Spindle Cell Research Articles

Appendiceal neurofibroma after resection of multiple gastrointestinal stromal tumors of the small intestine in a patient with neurofibromatosis type 1: a case report.

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is an autosomal dominant disorder that can affect multiple organs. Although gastrointestinal manifestations, such as neurofibromas and gastrointestinal stromal tumors (GISTs), can occur, appendiceal neurofibromas are extremely rare, with no documented cases of their occurrence following other gastrointestinal lesions. Herein, we report a case of an appendiceal neurofibroma following the resection of multiple small intestinal GISTs. A 68-year-old man with NF1 presented with melena and was diagnosed with anemia due to bleeding from multiple small intestinal GISTs. Laparoscopic three partial resection of the small intestine was performed to control the bleeding. Histopathologic examination revealed the proliferation of spindle cells that are positive for c-kit and Discovered on GIST-1, confirming the diagnosis of GIST. Two years later, a follow-up computed tomography (CT) scan revealed a progressively enlarging mass in the appendix with suspected invasion into the small intestine. Positron emission tomography/CT showed fludeoxyglucose accumulation in the tumor. Therefore, considering the possibility of malignancy, laparoscopic ileocecal resection with lymph node dissection was performed. Postoperatively, melena was observed, but the anemia did not progress and improved with fasting and hemostatic therapy. The patient was eventually discharged on postoperative day 8. Histopathologic examination revealed spindle cell proliferation with positivity for S-100, confirming the diagnosis of neurofibroma. Patients with NF1 can develop a variety of gastrointestinal lesions. Appendiceal neurofibroma can be difficult to diagnose preoperatively and differentiate from malignancy. Hence, surgical resection should be considered.

BCOR-ITD Rearranged Sarcoma in the Mandible of a 5-Year-Old Child: A Case Report Highlighting Diagnostic Distinction From Odontogenic Fibromyxoma.

The 5th edition of the World Health Organization (WHO) classification of soft tissue and bone has recognized three distinct groups among Ewing-like sarcomas, namely, CIC-rearranged sarcoma, sarcomas with BCOR genetic alterations, and round cell sarcomas with EWSR1:: non-ETS fusions. Sarcomas with BCOR genetic alterations are a distinct clinicopathological group of high-grade tumors, representing 5% of small round cell tumors. BCOR-ITD rearranged tumors commonly manifest as spindle cell sarcomas and many of them display low cellularity with monomorphous cell morphology and myxoid background resembling benign fibroblastic tumors. We present an intriguing case report of a 5-year-old boy diagnosed with a moderately cellular mandibular spindle cell tumor exhibiting BCOR-ITD rearrangement which was initially misdiagnosed as an odontogenic fibromyxoma. This case report illustrates the histological and immunophenotypic findings of BCOR-ITD rearranged sarcoma, requiring a comprehensive immunohistochemical panel and additional molecular tests for accurate diagnosis.

Abstract 4147632: Unusually Expeditious Expansion of an Atrial Myxoma

Description of the Case Report: A 44-year-old female with a past medical history of unspecified skin cancer presented with exertional dyspnea for 1 day before admission and syncope 7 months before admission. Physical exam was noted for soft low low-pitched diastolic murmur at the cardiac apex, not appreciated on prior exam. Echocardiography revealed a 3.3x4.7 cm pedunculated, homogenous mass in the left atrium obstructing the mitral valve. Serum BNP was measured as 326. An echocardiogram from less than 29 months prior was reviewed and showed no mass in the left atrium. The patient underwent successful surgical resection of the mass. The mass measured approximately 7x6x2 cm. Histologic analysis reported a proliferation of myxoid stroma with cytologically bland spindle cells positive for calretinin, compatible with cardiac myxoma. Following the surgery, the patient experienced resolution of symptoms. Discussion: Atrial myxomas are the most common primary cardiac tumors. They present as mitral valve obstruction, mitral valve regurgitation, arrhythmias, or systemic thromboembolism. They are exceedingly rare with an incidence of 0.5 to 1 case per million individuals annually and typically resected immediately. Therefore, instances with well-documented growth rates are uncommon. In this case, we present an unusually fast-growing myxoma in a woman with shortness of breath and syncope. The reported growth rate of atrial myxomas ranges from 1.3 to 6.9 mm a month. Our patient had a negative echocardiogram less than 2.5 years before her presentation, followed by the development of a 7 x 6 x 2 cm mass. Since the onset is unknown, the precise growth rate of our patient's tumor is unknown but was at least 24 mm/month. It is important to consider myxoma in the differential diagnosis of a woman with new onset murmur and syncopal episode. Furthermore, recognizing the potential for rapid expansion is crucial to assessing the risks versus benefits of myxoma section.

