Giant Cell Variant Research Articles

“De novo replication repair deficient glioblastoma, IDH-wildtype” is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade

Glioblastoma is a clinically and molecularly heterogeneous disease, and new predictive biomarkers are needed to identify those patients most likely to respond to specific treatments. Through prospective genomic profiling of 459 consecutive primary treatment-naïve IDH-wildtype glioblastomas in adults, we identified a unique subgroup (2%, 9/459) defined by somatic hypermutation and DNA replication repair deficiency due to biallelic inactivation of a canonical mismatch repair gene. The deleterious mutations in mismatch repair genes were often present in the germline in the heterozygous state with somatic inactivation of the remaining allele, consistent with glioblastomas arising due to underlying Lynch syndrome. A subset of tumors had accompanying proofreading domain mutations in the DNA polymerase POLE and resultant “ultrahypermutation”. The median age at diagnosis was 50 years (range 27–78), compared with 63 years for the other 450 patients with conventional glioblastoma (p < 0.01). All tumors had histologic features of the giant cell variant of glioblastoma. They lacked EGFR amplification, lacked combined trisomy of chromosome 7 plus monosomy of chromosome 10, and only rarely had TERT promoter mutation or CDKN2A homozygous deletion, which are hallmarks of conventional IDH-wildtype glioblastoma. Instead, they harbored frequent inactivating mutations in TP53, NF1, PTEN, ATRX, and SETD2 and recurrent activating mutations in PDGFRA. DNA methylation profiling revealed they did not align with known reference adult glioblastoma methylation classes, but instead had unique globally hypomethylated epigenomes and mostly classified as “Diffuse pediatric-type high grade glioma, RTK1 subtype, subclass A”. Five patients were treated with immune checkpoint blockade, four of whom survived greater than 3 years. The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that “De novo replication repair deficient glioblastoma, IDH-wildtype” represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

Descriptive Statistics for Patients with Glioblastoma Associated with Germline Mismatch Repair Gene Mutation

<h3>Purpose/Objective(s)</h3> Hereditary Nonpolyposis Colorectal Cancer (HNPCC), also known as Lynch Syndrome, is a genetic mismatch repair mutation associated with increased risk for development of glioblastoma (GBM). There is a paucity of data describing the clinical outcomes of GBM patients with HNPCC. We aim to describe tumor characteristics, treatment patterns, and outcomes. <h3>Materials/Methods</h3> IRB approved retrospective review of consecutive patients with a diagnosis of both HNPCC and GBM at a single institution. <h3>Results</h3> Nine patients with a diagnosis of HNPCC and GBM were treated at a single institution from 2001-2022. Six patients were male. Median age at GBM diagnosis was 61 (range 21-84). Median follow up from the time of GBM diagnosis was 7.83 months. Eight patients had prior malignancies: n=7 with colon adenocarcinoma, n=1 with Burkitt lymphoma. Two patients had active synchronous cancers with GBM. The most common presenting symptoms were facial droop (n=3) and cognitive changes (n=2). Others include headache, gait change, visual field defect, and seizures with n=1 each. All patients underwent surgery: n=2 gross total resection, n=4 subtotal resection, and n=3 biopsy alone. There were 3 temporal lobe, 3 parietal lobe, 2 frontal lobe, and 1 frontoparietal lobe tumors. Two patients had multifocal disease at diagnosis. One patient had a giant cell variant GBM. Seven patients had MSH6 mutations and 2 had MSH2 mutations. Two patients progressed rapidly after surgery and were unable to receive RT. Seven patients received adjuvant radiation therapy (RT): n=5 received concurrent TMZ- 1 with concurrent bevacizumab, 5-fluorouracil, and leucovorin due to synchronous metastatic colon cancer, 1 received no chemotherapy. The most common dose and fractionation schedules were 60 Gy in 30 fractions (fx) (n=3), 40.05 Gy in 15 fx (n=3), and n=1 received 30 Gy in 10 fx due to poor performance status and large tumor volume. One patient received proton therapy for active MS, n=8 received IMRT. Two patients initiated tumor treating fields following RT completion. The median time to progression after RT was 3.35 months, and all progressed within the radiation field. Median survival from diagnosis was 6.5 months (range 1.2-15.5). No patients received immune checkpoint inhibitors. One patient was alive at the time of data collection. Seven died due to GBM progression, and n=1 died from progression of a synchronous malignancy. <h3>Conclusion</h3> In this small series, patients with mismatch repair mutation associated glioblastoma had especially poor outcomes and a rapidly progressive disease course.

