Adjuvant therapy fails to show survival benefit for patients with spindle cell carcinoma: Evidence from the surveillance, epidemiology, and end results database.

BACKGROUND: Spindle cell carcinoma (SpCC) is a rare tumor type with poor prognosis, and standard treatment modalities are not available yet. However, large-scale studies on this topic are sparse. In this study, data from the surveillance, epidemiology, and end results (SEER) database were used to determine cancer-specific survival (CSS) rates of SpCC and to investigate the impact of different therapeutic strategies including surgery with or without chemotherapy, radiotherapy, or chemoradiotherapy on patient outcome. METHODS: A total of 665 cases of SpCC, diagnosed from 1996 to 2015, were extracted from the SEER database. Kaplan-Meier survival curves and log-rank tests were used to assess CSS rates and differences on survival curves. Multiple COX-proportional hazards models were used to analyze the association between various treatments and prognosis of SpCC patients classified by organs or systems. RESULTS: Different treatments for SpCC in different organ or system were associated with prognosis of SpCC patients. Surgery alone exhibits survival benefit, whereas adjuvant therapy fails to show survival benefit for patients with SpCC. CONCLUSIONS: The prognosis of SpCC patients varied significantly with different clinical treatments. Adjuvant radiotherapy or chemotherapy did not show survival benefit, even increasing the risk of mortality for SpCC patients.

Spitz nevus with a novel TFG-NTRK2 fusion: The first case report of NTRK2-rearranged Spitz/Reed nevus.

Fusions of ALK, ROS1, NTRK1, NTRK3, RET, MET, MERTK, FGFR1, ERBB4, LCK, BRAF, MAP3K8, MAP3K3, and PRKDC and mutation of HRAS have so far been discovered as the genetic alterations associated with the pathogenesis of Spitz neoplasms. This report presents the first case of NTRK2-rearranged Spitz/Reed nevus. The patient was a 39-year-old male with a pigmented macule rapidly growing on his shoulder. Histopathologically, the lesion was a junctional melanocytic nevus composed of large nests of spindled melanocytes with abundant eosinophilic cytoplasm associated with a hyperplastic epidermis. These findings fulfilled the diagnostic criteria of a pigmented spindle cell nevus of Reed (variant of Spitz nevus). Immunohistochemistry for pan-Trk revealed diffuse cytoplasmic positivity in the tumor cells, but immunoexpression of ALK, ROS1, and BRAF V600E was not seen. A novel, in-frame, TFG-NTRK2 fusion was identified by RNA sequencing. This case report expands the list of genetic alterations in Spitz neoplasms and the spectrum of NTRK2-rearranged tumors.

First-line axitinib therapy is less effective in metastatic renal cell carcinoma with spindle histology.

Axitinib, a vascular endothelial growth factor receptor-tyrosine kinase inhibitor, will be used in combination first-line therapies against metastatic renal cell carcinoma (mRCC), but its effects as a first-line monotherapy are unclear. Thus, we aimed to elucidate pretreatment clinical factors that predict the prognosis of patients with mRCC receiving first-line axitinib therapy. We enrolled 63 patients with mRCC treated with axitinib as first-line therapy between Nov. 2003 and Jul. 2018. Progression-free survival (PFS) and overall survival (OS) were assessed using the Wald χ2 statistic in Cox proportional hazards regression. Median patient age was 67 (range: 25-85) years. Seven (11.1%) patients were classified as being at favorable risk, 33 (52.4%) at intermediate risk, and 23 (36.5%) at poor risk according to the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk classification system. Median follow-up duration after axitinib initiation was 14 (range: 1-72) months. Median PFS and OS were 18 months and 65 months, respectively. Cox regression analyses of clinical predictors revealed that high C-reactive protein (CRP) levels were significantly correlated with shorter PFS [hazard ratio (HR), 1.63; 95% confidence interval (CI) 1.7-4.0)], whereas spindle cells and poor IMDC risk scores were related to worse OS (HR, 2.87 and 2.88, respectively; 95% CI 1.4-11.0 and 1.1-8.5, respectively). Thus, patients with mRCC and spindle histology or poor IMDC risk scores had worse OS, and those with high CRP levels had shorter PFS in first-line axitinib treatment. Other therapies might be more suitable for initial management of such patients.

