Spindle Cell Tumor Research Articles

Wolves in Sheep's Clothing and Vice Versa: Fine-Needle Aspiration of Low-Grade Spindle Cell Lesions

Abstract The morphologic overlap between low-grade spindle cell lesions can lead to diagnostic dilemmas, particularly when attempting to interpret limited material. Evaluation of such specimens frequently requires correlating with clinical and imaging findings, as well as ancillary studies. We discuss the case of a 78-year-old woman with a remote history of breast carcinoma who presented with a left base of neck nodule. While imaging findings were highly suggestive of schwannoma, fine-needle aspiration biopsy of the nodule was performed for diagnostic confirmation. The patient reported tingling and an electrical shock sensation traveling down her arm during the fine-needle aspiration procedure. Cytomorphologic findings demonstrating a low-grade spindle cell neoplasm further supported a diagnosis of schwannoma, despite early immunohistochemistry results not being supportive. A last-minute suggestion that the differential diagnosis be broadened prompted additional immunohistochemical workup and follow-up molecular testing that confirmed an alternative diagnosis of solitary fibrous tumor. This case demonstrates the importance of correlating clinical, radiologic, and pathologic findings when approaching the differential diagnosis of low-grade spindle cell lesions on fine-needle biopsy specimens. Ancillary testing including immunohistochemistry, molecular studies, or fluorescence in situ hybridization is frequently utilized to establish a definitive diagnosis.

NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities.

Undifferentiated round cell sarcomas (URCS) of soft tissue and bone and tumours of uncertain differentiation (TUD) are commonly ascribed to a subset of neoplasms with low frequency of NTRK gene fusions. However, more recently NTRK-rearranged round and spindle cell tumours have been noted in case reports and in limited or heterogeneous cohorts. The aim of our study was to investigate the presence of NTRK gene fusions in a large retrospective cohort of paediatric URCS and TUD after a systematic review of the diagnosis, according to the recently updated WHO classification scheme. One-hundred and five patients with diagnosis of URCS or TUD, involving the bone or soft tissue, were retrospectively evaluated. After the case selection and the histopathological review of the case cohort, pan-Trk immunohistochemistry (IHC) testing was performed on formalin-fixed paraffin-embedded (FFPE) tissues. Tumour RNA was extracted from FFPE tissue and subjected to next-generation sequencing (NGS) library preparation, using a 10-gene NGS fusion panel, sequenced on an Illumina MiSeq. The NGS-positive cases were further confirmed by real-time PCR. On immunohistochemical screening, 12/105 (11.4%) cases were positive using the pan-Trk antibody, showing three different staining patterns with the cytoplasmic distribution being most common. Molecular analysis using NGS and confirmed by the real-rime PCR detected two positive cases for the ETV6-NTRK3 fusion. The histological pattern of the two positive cases, together with the demonstration of the NTRK rearrangement, leaded to re-classify these previously not otherwise specified sarcomas with uncertain differentiation into the emerging category of NTRK-rearranged neoplasms. In addition, we found the two NTRK fused neoplasms showing a clinical indolent course, in contrast with literature.

Malignant peripheral nerve sheath tumor of temporoparietal region of brain mimicking as glioma: A rare case report

Malignant peripheral nerve sheath tumor (MPNST) is exceedingly rare to occur intracerebrally. The incidence of this subtype is 0.001%. Their typical origin is from peripheral nerves of the limbs, trunk, and lumbar and brachial plexuses. It carries a poor prognosis despite aggressive management due to high chances of local recurrence. We present a case of MPNST occurring intracerebrally in a 60-year-old male patient. Imaging showed a 63 × 74 × 46 mm mass lesion in the left temporoparietal region with mass effect. The patient underwent left temporoparietal craniotomy with maximum gross dissection of the tumor. Histopathology was suggestive of spindle cell neoplasm. On immunohistochemistry, cells were positive for S-100 and SOX-10, which are consistent with the diagnosis of MPNST. The post-operative contrast-enhanced magnetic resonance imaging brain showed gross residual disease. Post-operative radiotherapy was given of intensity-modulated radiation therapy and chemotherapy of doxorubicin and ifosfamide.