Abstract 4131838: Heart’s Deception: A Venous Villain Hiding in the Heart

A 66-year-old male presented with 5 months of worsening left flank and lower back pain. Three weeks prior to this presentation, he was seen at an outside facility where he was found to have a left renal mass that was not further worked up. CT Abdomen and Pelvis showed an enhancing heterogenous lesion at the left superior renal pole, left adrenal gland lesion, and a pulmonary artery filling defect. This defect, along with concern for metastasis, led to a CT chest angiogram that reported small left upper and lower lobe pulmonary emboli. A transthoracic echocardiogram (TTE) was ordered and showed a linear highly mobile mass in the right atrium that was intermittently protruding into the right ventricle and into the main pulmonary artery through the pulmonic valve. There was no visible evidence of tumor extension of the renal mass into the inferior vena cava. Based on this, the highest differential was a clot-in-transit. After collaboration with the pulmonary embolism response team and echo team, the patient underwent aspiration thrombectomy via AngioVac system with transesophageal echocardiography (TEE) guidance. Most of the mass was removed, but there was a residual small portion adherent to the superior vena cava that was not amenable to aspiration. Grossly, the removed mass did not have the classic appearance of thrombus. The specimen was sent to pathology and returned as poorly differentiated carcinoma with spindle cell pattern positive for PAX8, CK7, CD10, pancytokeratin, and vimentin concerning for renal cell carcinoma. Post procedural transthoracic echo found to have new basal septal globular mass with vascularity seen on echo contrast imaging concerning for vascular involvement consistent with myocardial metastatic invasion. Cardiac magnetic resonance imaging could have aided in more precise tissue characterization to differentiate between clot or tumor prior to aspiration thrombectomy. This case demonstrates the significance of a detailed history and physical exam, use of multimodality imaging, and multidisciplinary collaboration to manage a rare cardiac condition.

Clinicopathological Characteristics of Neutrophil-Rich Hepatocellular Carcinoma: An Uncommon Subtype of Primary Liver Cancer.

Introduction. Neutrophil-rich hepatocellular carcinoma (HCC) is an extremely uncommon subtype of HCC with an overall incidence of <1%. Neutrophil-rich HCC shows poor cellular differentiation and sarcomatoid transformation in most patients. There is prominent neutrophilic inflammatory cell infiltration in the tumor. These tumors are associated with poor prognosis, high rate of recurrence, and metastasis. Methods. Herein, we investigated 4 patients with neutrophil-rich HCC reported at our center. Clinical, radiological, and pathological findings were reviewed. Immunophenotypic characterization of the tumors were done. Granulocyte colony-stimulating factor (G-CSF), programmed cell death ligand 1 (PD-L1), and mismatch repair immunostains were performed in all 4 tumors. Results. We report 4 neutrophil-rich HCCs in 3 male patients and one female patient with an age range of 43 to 64 years. Three underwent living donor liver transplantation and one underwent right hepatectomy. Tumor measured 0.5 cm to 12 cm in maximum dimension. Histologically, tumors demonstrated moderate to marked cellular pleomorphism. Spindle cell transformation was noted in 3 tumors. Three tumors showed vascular invasion, and one tumor showed bile duct invasion. Immunopositivity for Hep Par-1, arginase-1, and glypican-3 was present in all tumors. Tumors also expressed stemness markers including KRT19 and EpCAM. Cytoplasmic positivity for G-CSF and immunoexpression of PD-L1 was demonstrated. We also report proficient mismatch repair by immunohistochemistry in all tumors. Conclusion. Neutrophil-rich HCC is an aggressive primary liver cancer which demonstrates stemness-related features. Programmed cell death ligand 1 expression in tumor cells suggests distinct immunogenic features and potential role of anti-PD-L1 therapies in inoperable disease.