Primary pleural liposarcoma combined spindle cell lipoma of the lung.

Liposarcoma is a malignant adipose tissue tumor which mainly originates from the extremities and retroperitoneum. Primary pleural liposarcoma is very rare. Spindle cell lipoma is a rare benign adipose tissue tumor. A 66-year-old male was referred to our hospital for the evaluation of a mass-like opacity visible on chest X-ray. Computed tomography (CT) scan revealed a well-defined soft tissue mass with internal low attenuations and adjacent multiple nodules in the upper lobe of the left lung, and surgical excision was subsequently performed. Histopathological findings revealed adipose tissue with lipoblasts and spindle cells and immunohistochemical staining (IHC) revealed the tumor cells were strongly positive for CDK4 and MDM2. Histopathological examination of the small lung nodules showed spindle cell proliferation and adipose tissue without positivity for MDM2. Here, we report a rare case of primary pleural liposarcoma combined adjacent spindle cell lipoma of the lung.

Nevo de Spitz y otros tumores spitzoides en la infancia. Parte 1: aspectos clínicos, histológicos e inmunohistoquímicos / Spitz Nevus and Other Spitzoid Tumors in Children-Part 1: Clinical, Histopathologic, and Immunohistochemical Features

El nevo de Spitz es una neoplasia melanocítica de células epitelioides o fusiformes que suele aparecer en la infancia. Su naturaleza es benigna, aunque en ocasiones puede mostrar unas características difíciles de distinguir del melanoma. En las últimas décadas se han clasificado las neoplasias melanocíticas spitzoides en 3tipos: nevus de Spitz, tumor de Spitz atípico y melanoma spitzoide. El tumor de Spitz atípico hace referencia a las neoplasias melanocíticas spitzoides que tienen unas características histopatológicas atípicas insuficientes para realizar el diagnóstico de melanoma y cuyo potencial maligno, actualmente, es incierto. Nuestro objetivo es revisar los aspectos clínicos, dermatoscópicos, histopatológicos e inmunohistoquímicos de este conjunto de tumores

A Spitz nevus is a melanocytic neoplasm of epithelioid and/or spindle cells that usually appears in childhood. These lesions are by nature benign, but their features can sometimes make them difficult to distinguish from melanomas. Spitzoid melanocytic lesions have been grouped into 3 types in recent decades: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas. Atypical Spitz tumors are spitzoid melanocytic proliferations that have atypical histopathologic features that are insufficient to support a diagnosis of melanoma. The malignant potential of these lesions is at present uncertain. This review examines the clinical, dermoscopic, and histopathologic features of this group of lesions

Spindle cell proliferations of the sigmoid colon, rectum and anus: a review with emphasis on perineurioma.

A wide range of spindle cell proliferations are found uncommonly in the sigmoid colon, rectum and anus. They usually present as polyps, and include reactive lesions and benign and malignant neoplasms which may be primary or metastatic. They are less frequently described in the literature compared to those in the upper gastrointestinal tract, and may be underdiagnosed. The widespread use of sigmoidoscopy in symptomatic patients and bowel cancer screening programmes means that histopathologists must be aware of, and adopt a logical approach to, diagnosing spindle cell proliferations in biopsy and polypectomy specimens. This is particularly relevant given the strong association of some mesenchymal polyps with hereditary cancer syndromes. This review article will focus on perineurioma and the recent debate in relation to its overlap with fibroblastic polyp. The clinical, endoscopic, histological and immunohistochemical features of spindle cell proliferations which should be considered in the differential diagnosis of perineurioma will be discussed. There is also a brief reference to malignant spindle cell tumours of diagnostic importance.

Dermatofibrosarcoma protuberans: a tumor in the wide spectrum of the bland-looking spindle cell lesions of the breast.