Mammary‐type myofibroblastoma of the perineum: Typical or rare location?

IntroductionMammary‐type myofibroblastoma is a rare benign tumor, mainly arising along the embryonal mammary ridge. We report a rare case of mammary‐type myofibroblastoma of the perineum.Case presentationA 37‐year‐old Japanese man presented with a 20 mm, progressively‐growing painless mass in the right perineum. Computed tomography showed a subcutaneous tumor with a strong contrast effect. Upon total resection, pathology showed a spindle‐cell tumor positive for desmin but negative for CD34. Further immunohistochemistry showed loss of Rb expression, leading to differential diagnosis. We could not evaluate the exact rarity of the perineal location due to categorization in past reports.ConclusionDue to the similarities between mammary and anogenital tissue, we suggest that tallying perineal and vulvar areas separately from the embryonic mammary ridge sites may be beneficial in gaining insight into the pathophysiology of this tumor.

Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib.

We describe two poorly differentiated, non-myofibroblastic (SMA-, S100+, CD34±), spindle cell neoplasms with immunohistochemical positivity for ALK and with ALK gene rearrangements leading to PLEKHH2::ALK and CLTC::ALK fusions, respectively. ALK protein overexpression and/or gene fusions should be evaluated in poorly differentiated spindle cell neoplasms, even when there is an absence of a myofibroblastic phenotype. A positive ALK evaluation has therapeutic implications as both tumors responded to single-agent treatment with the tyrosine kinase inhibitor crizotinib.

Glioblastoma, IDH-Wild Type With FGFR3-TACC3 Fusion: When Morphology May Reliably Predict the Molecular Profile of a Tumor. A Case Report and Literature Review.

It has been reported that in-frame FGFR3-TACC3 fusions confer to glioblastomas, IDH-wild type (GBMs, IDHwt) some unusual morphologic features, including monomorphous rounded cells with ovoid nuclei, nuclear palisading, endocrinoid network of “chicken-wire” vessels, microcalcifications and desmoplastic stroma, whose observation may predict the molecular profile of the tumor. We herein present a case of recurrent GBMs, IDHwt, exhibiting some of the above-mentioned morphological features and a molecularly-proven FGFR3-TACC3 fusion. A 56-year-old man presented to our hospital for a recurrent GBM, IDHwt, surgically treated at another center. Histologically, the tumor, in addition to the conventional GBM morphology, exhibited the following peculiar morphologic features: (1) monomorphous neoplastic cells with rounded nuclei and scant pale cytoplasm; (2) thin capillary-like vessels with “chicken-wire” pattern; (3) nuclear palisading; (4) formation of vague perivascular pseudorosettes; (5) spindled tumor cells embedded in a loose, myxoid background. Based on this unusual morphology, molecular analyses were performed and an FGFR3 exon17-TACC3 exon 10 fusion was found. The present case contributes to widening the morphologic spectrum of FGFR3-TACC3-fused GBM, IDHwt and emphasizes that pathologists, in the presence of a GBM, IDHwt with unconventional morphology, should promptly search for this fusion gene.

