA OF BRAIN: A RARE CASE REPORT WITH REVIEW OF LITERATURE

A 52 year old female presented with complains of headache, dizziness and vomiting. Her MRI revealed a heterogenously enhancing tumor in right temporal lobe. She underwent gross total resection followed by chemoradiotherapy, but later succumbed to her illness. Histopathology showed highly pleomorphic tumor cells with eosinophillic cytoplasm and pleomorphic vesicular nuclei. A diagnosis of Epithelioid Glioblastoma was made. Epithelioid Glioblastoma is a rare pseudoepithelial form of glioblastoma. It usually presents in younger age group, is more malignant, difcult to differentiate from usual GBMs on radiology and needs aggressive management. No streamlined protocols exist for their diagnosis and treatment. The following communication discusses its epidemiology, pathology, diagnosis and management.

Establishment and characterization of urothelial carcinoma cell lines with and without BRAF mutation (V595E) in dogs

Each 5 urothelial carcinoma (UC) cell lines with and without the v-Raf murine sarcoma virus oncogene homolog B (BRAF) gene mutation (V595E) were established and examined V595E-related tumorigenic characteristics in dogs. No typical morphological features were observed in cloned cells with and without V595E. The cell proliferation of both cloned cells showed logarithmic growth curve and those doubling time were 24.9 ± 4.1 h in V595E ( +) and 29.3 ± 11.3 h in V595E ( −). On the growth curve of xenotransplanted tumor in severe combined immunodeficiency mice, 3 out of 5 V595E ( +) and 2 out of 5 V595E ( −) cloned cells revealed gradually and remarkably increasing curve, indicating clearly tumorigenicity. The xenotransplanted tumors with V595E ( +) showed typical features of UC, such as solid proliferation of pleomorphic tumor cells, formation of papillary structure, and glandular structure. Additionally, various vascular formation was observed, probably indicating an advanced growth phase of UC. In mitogen-activated protein kinase (MAPK) signaling pathway, cytoplasmic phosphorylated-BRAF (pBRAF) and cytoplasmic and nuclear phosphorylated-ERK1/2 (pERK1/2) were detected in all 4 tumors with V595E ( +), whereas only cytoplasmic and nuclear pERK1/2 was detected in tumors with V595E ( −). Since V595E can directly activate MAPK signaling pathway, coincidence of V595E with pBRAF (phosphor Thr598/Ser601) indicates acquired resistance to BRAF inhibitors. These established UC cell lines, especially V595E ( +) cell lines, are useful tool for understanding pathophysiological states and controlling therapeutic manners of UC in dogs.