Dermatofibrosarcoma protuberans (DFSP) is a soft tissue tumor, usually occurring as a cutaneous lesion localized to the trunk or extremities; although it has a high rate of local recurrence, its metastatic potential is very low and complete surgical excision is frequently curative. Most of the cases reported as "DFSP of the breast" are tumors arising in the subcutaneous tissue infiltrating the underlying breast parenchyma. To the best of our knowledge, only 5 cases of DFSP of the breast have been reported to date. We herein present a rare case of DFSP of the breast parenchyma in a 41-year-old female with emphasis on the diagnostic clues and the differential diagnosis with other benign and malignant spindle cell lesions of the breast.

Esophageal tuberculosis in an HIV-positive patient mimicking a spindle cell tumor / Tuberculosis esofágica en un paciente VIH-positivo simulando un tumor de células fusiformes

Tuberculosis (TB) of the esophagus is an extremely rare condition, even in immunocompromised PATIENTS: We report the case of a 24-year-old man with a past history of HIV and pulmonary tuberculosis who presented with dysphagia and a 2cm submucosal mass in the proximal esophagus. The biopsy was diagnosed as a spindle cell neoplasm in another center. Sections displayed a submucosal lesion formed by spindle and epithelioid cells, surrounded by chronic inflammation. The spindle cells were positive for S100 and CD68, but negative for cytokeratin, desmin, smooth muscle actin, ALK, CD34 and CD117. Ziehl-Neelsen stain was performed and showed many intracellular acid-fast bacilli, confirming the diagnosis of esophageal TB. This case is a reminder that esophageal TB may become manifest as a submucosal lesion and the histiocytic-granulomatous reaction may mimic a spindle cell tumor

La tuberculosis (TB) del esófago es una condición extremadamente rara incluso en pacientes inmunocomprometidos. Presentamos el caso de un varón de 24 años con historia médica de VIH y TB pulmonar, que consultó por disfagia y una masa submucosa de 2cm en el esófago proximal. La biopsia fue derivada de una institución externa como una neoplasia de células fusiformes. Los cortes mostraron una lesión submucosa formada por células fusiformes y epitelioides, rodeadas de inflamación crónica. Las células fusiformes fueron positivas para S100 y CD68, pero negativas para citoqueratina, desmina, actina de músculo liso, ALK, CD34 y CD117. Se realizó la tinción de Ziehl-Neelsen y mostró muchos bacilos intracelulares ácido-alcohol resistente, confirmando el diagnóstico de TB esofágica. Este caso es un recordatorio de que la TB esofágica puede manifestarse como una lesión submucosa y la reacción histiocítica-granulomatosa puede simular un tumor de células fusiformes

Spindle Cell Predominant Trichodiscoma or Spindle Cell Lipoma With Adnexal Induction? A Study of 25 Cases, Revealing a Subset of Cases With RB1 Heterozygous Deletion in the Spindle Cell Stroma.

In our routine and consultative pathology practices, we have noticed that a relatively high proportion of spindle cell predominant trichodiscomas demonstrate a remarkable stromal admixture of adipose tissue, which along with spindle cells, prominent collagen bundles and myxoid change closely resembles spindle cell lipoma (SCL). To clarify their possible relationship to SCL, 25 cases of trichodiscoma and fibrofolliculoma with stromal "lipomatous metaplasia" were collected and examined using immunohistochemical stains [CD34 and retinoblastoma-1 (RB1) protein] and fluorescence in situ hybridization (RB1 deletion). The patients ranged in age from 35 to 81 years (median 64 years). The male to female ratio was almost equal (14:11). All tumors with a known location were situated on the face with a special predilection for the nose. All cases were sporadic, with all patients having a single lesion and showing no clinical features of Birt-Hogg-Dubé syndrome. No case with available follow-up presented with a recurrence or an otherwise aggressive clinical course. Spindle cell stroma was immunohistochemically positive for CD34 in 16 of 20 cases, and 18 of 19 cases showed loss of RB1 staining in lesional spindle cells. Fluorescence in situ hybridization analysis detected RB1 gene heterozygous deletion in 6 of 20 cases. We conclude that despite the SCL-like appearance of the investigated cases, the majority of them supposedly represent genuine spindle cell predominant trichodiscomas with adipose tissue admixture. However, there was a subset of histopathologically indistinguishable cases with proved RB1 deletion, which likely represent SCL with trichodiscoma/fibrofolliculoma-like epithelial/adnexal induction rather than spindle cell predominant variant of trichodiscoma.