Case Report: Giant Multiloculated Pseudocystic Jejunal Leiomyosarcoma in a Dog: Atypical Morphologic Features of Canine Intestinal Leiomyosarcoma

A 10-year-old intact female Rottweiler dog weighing 29 kg presented with 2 days history of vomiting, anorexia, and lethargy to KonKuk University Teaching Hospital, Seoul, South Korea. Ultrasonography and computed tomography (CT) scannings revealed a well-demarcated, large mass (29 × 19 × 11 cm) with numerous fluid-filled cavities. Metastases to adjacent lymph nodes were also identified on CT. This large mass and the affected intestinal segments were excised for palliative purposes. Postoperatively, the dog recovered uneventfully without any complications. The cut surface of the mass showed an exophytic growth pattern of multiloculated cystic lesions filled with serosanguineous fluid, large cavities filled with necrotic exudate, and fistulous connections between the intestinal lumen and the necrotic cavity in the mass. On histopathology, the mass was a spindle cell neoplasm expanding from the jejunal muscular layer and with pseudocystic changes. Additional immunohistochemical analysis using antibodies against smooth muscle actin, desmin, and CD-117 demonstrated that the mass was consistent with a leiomyosarcoma. Six months post-operatively, plain radiography revealed an abdominal mass, suspected to be recurrence from jejunal leiomyosarcoma. The owner decided to euthanize the dog due to financial constraints. This case report describes the atypical morphology and clinical progression of a large canine jejunal leiomyosarcoma, which had similar clinical features as those of human leiomyoma and leiomyosarcoma.

Expanding the molecular spectrum of congenital mesoblastic nephroma: A rarely described KIAA1549::BRAF fusion in a classic variant

Congenital mesoblastic nephroma (CMN) are low grade spindle cell neoplasms with myofibroblastic differentiation and are classified morphologically as classic, cellular, or mixed. Recurrent genetic alterations have been identified – EGFR internal tandem duplication is associated with classic morphology, and ETV6::NTRK3 fusion is associated with the cellular subtype. We report a case of a classic variant of CMN with a rarely described KIAA1549::BRAF fusion.

Malignant gastrointestinal neuroectodermal tumor in head and neck: two challenging cases with diverse morphology and different considerations for differential diagnosis.

Malignant gastrointestinal neuroectodermal tumor (MGNET) is a sarcoma typically involving the gastrointestinal tract with neuroectodermal differentiation and EWSR1-ATF1/CREB1 fusions. Recently, rare MGNET cases were reported in extragastrointestinal sites. We identified 2 cases of MGNET arising in unprecedented laryngeal and intracranial locations, respectively. Both cases showed spindle and epithelioid tumor cells with amphophilic to clear cytoplasm and occasionally prominent nucleoli, arranged in solid, fascicular, and pseudoalveolar patterns. Case 1 exhibited moderate to marked nuclear atypia and focal intraepithelial component. In contrast, case 2 comprised predominantly low-grade epithelioid cells with extensive pseudopapillary structures. Both tumors showed an S100/SOX10-positive and HMB45/melan-A-negative immunoprofile as well as EWSR1-ATF1 fusion. A chief obstacle in diagnosing case 1 was the histologic and immunophenotypic resemblance to melanoma. The striking pseudopapillary architecture and the intracranial location of case 2 rendered differential diagnoses including meningioma and ependymoma. With the peculiar locations and morphology, these cases posed great diagnostic challenge.

NTRK-rearranged spindle cell neoplasm of the lower extremity: radiologic-pathologic correlation.

Neurotrophic tyrosine receptor kinase (NTRK)-rearranged spindle cell neoplasm is a recently characterized soft tissue tumor and has been classified as provisional by the World Health Organization. Detection of the genetic rearrangement is important because these tumors are amenable to targeted tyrosine kinase inhibitor therapy, which can play a key role in patients with unresectable or advanced disease. Although the spectrum of histopathology associated with this entity is broad, one notable feature is the infiltrative growth pattern, which is most reminiscent of lipofibromatosis-like neural tumor. Description of their diverse histologic attributes has aided recognition, but so far little attention has been paid to correlating the gross appearance and imaging features of these lesions. In this report, we describe the clinical, imaging, histopathological, and genetic features of a soft tissue NTRK-rearranged spindle cell neoplasm. Inclusion of this more recently identified entity into the imaging differential of tumors with intratumoral relatively hypovascular nodules and infiltrative margins is important because testing for NTRK rearrangement is not routinely performed.