Chronicles of A.I. Pospelov Moscow Dermatovenerology and Cosmetology Society (MSDC was founded on October 4, 1891) Bulletin of the MSDC № 1146

On February 15, 2022, the 1146th meeting of the Moscow Society of Dermatovenereologists and Cosmetologists named after A.I. Pospelov took place.&#x0D; The meeting was held in a remote format. There were 120 participants in total. Accepted as a member of MSDC 1 person.&#x0D; Three clinical clinical observations are presented. The first of them is a case of giant-cell variant of annular granuloma with extensive skin lesions. Annular granuloma is a benign dermatosis of unclear etiology, prone to spontaneous resolution; it occurs as a reaction to ultraviolet radiation against the background of lymphoproliferative or autoimmune diseases, sarcoidosis, chronic lung diseases, prostate cancer. In the presented case, the clinical diagnosis was confirmed by histological examination.&#x0D; The second presentation was devoted to livedoid vasculopathy with a tendency to thrombotic complications. This is a relatively rare disease that is excluded from the group of vasculitis due to one distinctive feature ― a pronounced tendency to thrombosis in the absence of indications of the primary nature of inflammation. In therapy, in addition to medications, the appointment of vitamins is mandatory.&#x0D; The third observation concerned Merkels carcinoma, one of the relatively rare but extremely aggressive most malignant forms of skin cancer. With epithelial and neuroendocrine differentiation, which is superior to melanoma in terms of aggressiveness of the course and tendency to metastasis. Due to the rare occurrence of the tumor, diagnostic errors are frequent. Diagnosis requires histological and immunohistochemical examination. Any inflamed atheroma or synovial cyst that recurs after surgical treatment should be alarming.&#x0D; Scientific reports were heard on the biological therapy of psoriasis, a chronic systemic immunoassociated disease of a multifactorial nature with a hereditary predisposition characterized by the formation of inflammatory papules and plaques, often with joint damage (arthropathy), accelerated proliferation of epidermocytes and a violation of their differentiation, an imbalance between pro-inflammatory and anti-inflammatory cytokines and chemokines. And the second scientific report contained information about modern approaches to the treatment of acantholytic pemphigus.

Osteoclastic giant cell variant of urothelial carcinoma in a COVID- positive patient: A rare variant in an unusual circumstances

Bladder carcinomas have a great propensity for divergent differentiation with more that 90% being Transitional cell carcinoma. Several histological variants have been have described so far; they are not only morphologically unique but also have significant prognostic and therapeutic differences making their timely identification of paramount importance. Osteoclastic giant cell variant of urothelial carcinoma is very rare type with controversial management. Studies from China have documented higher incidence and severity of illness in COVID-19 positive cancer patients. We report an unusual case of Osteoclastic giant cell variant of urothelial carcinoma in a 63 yrs old male patient associated with simultaneous COVID-19 infection.

Giant cell ependymoma: Cytology of a rare entity with unusual presentation

Giant cell ependymoma (GCE) is a slow-growing tumor that accounts for 9–13% of all ependymoma and occurs preferably at conus medullaris, cauda equina, and filum terminate. Squash cytology is a fast, simple, and reliable technique for intraoperative diagnosis. We present a case of GCE arising at the L5-S2 level and suprasellar region in a 17-year-old male who initially presented with low backache followed by headache and double vision. Intraoperative squash smears of the lumbosacral lesion were suggestive of high-grade glioma. Histomorphological and immunohistochemical profile favors the diagnosis of giant cell variant of myxopapillary ependymoma. He received craniospinal irradiation followed by a boost to the sellar-suprasellar and lumbosacral region through IGMT. After sometime, he developed papilledema and decreased vision, the suprasellar lesion was decompressed which on histopathology revealed similar features. GCE remains a diagnostic challenge on intraoperative squash smears due to its rarity. It has a good prognosis with a 5-year survival of 98.4% after total resection; however, our patient succumbed to illness due to post-operative residual lumbosacral mass and effects of the suprasellar lesion.