The color of skin: black diseases of the skin, nails, and mucosa.

Gradations in skin color are a consequence of differing amounts of melanin and their varying distribution. Although many darkly pigmented skin lesions are melanocytic and can be attributed to melanin content, the color of a black lesion can also be due to blood, necrotic tissue, or exogenous pigment. The source, pattern, and distribution of the color in black lesions usually offer important insight into its etiology. This contribution reviews conditions that can take on a black color, discussing the cause of the hue and any additional impact sun exposure may have.

Cutaneous Spindle Cell Neoplasms: Pattern-Based Diagnostic Approach.

CONTEXT: - Spindle cell neoplasms arising in the skin comprise a heterogeneous group of tumors with divergent lineages. Cutaneous spindle cell neoplasms are relatively common and present surgical pathologists with diagnostic challenges. Recognition of their histopathologies is important for correct diagnosis and management. The current review presents a pattern-based diagnostic approach to common cutaneous spindle cell neoplasms that often cause diagnostic difficulties. OBJECTIVE: - To provide a useful guide for diagnosis of cutaneous spindle cell neoplasms. DATA SOURCES: - PubMed (US National Library of Medicine) reports and the authors' personal experiences are reviewed. CONCLUSIONS: - The authors briefly summarize the histologic features and differential diagnoses of common cutaneous spindle cell neoplasms.

Genomic Fusions in Pigmented Spindle Cell Nevus of Reed.

Recent molecular studies of spitzoid neoplasms have identified mutually exclusive kinase fusions involving ROS1, ALK, RET, BRAF, NTRK1, MET, and NTRK3 as early initiating genomic events. Pigmented spindle cell nevus (PSCN) of Reed is a morphologic variant of Spitz and may be very diagnostically challenging, having histologic features concerning for melanoma. Their occurrence in younger patients, lack of association to sun exposure, and rapid early growth phase similar to Spitz nevi suggest fusions may also play a significant role in these lesions. However, to date, there is little data in the literature focused on the molecular characterization of PSCN of Reed with next-generation sequencing. We analyzed a total of 129 melanocytic neoplasms with RNA sequencing including 67 spitzoid neoplasms (10 Spitz nevi, 44 atypical Spitz tumors, 13 spitzoid melanomas) and 23 PSCN of Reed. Although only 2 of 67 (3.0%) of spitzoid lesions had NTRK3 fusions, 13 of 23 (57%) of PSCN of Reed harbored NTRK3 fusions with 5' partners ETV6 (12p13) in 2 cases and MYO5A (15q21) in 11 cases. NTRK3 fusions were confirmed with a fluorescent in situ hybridization break-apart probe. The presence of a NTRK3 fusion correlated with younger age (P=0.021) and adnexal extension (P=0.001). Other minor fusions identified in PSCN of Reed included MYO5A-MERTK (2), MYO5A-ROS1, MYO5A-RET, and ETV6-PITX3 leading to a total of 78% with fusions. Our study suggests that the majority of PSCN of Reed are the result of genomic fusions, and the most frequent and characteristic genomic aberration is an NTRK3 fusion.

Melanocytic Myxoid Spindle Cell Tumor With ALK Rearrangement (MMySTAR): Report of 4 Cases of a Nevus Variant With Potential Diagnostic Challenge.