Spindle cell tumors of the pleura and the peritoneum: pathologic diagnosis and updates.

A diverse group of both benign and malignant spindle cell tumors can involve the pleura or the peritoneum. Due to their rarity and overlapping morphologic features, these tumors can pose considerable diagnostic difficulty in surgical pathology. As these tumors differ in their prognosis and clinical management, their correct pathologic diagnosis is critical. In addition to histologic assessment, select immunohistochemical and molecular tools can aid the distinction among these tumors. In this review, we consider some of the major histologic differential diagnosis of spindle cell tumors involving these serosal membranes. This list of tumors includes solitary fibrous tumor, inflammatory myofibroblastic tumor, desmoid fibromatosis, synovial sarcoma, sarcomatoid carcinoma, spindle cell melanoma, dedifferentiated liposarcoma, epithelioid hemangioendothelioma, and sarcomatoid mesothelioma. We describe their salient clinicopathologic and genetic findings, with a review on some of the recent discoveries on their molecular pathogenesis.

The ultrasonographic characteristics of female periurethral solid masses.

Studies on the imaging of female periurethral masses are sparse, and most are focused on cystic lesions. In this article, we studied female periurethral solid masses and reported their ultrasonographic features. Fifteen women with periurethral solid masses pathologically diagnosed between January 2008 and April 2021 were assessed. Each patient had only one mass. The pathological types included urethral caruncle (5 patients), urethral leiomyoma (3 patients), urethral malignant tumor (MT) (3 patients), periurethral spindle tumor (3 patients) and cartilage necrosis of pubic symphysis (PS) (1 patient). On ultrasound, all urethral caruncles were located at the urethral meatus. They were hypoechoic/isoechoic and rich in blood flow signal. Each leiomyoma presented as a well-defined hypoechoic mass with an oval shape. The urethral MT had inhomogeneous/isoechoic echoes, with medium to abundant blood flow signal. The spindle cell tumors had regular/irregular shapes, moderate/high density echogenicity and little/rich blood flow signals. The articular cartilage necrosis of PS was regular in shape, with mixed echogenicity and no blood flow. Ultrasound imaging is a convenient and useful method to evaluate the morphological characteristics of female periurethral solid masses.

ALK rearrangements in infantile fibrosarcoma-like spindle cell tumours of soft tissue and kidney.

Recurrent alterations in receptor tyrosine kinase (RTK) and downstream effectors are described in infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) and a subset of spindle cell sarcomas, provisionally designated 'NTRK-rearranged' spindle cell neoplasms. These two groups of tumours demonstrate overlapping morphologies and harbour alterations in NTRK1/2/3, RET, MET, ABL1, ROS1, RAF1 and BRAF, although their relationship is not fully elucidated. We describe herein a cohort of paediatric tumours with clinicopathological features not typical for inflammatory myofibroblastic tumour, but rather with similarities to cCMN/IFS harbouring ALK fusions. Clinicopathological features were assessed and partner agnostic targeted RNA sequencing on clinically validated platforms were performed. Tumours occurred in patients aged from 2 to 10 years (median age 2 years) with a 2:2 male to female ratio and an average size of 8.4 cm. Two tumours arose in soft tissues and two in the kidney. Morphological features included spindle to ovoid cells arranged in long fascicles or haphazardly within a myxoid to collagenised stroma; a subset of cases had either dilated, ectatic vessels or focal perivascular hyalinosis. By immunohistochemistry, all cases tested showed cytoplasmic expression of anaplastic lymphoma kinase (ALK) and one case demonstrated co-expression of CD34 and S100. This series of ALK-rearranged IFS-like tumours expands the spectrum of targetable kinases altered in these tumours and reinforces the potential overlap between IFS/cCMN-like tumours and the provisional entity of 'NTRK-rearranged' spindle cell neoplasms.