Clinicopathological observation and analysis of uveal leiomyoma

Objective: To analyze the clinical and histopathological features of uveal leiomyoma. Methods: A retrospective study was performed on 19 patients with uveal leiomyoma confirmed by histopathological examination in Beijing Tongren Hospital from January 2018 to May 2023. All patients underwent local resection of the tumor. Clinical data of the patients, such as gender, age, clinical manifestations, tumor location, size, and B-scan ultrasound examinations were collected. The pathological morphological characteristics of the tissue (cell type) and the expression of the immune markers, including smooth muscle actin, actin, and neural cell adhesion molecule (CD56), were evaluated. Results: Among the 19 intraocular leiomyoma patients, there were 5 males and 14 females. The average age was (38.9±13.7) years, ranging from 14 to 64 years. The course of the disease ranged from 1 to 36 months with an average of (9.3±8.7) months. The most common clinical manifestation was blurred vision (12/19), followed by decreased vision (4/19), increased IOP (2/19), and visual occlusion (1/19) in patients. The tumor was located in the ciliary body in 10 female and 5 male patients, including 2 patients with the iris involved, and in the choroid in 4 female patients. Two patients with a history of breast fibronenoma had uveal leiomyoma in the ciliary body and the choroid, respectively. One patient with a history of uterine leiomyoma suffered uveal leiomyoma in the ciliary body. B-scan ultrasonography showed that the tumor was a solid and medium-low echoic lesion with a clear boundary in all eyes. We divided these leiomyomas into two histopathological types: spindle cell type (15/19) and round cell type (4/19). Immunohistochemical staining disclosed smooth muscle actin and actin were expressed in all tumor cells (19/19, 100%), and CD56 was positive in 16 of 19 eyes (84.2%). The positive expression rates of estrogen and progesterone were 0/19 and 2/19. During the follow-up of 7 to 71 months after surgery, no tumor metastasis occurred. Only 1 male patient had tumor recurrence. Conclusions: The most common site of uveal leiomyoma is the ciliary body, the major clinical manifestation is blurred vision, and the prognosis is good. Most of the tumors are spindle cell tumors, with myogenic and neurogenic histological characteristics. Although uveal leiomyoma is more frequently found in women of reproductive age, it shows no significant correlation with estrogen and progestational hormones.

An Atypical Case of Pancreatic Cancer with Mesenchymal Differentiation in a Patient with Primary Lung Adenocarcinoma: Insights into Tumor Biology and Novel Therapeutic Pathways