Giant Cell Variant of Glioblastoma Multiforme: Report of a Rare Variant in a Child

Malignant glial tumors are rare in children. Giant cell variant is a rare subtype of glioblastoma, accounting for about 0.8% of brain tumors and 5% of glioblastoma tumors. Giant cell glioblastoma is a male predominant tumor in children and adults. Due to the low prevalence of this variant, available information is limited. An 11-year-old female child was referred with a chief complaint of a progressive persistent headache. MRI showed a well-defined cystic lesion with a solid mural component in the right parietal lobe with a compression effect on the ipsilateral ventricular system. Surgery was done. After the pathologist reported glioblastoma multiforme, a giant cell variant, the patient received 30 sessions of radiation therapy. The patient was readmitted 18 months later with a headache, and the pathologist confirmed the recurrence of the tumor. Based on radiology, the giant cell glioblastoma cannot be distinguished from the common subtype glioblastoma. The pathologists must be aware of this entity, and histologic differential diagnoses are warranted for diagnostic, prognostic, and therapeutic purposes.

Diagnostic value of urine cytology in detecting histologic variants of urothelial carcinomas in the urinary bladder: Cytopathologic correlation of 72 cases.

Precise identification of histologic variants in urothelial carcinoma (UC) is important because some histologic types have a poor prognosis and clinical management varies. Urine cytology is used for bladder cancer screening, but the cytomorphologic features of histologic variants have not been well described. In the current study, we evaluate the effectiveness of urine cytology in detecting histologic variants of UC in the urinary bladder. Seventy-two urine cytology specimens from patients diagnosed with high-grade UCs by radical cystectomy were retrospectively reviewed and correlated with histopathologic findings of subsequent radical cystectomy specimens. Of 72 total cases, 24 (33%) cases showed six histologic variants in corresponding surgical specimens, including squamous differentiation (13 cases), plasmacytoid variant (3 cases), micropapillary variant (3 cases), sarcomatoid variant (3 cases), giant cell variant (1 case), and glandular differentiation (1 case). Histopathology and cytomorphology were well correlated in 13 cases (54%), with squamous differentiation in 11 of 13 cases (85%), micropapillary features in 1 out of 3 cases (33%), and spindle cell/sarcomatoid features in 1 of 3 cases (33%). Furthermore, mucosal involvement by histologic variants, not amount of histologic variant, was related to high concordance rates between cytology and histology diagnosis. The morphologic features of some histologic variants of high-grade UCs, such as squamous differentiation, micropapillary variant, and sarcomatoid variant, are partially reflected on urine cytology. In addition, mucosal involvement by histologic variants was associated with a higher detection rate of histologic variants in urine cytology.

Role of cytology in differentiating anaplastic thyroid carcinoma with osteoclast like giant cells from giant cell variant of medullary thyroid carcinoma

Anaplastic thyroid carcinoma (ATC) is a highly aggressive tumor and constitutes 2%–5% of all thyroid carcinomas. The cytological diagnosis of osteoclast giant cell variant of ATC is extremely rare, and only a few cases have been described in literature. A 67 - year-old female underwent fine-needle aspiration cytology from the thyroid nodule. Smears revealed hypercellular aspirate comprising of clusters and singly scattered atypical cells with few interspersed multinucleated tumor cells. Cytomorphological differential diagnosis of giant cell/pleomorphic variant of medullary carcinoma and anaplastic carcinoma was offered. Histomorphological features on cell block assisted with immunohistochemistry confirmed the diagnosis of ATC with osteoclastic-like giant cells. Computed tomography-guided right lung lesion aspirate was reported as metastasis of high-grade poorly differentiated carcinoma. The patient was managed with cisplatin-based chemotherapy. This case highlights the importance of cytological diagnosis of ATC to guide the treatment modality of chemotherapy thus avoiding surgery, especially in old moribund patient with lung metastasis.