Rare and Aggressive Primary Amelanotic Melanoma in Anorectal Region: A Case Series

Anorectal amelanotic melanoma is a rare and aggressive disease with high morbidity and mortality. A conclusive diagnosis of anorectal amelanotic melanoma poses a challenge to pathologists and clinicians due to the protean nature of this entity, be it in its initial clinical assessment appearing as non pigmented polypoidal growths usually mistaken for haemorrhoids or anorectal polyps. Histomorphologically, these entities get categorised in bewildering array of diagnoses like spindle cell carcinoma, Gastrointestinal Stromal Tumour (GIST), High grade sarcomas and even lymphoma. Thus Immunohistochemistry (IHC) remains a vital tool for conclusive diagnosis. The purpose of the present case series is to discuss in detail about the three patients all aged above 55 years and clinically assessed with anorectal polypoidal growths. All three cases on histopathological evaluation were diagnosed as spindle cell neoplasm with no discernible melanin pigments. The IHC performed on all three cases turned positive for S-100 and Human Melanoma Black 45 (HMB 45). This case series highlights the challenging and bewildering nature of presentation of anorectal amelanotic melanomas, by virtue of its rarity and hence justifies the need for it to be considered as a possible differential diagnosis.

BCOR overexpression in pediatric sarcomas: A morphologic continuum of mixed round and spindle cell tumors

BCOR overexpression in pediatric sarcomas: A morphologic continuum of mixed round and spindle cell tumors

A Nine Years Histopathological Retrospective Study of Retroperitoneal Masses

Introduction: Retroperitoneum is potentially large space that allows both primary and metastatic tumours to grow silently before clinical signs and symptoms appear. However, retroperitoneal masses due to their unhinhibited growth and with no facial boundaries they are often attain large size before the development of symptoms and the establishment of a diagnosis. There are a vast number of neoplasms occurring in this region. Understanding the pathology and lesions is important, for early diagnosis and for treatment of these neoplasms. Aim: To study the overall prevalence of primary and secondary retroperitoneal neoplasms and the varied histomorphological spectrum of retroperitoneal masses. Also to categorise the lesions as benign and malignant tumors of retroperitoneum. Materials and Methods: This retrospective study was conducted in the Department of Pathology, Karnataka Institute of Medical Sciences Hubballi, Karnataka, India from 2011 to 2019. A total of 39,757 speimens were recieved to histopathology section during this period. Among them, 53 (0.13%) were retroperitoneal tumours. Haematoxylin and Eosin stained slides were thoroughly analysed and categorised into non neoplastic, benign and malignant tumours. Further, based on the finer microscopic features, the accurate subtype of the tumour type was made. The descriptive statistics like mean, range and percentage are used. Results: Total 53 cases of retroperitoneal tumours were studied of which 10 (18.9%) cases were primary retroperitoneal masses and 43 (81.1%) cases were secondary retroperitoneal masses. Mean age was 40.7 years with male to female ratio 1.5:1. Malignant lesions were more common accounting to 50.9% cases, followed by benign 22.64% cases, the rest were intermediate grade and inflammatory. Kidney lesions were most common secondary retroperitoneal masses, accounting for 41.5% cases, followed by pancreas 22.64% cases, adrenals 13.20% cases and Lymphnodes 3.7% cases. Primary retroperitoneal masses which accounted for 18.9% cases were, categorised histomorphologically as spindle cell tumours, adipocytic, small round cell tumours, cartilaginous origin and cystic lesions. Conclusion: Diagnosis of retroperitoneal tumours is challenging due to their varied histomorphology and histopathology forms the gold standard for diagnosis.