Background: Pancreatic cancer is among the malignancies with the poorest prognosis, largely due to its aggressive nature and resistance to conventional therapies. Case Summary: This report describes the case of a 69-year-old male patient with stage IV primary lung adenocarcinoma presenting with high levels of programmed death-ligand 1 (PD-L1). Simultaneously, abdominal computed tomography (CT) showed a dilated pancreatic duct at the level of the pancreatic head and a hypodense lesion in the uncinate process involving the superior mesenteric artery. Fine-needle aspiration (FNA) of the pancreatic lesions was negative. After three cycles of chemoimmunotherapy, positron emission tomography–computed tomography (PET-CT) showed complete remission of the lung nodules, lymphadenopathy, and pleural thickening, as well as a decrease in the size of the pancreatic lesion. After another six months, a PET-CT scan showed a focal increased uptake in the pancreatic mass in the same location, indicating disease progression. A core biopsy of the pancreatic tumor showed atypical spindle cell morphology with positive staining for vimentin, characteristic of mesenchymal differentiation with no apparent epithelial features. Comprehensive molecular profiling through Caris Molecular Intelligence® revealed four genes with actionable mutations in the pancreatic tissue, including KRAS (p.G12D) and TP53 (p.R175H). These molecular findings suggested the diagnoses of sarcomatoid carcinoma and conventional pancreatic ductal adenocarcinoma with epithelial–mesenchymal transition. Primary mesenchymal tumors and neuroendocrine neoplasms were excluded because immunohistochemistry was negative for anaplastic lymphoma kinase (ALK), smooth muscle actin (SMA), desmin, CD34, signal transducer and activator of transcription 6 (STAT6), S100, HMB45, CD117, discovered on GIST-1 (DOG1), CD56, progesterone, and synaptophysin. However, despite multiple rounds of systemic chemotherapy, immunotherapy, and radiation, his pancreatic disease rapidly deteriorated and metastasized to the liver and bone. Conclusions: Despite multiple lines of treatment, the patient’s condition worsened and he succumbed to his pancreatic malignancy. This study highlights the clinical characteristics, diagnosis, and treatment of rare pancreatic cancer, emphasizing the importance of molecular testing and histopathological biomarkers in personalizing treatment. It also provides insights into promising therapeutic approaches for similar cases with an unusual presentation.

Perineuriomatous Melanocytic Nevi: A Case Series of Four Cases.

Melanocytic tumors with perineuriomatous differentiation may pose diagnostic challenges. This study explores characteristics of perineuriomatous melanocytic nevi, an entity merging features of perineurioma and melanocytic nevi. The aim is to elucidate histopathological features of perineuriomatous nevi to allow dermatopathologists to recognize them and differentiate them from other spindle cell lesions. This study reviews four cases (2020-2023) of melanocytic nevi with perineuriomatous components. All cases comprised adults (median age: 64.50, mean age: 60.25), with a female predominance, and exhibited clinical features characterized by irregular brown macules or papules on the trunk and extremities. Histopathologically, all lesions were compound, and biphasic patterns were evident, encompassing superficial nevoid and deeper spindled populations arranged in whorled fascicles and embedded in a sclerotic or myxoid stroma. Immunohistochemistry revealed expression of at least one perineuriomatous marker in deeper cells. Cases were assessed and compared with previously published cases for comprehensive insights. Three of our four cases demonstrated the presence of a junctional component that was smaller than the dermal component. We suggest that this unusual feature, which we term the "reverse shoulder", may allow dermatopathologists to help consider perineurial differentiation in the appropriate setting. Perineuriomatous nevi can pose diagnostic challenges. This study contributes to the growing body of literature on perineuriomatous nevi, emphasizing their unique features and the importance of accurate diagnosis to avoid unnecessary interventions.

Spindle Cell Variant of Rhabdomyosarcoma: An Aggressive Clinical Case of the Oral Cavity

Rhabdomyosarcoma (RMS) is a malignant, soft tissue neoplasm consisting of cells derived from the primitive mesenchyme that exhibit a profound tendency to myogenesis. Historically, the spindle cell and sclerosing variants were subcategorized under embryonal type RMS. Spindle cell/sclerosing RMS (S-ScRMS) was recently recognized in 2013 by the World Health Organization as a stand-alone entity. Current data support that certain S-ScRMS cases have a more aggressive clinical course with a reduction of long-term survival, and those found in the head and neck region often exhibit extensive local recurrence. Here, we highlight an aggressive clinical course of S-ScRMS by presenting a case of a 7-year-old male child who presented with complaints of swelling in left cheek since 15 to 20 days. It was associated with pain. He was diagnosed as S-ScRMS and received chemotherapy but the disease was aggressive and progressed on chemotherapy. He received radiation but still the disease was inoperable, hence was kept on supportive care.

Unicentric Castleman Disease: Updates and Novel Insights Into Spindle Cell Proliferations and Aggressive Forms of a Localized Disease.