Characterization of five newly derived canine osteosarcoma cell lines

BackgroundCanine and human osteosarcomas (OS) are notably similar and have a high rate of metastasis. There is a poor understanding of the tumor development process, predisposing causes, and varying levels of aggression among different cell lines. By characterizing newly developed canine osteosarcoma cell lines, treatments for people and pets can be developed. Of the seven subtypes of OS, three are represented in this group: osteoblastic (the most common), fibroblastic, and giant cell variant. To our knowledge, there are no other giant cell variant canine OS cell lines in the published literature and only one canine fibroblastic osteosarcoma cell line. Understanding the differences between the histologic subtypes in dogs will help to guide comparative research.ResultsAlkaline phosphatase expression was ubiquitous in all cell lines tested and invasiveness was variable between the cell lines tested. Invasiveness and oxidative damage were not correlated with in vivo growth rates, where TOT grew the fastest and had the higher percentage of mice with metastatic lesions. TOL was determined to be the most chemo-resistant during cisplatin chemotherapy while TOM was the most chemo-sensitive.ConclusionsFurther comparisons and studies using these cell lines may identify a variety of characteristics valuable for understanding the disease process and developing treatments for osteosarcoma in both species.Some of this data was presented as a poster by KMF at the August 5th, 2017 National Veterinary Scholars Program in Bethesda, MA.Characterization of 5 newly generated canine osteosarcoma cell lines.Kelli Franks, Tasha Miller, Heather Wilson-Robles.

Differing characteristics of cartilaginous lesions\xa0of the larynx

IntroductionThe tissues of the laryngeal region only rarely harbor primary cartilaginous lesions, and squamous cell carcinoma remains the most frequently encountered malignant tumor in this area.Materials and MethodsWe reviewed the salient histological features of cartilaginous laryngeal lesions to provide differential diagnostics and guidelines for distinguishing the benign from the malignant ones.ResultsCartilaginous neoplasms of the larynx include chondroma and chondrosarcoma. Among the overarching group of all forms of laryngeal sarcoma, chondrosarcoma forms the most common entity in the larynx, followed by rhabdomyosarcoma. Cartilaginous tumors comprise about 0.1%–1% of all laryngeal neoplasms with chondrosarcomas being more frequently encountered than chondromas. Several neoplasms earlier reported as giant-cell tumors of the larynx would most likely, using current terminology, be classified as cases of undifferentiated pleomorphic sarcoma (previously known as malignant fibrous histiocytoma, giant-cell variant) or aneurysmal bone cyst.ConclusionWhen true laryngeal sarcomas do exist, they may prove to be challenging lesions both for the pathologist and the treating clinician. The diagnostic problems are mainly a result of the infrequent exposure of clinicians and diagnosticians to these lesions.

Giant malignant fibrous histiocytoma of the testis.

We present a case of malignant fibrous histiocytoma of the testis in a 59 year- old male who admitted to our hospital with left testicular painless mass presenting for two months. A scrotal ultrasound examination and magnetic resonance imaging revealed a 9 cm left testicular solid mass. Serum tumor markers were unremarkable. The patient underwent left radical orchiectomy. Histopathologic diagnosis was giant cell variant of malignant fibrous histiocytoma which composed of varying amounts of a mixture of spindled, rounded and osteoclastic type giant cells. Hemorrhagic and necrotic areas were seen between tumor nodules. In immunohystochemical staining, vimentin, CD68 were positive and SMA was focally positive. The patient then received adjuvant chemoterapy and currently, he has no sign of recurrence.

GIANT CELL CARCINOMA OF THE RENAL PELVIS AND URETER WITH GIANT HYDRONEPHROSIS; A CASE REPORT

A 78-year-old woman presented with macroscopic hematuria. We diagnosed giant hydronephrosis with a left ureteral stone and multiple renal pelvic carcinoma cT3N0M0 tumors.Open nephroureterectomy proceeded via a peritoneal approach, and 8,600 mL of urine were collected from the renal pelvis. The pelvic carcinoma was histologically confirmed as a rare giant cell variant with high malignant potential. The same variant was found in the upper ureter where a 15-mm stone had lodged. We considered that this was due to rapid progression of the renal pelvic giant cell carcinoma and hydronephrosis during the month before surgery.Multiple lung and bone metastases occurred after three courses of gemcitabine/cisplatin combination chemotherapy as postoperative adjuvant therapy. Therefore, radiotherapy for bone metastasis and gemcitabine/paclitaxel combination chemotherapy were performed concurrently.