Malignant extragastrointestinal stromal tumor: A challenging diagnosis due to unusual presentation

Gastrointestinal stromal tumors are the most common mesenchymal tumors of gastrointestinal tract which comprise <1% of all primary gastrointestinal malignancies. These tumors show mutations in the KIT gene or platelet-derived growth factor receptor-A gene and usually stains positively for CD117. Very few cases of extragastrointestinal GIST (EGIST) have been reported in literature which originate from omentum and mesentery as per our knowledge. Here, we report a case of EGIST arising from omentum with no connection to gastrointestinal tract organs in a 60-year-old woman who presented with abdominal pain for 2–3 months. Intraoperative findings showed the presence of multiple globular masses and nodules in the peritoneal cavity. Microscopically, the spindled tumor cells were arranged in interlacing fashion. Immunohistochemistry showed positivity for CD117 and negativity for smooth muscle actin (SMA). Thus, EGIST should always be considered as a differential diagnosis for nodular mesenteric masses.

Case series: Benefit of Angioembolization prior to surgery for Giant fibrous pleural tumors

Only 5% of malignant pleural neoplasms are fibrous tumors of the pleura that typically develop from sub-mesothelial mesenchymal tissue of the visceral pleura. When a tumor measures more than 15 cm, it is referred to as a "giant." The best option for treating both benign and malignant neoplasms is surgery. We conducted a retrospective analysis of the three case series of pleural large fibrous tumors. Additionally, we will discuss our experience with pre-surgical Angioembolization, involving implanting coils and plugs, to treat spindle cell neoplasm. Surgery was completed without any issues.

Solitary Fibrous Tumour of Liver Presenting as Doege–Potter Syndrome – A Case Report

Background: Doege–Potter syndrome is a rare syndrome which is defined as Solitary fibrous tumour (SFT) that is associated with NICTH (non-islet cell tumour hypoglycaemia). Limited case reports are available on Solitary fibrous tumour of liver presenting as Doege–Potter syndrome in published medical literature. Case report: A 60-year-old female presented with episodic weakness and incoherent behaviour since 3 months and during that episode her serum glucose were low which corrected on glucose administration and abdominal distension for 1 month. Abdominal lump was noted in right hypochondrium arising from liver. On investigation- fasting serum glucose levels, fasting insulin levels and fasting C peptide levels were low and serum IGFII levels were elevated. CT abdomen revealed heterogeneously enhancing solitary lesion of 23 x 18 x 14 cm arising from segment 5 ,6, 7, 8 of liver. AFP, CA19-9 levels were within normal range. Liver biopsy shows spindle cell tumour of fibroblastic origin. Anatomical right hepatectomy with MHV preservation was done. Postoperative course was uneventful with symptomatic improvement, serum glucose levels normalised, and patient was discharged on 8th POD. Discussion: Solitary fibrous tumours are uncommon benign or malignant mesenchymal cell tumours which originate from visceral pleura, pelvis, retroperitoneum and liver. Doege–Potter syndrome which is a rare paraneoplastic manifestation of Solitary fibrous tumour, when there is secretion of prohormone - insulin-like growth factor II (IGF-II), causing hypo insulinemic hypoglycaemia and suppressed serum insulin, C peptide and elevated IGFII/IGFI ratio . Definitive treatment is complete tumour resection.

Renal spindle cell tumor with thrombus extension into the inferior vena cava and the right atrium depicted by positron emission tomography/computerized tomography scan

Tumor thrombus (also called intravascular tumor extension) can be defined as tumor extending into the vessel, typically a vein; it occurs in a lot of malignancies such as hepatocellular carcinoma and Wilms tumor. Tumor thrombus has been reported to demonstrate increase in fluorodeoxyglucose (FDG) uptake that would differentiate it from the benign bland thrombus, which would not take up FDG on positron emission tomography/computerized tomography (PET/CT) scan. We present a case of spindle cell sarcoma of the right kidney whose baseline contrast-enhanced CT revealed a mass replacing the right kidney and right renal vein and associated with thrombus in the inferior vena cava (IVC). Fluorine-18 FDG PET/CT imaging was done and revealed an FDG-avid hypermetabolic malignant right renal mass with hypermetabolic IVC thrombus extending to the right atrium.