Castleman Disease (CD) is a rare lymphoproliferative disorder that can be separated into two primary forms: Unicentric Castleman disease (UCD) and multicentric Castleman disease (MCD). UCD is localized, while MCD is systemic. Though UCD generally has a favorable prognosis following surgical resection, more aggressive forms of this disease have been identified, including cases associated with dendritic and spindle cell proliferation. Genetic analysis has deepened our understanding of UCD. Despite advancements in better understanding the pathophysiology of UCD, challenges persist in the diagnosis, management, and treatment due to its rarity and heterogeneity. Here, we review current knowledge on UCD, highlighting the epidemiology, clinical presentation, diagnostic criteria, and treatment options while emphasizing the need for further research and innovation in therapeutic strategies.

Intracranial pleomorphic liposarcoma misclassified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier: illustrative case.

Recently, it has been shown that DNA methylation arrays and German Cancer Research Center (Deutsches Krebsforschungszentrum) methylation classifiers are useful aids in brain tumor diagnosis for cases in which histopathological diagnosis is difficult. However, not enough is known about diagnostic aids for intracranial liposarcoma (LPS). An 18-year-old woman with a history of natural killer/T-cell lymphoma, which had been treated with a bone marrow transplant and total body irradiation at age 11 years, presented with diplopia. Magnetic resonance imaging revealed a brain tumor in the posterior left temporal lobe, which was removed by craniotomy. The tumor was initially diagnosed as pleomorphic xanthoastrocytoma through histopathological and DNA methylation examination. She also had a soft tissue tumor in her left thigh, which was removed. It contained spindle cells with oval nuclei and highly pleomorphic cells and was diagnosed as radiation-induced LPS. Histopathological re-examination of the brain tumor led to a final diagnosis of pleomorphic LPS. In this report, the authors describe the case of a patient with an intracranial pleomorphic LPS that was initially classified as a pleomorphic xanthoastrocytoma by a DNA methylation classifier. Although DNA methylation classifiers are useful as diagnostic aids in cases in which definitive pathology is difficult to determine, there is a risk of misdiagnosis in some types of tumors. https://thejns.org/doi/10.3171/CASE24465.

Perianal leiomyosarcoma as a rare sequela of rectal cancer radiotherapy: a case report

Radiation-induced sarcomas (RIS) are iatrogenic malignancies that arise following high-dose radiotherapy, posing a significant clinical challenge due to their poor prognosis and resistance to conventional treatments. The incidence of RIS is increasing with advancements in radiotherapy techniques. This report presents a case of a 71-year-old male diagnosed with stage III rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy and curative surgery. Three years postoperatively, he developed a low-grade radiation-induced leiomyosarcoma in the perianal region. Histopathological examination confirmed a spindle cell neoplasm with notable immunohistochemical markers. RIS often presents as aggressive high-grade tumors resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment. This case underscores the importance of long-term surveillance post-radiotherapy and highlights the need for innovative therapeutic strategies, including immunotherapy. Despite being rare, RIS poses a significant risk following cancer treatment, making early detection through vigilant monitoring and advancements in therapeutic approaches crucial for improving patient outcomes.

Desmoplastic Fibroblastoma (Collagenous Fibroma) of the Knee: A Case Report and Literature Review.

Desmoplastic fibroblastoma, also known as collagenous fibroma, is a rare benign mesenchymal neoplasm that primarily arises in the subcutaneous tissue of upper extremities and limb girdles. The knee is an uncommon location for desmoplastic fibroblastoma. Recent studies have demonstrated the presence of immunoreactivity for FOS like 1 (FOSL1) and rearrangements of FOSL1. A 70-year-old woman presented with a 1-year history of a palpable mass in the medial aspect of the right knee. Physical examination revealed a 4-cm, elastic hard, mobile, nontender mass. Magnetic resonance imaging (MRI) showed a well-defined mass with prominent low signal intensity on all pulse sequences. Contrast-enhanced MRI demonstrated mild internal enhancement with rim enhancement. After an open biopsy, the lesion was successfully treated by complete excision. Histologically, the tumor was composed of bland spindle or stellate-shaped cells embedded in an abundant collagenous stroma. Immunohistochemically, the tumor cells showed diffuse nuclear positivity for FOSL1. These findings were consistent with a diagnosis of desmoplastic fibroblastoma. The patient was asymptomatic and there was no evidence of local recurrence eight months after surgery. Desmoplastic fibroblastoma is a distinctive benign soft-tissue tumor with FOSL1 immunoreactivity and should be clearly distinguished from more biologically aggressive mesenchymal neoplasms.