Morphologic Variants of Epithelial and Neuroendocrine Tumors of the Prostate. The Pathologist's Point of View

Abstract More than 95% of all carcinomas of the prostate are referred to as acinar, microacinar, usual, or conventional type. A minority have been classified as variants. Variants can vary in histologic appearance and divergent differentiation compared with usual acinar adenocarcinoma. Some variants constitute different types of carcinoma and are not adenocarcinomas. Variants that represent a challenge to diagnose include the deceptively benign-looking atrophic, pseudohyperplastic, microcystic, and foamy gland variants. The signet ring-like, pleomorphic giant cell, and sarcomatoid variants have worse prognosis than usual acinar adenocarcinoma. Some variants can occur after therapy, such endocrine and radiation therapy: squamous neoplasms, neuroendocrine tumors, sarcomatoid carcinoma (ie, carcinosarcoma), and pleomorphic giant cell variant. Neuroendocrine prostate cancer is an aggressive variant of prostate cancer that often arises in later stages of castration-resistant prostate cancer.

Aneurysmal bone cyst of the talus

Aneurysmal bone cysts (ABCs) localized in the talus are extremely rare. ABC or giant cell variants when located in the talus may be difficult to differentiate and tend to exhibit a less aggressive biological behavior with a more favorable prognosis than the more classical proximal lesions. Talectomy is not indicated as the primary treatment, curettage with or without bone graft has a high success rate, and cryosurgery should be reserved for a recurrent lesion.

Prostate Cancer Heterogeneous High-Metastatic Multi-Organ-Colonizing Chemo-Resistant Variants Selected by Serial Metastatic Passage in Nude Mice Are Highly Enriched for Multinucleate Giant Cells.

In order to further understand the role of tumor heterogeneity in metastasis and chemo-resistance, high metastatic PC-3 human prostate cancer variants were selected by injecting parental PC-3 cells, expressing green fluorescent protein (GFP) in the footpad of nude mice, which then metastasize to inguinal lymph nodes. The PC-3-GFP cells which metastasized to the inguinal lymph nodes were collected and were re-injected to the footpad. After 6 such cycles, the PC-3-GFP cells collected from inguinal lymph nodes (PC-3-GFP-LN) were again injected to the footpad. PC-3-GFP-LN showed 100% metastasis to major lymph nodes (popliteal, inguinal, axillary, and cervical), and 100% metastasis to bone and lung. The percent of giant cell variants was enriched in PC-3-GFP-LN-6 compared to parental cells and increased with each cycle of selection, which in turn had increased metastasis. PC-3-GFP-LN-6 cells were resistant to 5-fluorouracil, doxorubicin and cisplatinum, compared to parental PC-3. However, PC-3-GFP-LN-6 was sensitive to the traditional Chinese medicine (TCM) herbal mixture LQ, similar to the parental cells. These results suggest that PC-3 tumors are heterogenous and that subpopulations of highly metastatic, drug-resistant cells can be step-wise selected using a mouse model of tumor progression.

Leiomyosarcoma with prominent osteoclast-like giant cells: a clinicopathologic analysis of 7 cases and review of literature

To study the clinicopathologic features of leiomyosarcoma with prominent osteoclast-like giant cells. The clinical and pathologic features of 7 cases of leiomyosarcoma with prominent osteoclast-like giant cells were analyzed. Immunohistochemical and ultrastructural studies were performed. The literature was reviewed. All cases occurred in adults, with a mean age of 63 years. There was no significant sex predilection (male-to-female ratio = 4:3). The tumor involved subcutaneous soft tissue of thigh (number = 2), left back (number = 1), retroperitoneum (number = 1), small intestine (number = 1), breast (number = 1) and uterus (number = 1). Histologic examination showed that the tumor was composed of relatively uniform spindly cells arranged in interlacing fascicles. The hallmark was the presence of prominent osteoclast-like giant cells, either intimately admixed with the spindly cells (number = 6) or forming giant cell tumor-like nodules (number = 1). Immunohistochemically, the spindly cells expressed smooth muscle actin, muscle-specific actin, desmin and h-caldesmon in various degrees, whereas the osteoclast-like giant cells expressed CD68. Ultrastructural study showed smooth muscle differentiation in the spindly cells and histiocytic differentiation in the osteoclast-like giant cells. Follow-up data were available in 6 cases. There were local recurrences and/or metastases in all the 6 patients. Three patients were alive with unresectable or recurrent/metastatic disease and two patients died of the disease. Leiomyosarcoma with prominent osteoclast-like giant cells is a rare variant of leiomyosarcoma which should be distinguished from the so-called giant cell variant of malignant fibrous histiocytoma. The osteoclast-like giant cells are of histiocytic differentiation. Surgical resection remains the mainstay of management of this high-grade sarcoma.

Cerebellar giant cell glioblastoma multiforme in an adult

ABSTRACTCerebellar glioblastoma multiforme (GBM) is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

BRAF-V600E mutation in pediatric and adult glioblastoma

With the recent identification of the BRAF rearrangement/duplication in pediatric pilocytic astrocytomas (PA),1–3 there has been renewed interest in the contribution of the BRAF geneto braintumorigenesis. While the signature KIAA1549:BRAF fusion represents a common alteration in PA, activating mutations in the BRAF kinase gene (V600E) are more commonly observed in other glioma histological subtypes and malignancy grades. In this regard, we and others have previously found relatively few BRAF-V600E mutations in PA (<10% cases),1–4 whereas BRAF-V600E mutations are frequently identified in pleomorphic xanthoastrocytomas (WHO grades II and III; 50%–65% cases),5–8 gangliogliomas (20%–75% cases),6–10 and to a lesser frequency in diffuse gliomas,6,11 dysembryoplastic neuroepithelial tumors,10 desmoplastic infantile astrocytoma/ganglioglioma,10 and atypical teratoid/rhabdoid tumors arising in a background of either ganglioglioma or pleomorphic xanthoastrocytoma.7 In contrast, approximately 5% of adult high-grade gliomas, as well as a distinctive subset of adult diffuse low-grade gliomas, harbor BRAF-V600E mutations.6,11,12 Since most BRAF-V600E-positive glial neoplasms are encountered in young persons, we investigated the frequency of this mutation in pediatric high-grade gliomas. Immunohistochemical analyses were conducted using a BRAF-V600E-specific antibody on tissue microarrays containing pediatric gliomas from 2 different institutions (Washington University and University of California, San Francisco) (clone VE1; Spring Bioscience; dilution 1:100). Using this method, none of the low-grade pediatric gliomas (n = 75; 67 WHO grade I PAs, 6 WHO grade II astrocytomas, 1 WHO grade II oligodendroglioma, and 1 WHO grade II mixed oligoastrocytoma) harbored a BRAF-V600E mutation. Of note, 23 of the PA tumors (34%) arose outside of the cerebellum. In contrast, 3 of 11 WHO grade III anaplastic astrocytomas (27%) and 3 of 25 (12%) WHO grade IV glioblastomas (GBMs) were BRAF-V600E immunoreactive. All of the BRAF-V600E-immunopositive glioblastomas were primary GBM. To determine whether the low frequency of BRAF-V600E mutation observed in pediatric GBM was comparable to that observed in their adult counterparts, we examined 39 adult GBMs by immunohistochemistry. Three of these adult GBM tumors (7.7%) were BRAF-V600E immunoreactive: Two of these were giant-cell variants, and the expression appeared to be limited to the “monstrous cells”. Similar to their pediatric counterparts, all of these BRAF-V600E-immunopositive tumors were primary glioblastoma. Of note, these BRAF mutant tumors were generally found in younger patients (35–43 years with a mean age of 39 years compared to 27–79 years with a median age of 55.4 years for BRAF-V600E-immunonegative tumors; P = .0495). None of the BRAF-V600E-immunopositive tumors harbored the isocitrate dehydrogenase-1 (IDH1) R132H mutation. In addition, 2 of these tumors arose in women, despite a slight overall male preponderance in our series (25 males:14 females). The results of our series are comparable to the documented frequencies reported in the literature for adults (9/152 cases; 5.9%).4,6,12–14 While there were few BRAF-V600E-positive adult GBMs in our series, one of these patients is currently alive at 4.5 years. This finding is intriguing because at least 2 of the previously reported adult GBMs also exhibited prolonged survival (3 years).11,12 It is possible that BRAF-V600E mutations are either encountered in rarer, more favorable subtypes of GBM or that they confer different biological properties to these glial neoplasms, translating to improved clinical outcomes. In this regard, BRAF-V600E mutations have been reported to occur in over 50% of epithelioid GBM.12 This uncommon histologic variant appears to be more common in young adults,12 and is equally represented in males and females in one series as opposed to the male predominance typically seen in rhabdoid GBM.15 However, whether or not adult patients carrying BRAF-V600E mutations have a survival advantage remains to be established using additional patient cohorts. Coupled with encouraging therapeutic studies demonstrating that BRAF and MEK inhibitors exhibit therapeutic efficacy in BRAF-V600E; Ink4a-deficient murine malignant glioma preclinical studies,16 the potential preselection of patients with GBM by BRAF-V600E mutation for BRAF/MEK inhibitor treatment may prove beneficial in combination with other therapies.