PROGNOSTIC IMPLICATIONS ACROSS HISTOLOGICAL SUBTYPES OF HEAD AND NECK SQUAMOUS CELL CARCINOMA: AN UPDATE.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide, arising from the mucosal epithelium of the oral cavity, oropharynx, hypopharynx, nasopharynx, larynx, and sinuses. In addition to the conventional morphologic pattern characterized by the degree of cellular atypia and squamous differentiation, HNSCC is classified into eight histopathologic subtypes: basaloid, spindle cell, adenosquamous, carcinoma cuniculatum, verrucous, lymphoepithelial, papillary, and acantholytic. This review provides a comprehensive review of the literature on the prognostic implications of the histological subtypes of HNSCC. Although there is extensive literature on HNSCC, few studies specifically focus on the treatment and prognosis of its histopathologic subtypes. Among these subtypes, verrucous squamous cell carcinoma and carcinoma cuniculatum generally have a favorable prognosis, while others, such as basaloid and spindle cell squamous cell carcinoma, tend to follow a more aggressive clinical course. In this review, we delve into the histopathological subtypes of HNSCC and explore their clinicopathological, molecular, and prognostic findings. Further molecular investigations aimed at identifying targeted therapies for these subtypes are necessary. Moreover, it is crucial to recognize the emerging histopathological variants documented in the literature, considering the ongoing limitations in prognostic assessment.

Genomic landscape of superficial malignant peripheral nerve sheath tumor

Superficial malignant peripheral nerve sheath tumors (SF-MPNSTs) are rare cancers and can be difficult to distinguish from spindle cell (SCM) or desmoplastic (DM) melanomas. Their biology is poorly understood. We performed whole-exome sequencing (WES) and RNA sequencing (RNA-seq) on SF-MPNST (n=8) and compared these to cases of SCM (n=7), DM (n=8), and deep MPNST (D-MPNST, n=8). Immunohistochemical staining for H3K27me3 and PRAME was also performed. SF-MPNST demonstrated intermediate features between D-MPNST and melanoma. Patients were younger than those with melanoma, and older than those with D-MPNST; outcome was worse and better respectively. SF-MPNST tumor mutational burden (TMB) was higher than D-MPNST and lower than melanoma; differences were significant only between SF-MPNST and SCM (p = 0.0454) and between D-MPNST and SCM (p = 0.001, Dunn's Kruskal-Wallis post-hoc test). Despite having an overlapping mutational profile in some common cancer-associated genes, the COSMIC mutational signatures clustered DM and SCM together with ultraviolet light exposure signatures (SBS7a, 7b), and SF- and D-MPNST together with defective DNA base excision repair (SBS30, 36). RNA-seq revealed differentially expressed genes between SF-MPNST and SCM (1670 genes), DM (831 genes), and D-MPNST (614 genes), some of which hold promise for development as immunohistochemical markers (SOX8, PLCH1) or aids (MLPH, CALB2, SOX11, TBX4). H3K27me3 immunoreactivity was diffusely lost in most D-MPNSTs (7/8, 88%), but showed variable and patchy loss in SF-MPNSTs (2/8, 25%). PRAME was entirely negative in the majority (0+ in 20/31, 65%), including 11/15 melanomas, and showed no significant difference between groups (p=0.105, Kruskal-Wallis test). Expression of immune cell transcripts was upregulated in melanomas relative to MPNSTs. Next-generation sequencing revealed multiple differential features between SF- MPNST, D-MPNST, SCM, and DM, including tumor mutation burden, mutational signatures, and differentially expressed genes. These findings help advance our understanding of disease pathogenesis and improve diagnostic modalities.