Soft tissue solitary fibrous tumor. Imaging findings in a series of nine cases

Few articles have been published regarding the imaging characteristics of soft tissue solitary fibrous tumors (SFT). The aim of this study is to describe the radiological features in a series of nine patients and to compare these results with pathological and clinical outcome. Nine cases of soft tissue SFT, confirmed by an experienced tumor pathologist, were studied with imaging techniques (US and MRI). Tumor location, size, morphology, local invasion, vascularity, MRI signal intensities, and dynamic contrast-enhancement patterns were recorded. Tumors were subclassified into cellular, fibrous, and giant cell forms histologically. The most common findings were a well-defined, polylobulated mass that tended to displace adjacent structures. The extremities were the most frequent site of presentation. The tumors showed high vascularity in all imaging studies. The radiological features that correlated better with malignant criteria were tumor size, heterogeneous signal intensity, and heterogeneous uptake of contrast on MRI. On dynamic contrast-enhanced (DCE) sequences, three tumors showed a biphasic curve (type IV) and one a progressive uptake curve (type II). The latter recurred twice after extensive local surgery and was classified as a giant cell variant. In this study a retrospective review of nine new cases of soft tissue SFT was carried out. The presence of a large solid, highly vascularized mass with a prominent vascular pedicle that displaces adjacent structures may suggest the diagnosis of an SFT. DCE sequences might help identify those tumors with worse clinical outcome, but a study with a larger series of patients is needed.

Atypical fibroxanthoma in a woman and literature review

Atypical fibroxanthoma (AFX) is a superficial variant of pleomorphic malignant fibrous histiocytoma. AFX an rare tumor of skin seen mainly in the head and neck region of elderly patients. Clinically, it can be difficult to differentiate from other tumors without histopathological examination. It may clinically resemble squamous cell carcinoma, malignant melanoma, or pyogenic granuloma. The histologic differential diagnosis primarily includes peripheral giant cell granuloma, spindle cell squamous carcinoma, and spindle cell melanoma. Clinical findings and immunohistochemical studies are often needed to establish the diagnosis. The prognosis is generally excellent, although there are rare cases of metastatic disease. The case was 77-year-old female patient. She had a 1.5 cm red-brown bulging lesion on her left cheek that sometimes can bleed for 4 years. As clinically piyogenic granuloma was considered. Excisional biopsi was performed. There was not any lymphadenopathy in her head neck region. Microscopically, the case was interpreted as AFX. The histologic appearance of this lesion was reminiscent of the peripheral giant cell granuloma and giant cell variant of malignant fibrous histiocytoma, also termed malignant giant cell tumor of soft parts. Particularly skin lesions, clinicopathologic correlation is important. Appropriately as can be much easier to diagnose.