Superficial ALK-rearranged myxoid spindle cell neoplasms: Clinicopathologic and molecular analysis of two cases and a review of the literature

Superficial anaplastic lymphoma kinase (ALK)-rearranged myxoid spindle cell neoplasms are a recently identified subtype of cutaneous soft tissue tumors, distinct for their co-expression of CD34 and S100 and characterized by ALK gene rearrangements. Although 72 cases have been reported primarily as isolated case reports, this tumor subtype has yet to be included in the WHO classification of soft tissue tumors, underscoring the need for further study. In this study, we diagnosed two additional cases, both arising in the dermis and subcutaneous tissue. These tumors exhibited characteristic pathological features, including linear or concentric whorl patterns, prominent myxoid and collagenized stroma, mild cellular atypia, and rare mitotic activity. The presence of infiltrative margins and the potential for recurrence after surgery suggest at least locally aggressive clinical behavior. Immunohistochemically, the tumors diffusely expressed S100 and CD34, with strong ALK-D5F3 positivity, confirmed by ALK gene rearrangement. These findings further expand the clinical and pathological spectrum of ALK-rearranged neoplasms and highlight the need for continued research on their biological behavior and classification.

Perinephric Myxoid Pseudotumor of Fat: A Series of 13 Cases and Literature Review

Perinephric myxoid pseudotumor of fat (PMPF) is a recently described and rare retroperitoneal mass-forming lesion whose clinical significance chiefly involves mimicry of a variety of soft tissue tumors. For unknown reasons, it commonly occurs in male patients with underlying non-neoplastic renal diseases and/or type 2 diabetes (DMT2). A total of 55 cases have been reported in the literature. Recently, we have encountered 13 such masses with peculiar histologic features; thus, we sought to investigate our experience and review the clinicopathologic characteristics of the literature. Our series confirms that PMPF frequently occurs in adult male patients (11/13, 85%), with an average age of 66 years, and commonly co-occurs with renal disease, such as DMT2 (2/13, 15%), end-stage renal disease (ESRD) (5/13, 39%), renal cysts (4/13, 31%), concurrent or prior renal neoplasia (2/13; 15%), and myeloma/lymphoma (2/13; 15%). Histologic evaluation shows lipomatous masses commonly showing variable amounts of fat necrosis, myxoid degeneration, lymphoplasmacytic inflammation and lacking atypical hyperchromatic stromal spindle cells. Unusual histologic features include extramedullary hematopoiesis (1/13, 8%), hemosiderin deposition (4/13, 31%), and small wisps of mature smooth muscle (6/13, 46%). All cases tested were negative for MDM2 and did not show an increased ratio of IgG4+/IgG+ plasma cells. Our study confirms the clinical and pathologic features of PMPF and expands its histologic spectrum, underscoring the importance of this entity as a benign pseudotumor which should be included in the differential diagnosis of other fat-containing retroperitoneal masses, particularly well-differentiated liposarcoma.

Malignant Peripheral Nerve Sheath Tumor (MPNST) With Smooth Muscle Differentiation of the Uterus-A Case Report With Emphasis on Diagnostic Pitfalls and Value of DNA Methylation Analysis.

With no more than two dozen cases reported in the literature, malignant peripheral nerve sheath tumor (MPNST) is a rare primary mesenchymal neoplasm arising in the female genital tract. Most cases occurred in middle-aged adults with high grade histology, unfavorable clinical outcome, and no history of neurofibromatosis type 1. Its extreme rarity in this site no doubt poses a diagnostic challenge during routine clinical practice. In the following, we report an additional case of uterine MPNST occurring in a 49-year-old Chinese woman, which was initially misdiagnosed as a leiomyosarcoma. The primary tumor showed two distinctive components-a high-grade poorly differentiated component with markedly pleomorphic spindle cells arranged in a peritheliomatous pattern; and a leiomyosarcoma-like (LMS-like) component with tumor cells displaying obvious myoid differentiation. The patient suffered a recurrence less than 2 years later with the recurrent tumor demonstrating similar features to the high-grade component of the primary tumor. The patient eventually succumbed 46 months later after developing another recurrence despite receiving targeted therapy and chemotherapy. On retrospective molecular analysis, no clinically relevant fusion transcript was detected on RNA sequencing. Interestingly instead, DNA methylation analysis showed the tumor clustered with the "MPNST" group in the German Cancer Research Center (DKFZ) sarcoma classifier. The tumor was also found to have EED gene homozygous deletion, multiple copy number alterations and loss of H3K27me3 expression in both high-grade and LMS-like components. Combining histology with all the ancillary tests results, the diagnosis was most consistent with MPNST. Our case highlights the diagnostic pitfalls for MPNST arising in the female genital tract and the potential clinical utility of DNA methylation analysis.

Pediatric Mesenchymal Tumor With MN1::TAF3 Fusion.

MN1 fusion is emerging as oncogenic in soft-tissue tumors. Here, we provided detailed clinicopathological documentation of a tumor with MN1::TAF3 fusion. The tumor developed on the face of an 8-year-old boy and did not recur or metastasize for 5 years after surgery without adjuvant therapy. Histologically, the tumor predominantly comprised sheets and nests of atypical, mildly pleomorphic epithelioid cells. Mallory body-like eosinophilic cytoplasmic inclusions, small round cells, and fascicles of spindle cells were focally observed. Mitotic activity was high, and focal necrosis was present. Immunohistochemically, the tumor was positive for cytokeratin AE1/AE3 in the epithelioid cell component but otherwise showed nonspecific phenotypes. Targeted RNA sequencing identified an in-frame MN1 (exon 1)::TAF3 (exon 3) fusion transcript. We validated the transcript with reverse transcription-polymerase chain reaction, Sanger sequencing, and MN1 break-apart fluorescence insitu hybridization. MN1::TAF3 was previously listed without details in a large-scale sequencing study involving a pediatric round cell sarcoma in the orbit, raising the possibility that these tumors might form a coherent group.

Reevaluating hybrid neurofibroma/schwannoma: Predominance of schwannoma features despite CD34 positivity and initial neurofibroma diagnosis.

Schwannomas consist of both high-cellularity regions (Antoni A area) and hypocellular regions (Antoni B area) in histopathological findings. Neurofibromas characteristically consist of CD34 positive spindle cells with thin, wavy, nuclei and wavy collagen bands. Previous reports have described segments of schwannomas with neurofibroma features as hybrid tumors, although hybrid tumors were diagnosed based on partial CD34 positivity in many previous reports. On the other hand, the Antoni B area of some schwannomas was reported to be positive for CD34. Therefore, the definition of a hybrid tumor has not been clear. The objective of this study was to determine whether only CD34 positive findings in schwannomas could be used to define a hybrid tumor. In the analysis of our patient with schwannomatosis caused by a novel LZTR1 germline mutation, part of the tumor had CD34 positive hypocellular regions. These regions contained no thin, wavy, nuclei, indicating an Antoni B area. Laser microdissection was used to investigate the genetic background and differences in molecular mechanisms between CD34 positive and CD34 negative regions. All mutations identified in CD34 positive regions were also found in CD34 negative regions. Our data could not clear the genetic background of Antoni B which was CD34 positive area. We then reviewed the pathologies of 66 sporadic schwannomas. Histopathological examinations of all schwannomas revealed the absence of thin, wavy, nuclei and wavy collagen bands, and no hybrid tumors were found in any of the cases. Ten of 66 patients were randomly selected for CD34 immunostaining and positivity was found in all cases. Our data suggest that it is difficult to distinguish schwannomas by staining for CD34 alone, as Antoni B areas can also be positive for CD34. Therefore, CD34 staining alone should not be used to diagnose hybrid tumors in patients with schwannomas.