Melanocytic tumors rarely display extensive dermal myxoid deposits except in the myxoid variant of melanoma. We describe in 4 patients the unusual association of morphologic and genetic features. All cases occurred in males and were located on the limbs or proximal girdle area. Age at diagnosis ranged from 8 to 47 years. Size ranged from 6 to 11 mm. Microscopic analysis showed compound, but mainly dermal melanocytic nevi, all presenting a deep dermal expansion with fascicules of amelanotic spindled cells floating in a myxoid background. Cytologic atypia and mitotic activity were low. The superficial portion was either of spitzoid or nevoid cytology with a limited junctional component. In the initial case, the dermal myxoid component was predominant with rare, barely visible, superficial melanocytic nests. This peculiar morphology was responsible for a delayed diagnostic, which required an extensive panel of antibodies ruling out most, potentially myxoid, soft tissue tumors. We later observed the presence of similar, but more limited, dermal morphologic features in 3 other cases. Immunohistochemistry in the deep myxoid areas was melanA, ALK, SOX10, and MiTF. Molecular studies confirmed the ALK rearrangement by an ALK break-apart fluorescence in situ hybridization technique and by RNA sequencing. The latter identified 4 different 5'-fusion partners. Two gene fusions were undescribed: FBXO28(e2)-ALK(e19) and NPAS2(e2)-ALK(e19), and 2 previously described: TPM3(e7)-ALK(e20) and PPFIBP1(e9)-ALK(e19). No relapse or metastatic evolution was seen during follow-up (3 to 24 mo). We denominated this potentially challenging new variant of compound nevus linked to a kinase fusion: Melanocytic Myxoid Spindle Cell Tumor with ALK Rearrangement.

Cytogenetics of Spindle Cell/Pleomorphic Lipomas: Karyotyping and FISH Analysis of 31 Tumors.

BACKGROUND: Spindle cell/pleomorphic lipomas are benign tumors. Here, we present our cytogenetic data on 31 such tumors. MATERIALS AND METHODS: G-banding chromosome analysis and (in selected cases) fluorescence in situ hybridization (FISH) using probes for FOXO1, RB1, and HMGA2 were performed. RESULTS: Rearrangements of chromosome 13 were found in 58% of tumors. Chromosomes 6, 1, 12, and 11 were also involved in 42%, 26%, 26%, and 23% of tumors, respectively. FISH analysis showed heterozygous deletion of RB1 in seven samples with chromosome 13 aberrations. In four of them, FOXO1 was also deleted. In two tumors with 12q15 rearrangements, FISH confirmed that HMGA2 was targeted. CONCLUSION: Structural rearrangements of 13q or losses of an entire chromosome 13 are the most common cytogenetic aberrations in spindle cell/pleomorphic lipomas. However, cytogenetic variation exists similarly to what is found in other lipomas, suggesting that various pathways may be responsible for tumorigenesis.

Fibromixolipoma dendrítico infraclavicular: en el límite entre el lipoma de células fusiformes y el tumor fibroso solitario / Dendritic infraclavicular fibromyxolipoma: at the boundary between spindle cell lipoma and solitary fibrous tumour

El fibromixolipoma dendrítico (FMLD) es un tumor de partes blandas recientemente descrito, muy poco frecuente, de los cuales tan solo hay 27 casos reseñados en la literatura, ninguno con recidivas y/o metástasis tras su extirpación. Histológicamente está constituido por una proliferación de células pequeñas, estrelladas o fusiformes, en un estroma mixoide con abundantes haces de colágeno y áreas dispersas de tejido adiposo maduro. Dichas células proliferantes se tiñen, de forma característica, con CD34 y bcl-2, y muestran, entre otras aberraciones citogenéticas, deleción en la región 13q14.3. Presentamos un caso de FMLD localizado en la región infraclavicular, en un hombre de 69 años que refiere una masa de 5cm de diámetro, circunscrita y no dolorosa, de varios años de evolución, que tras su extirpación y durante un periodo de seguimiento de 2 años no ha mostrado recidivas ni metástasis. Describimos las características clinicopatológicas de esta entidad y sus diagnósticos diferenciales, haciendo una revisión amplia de la literatura (AU)

Dendritic fibromyxolipoma (DFML) is a rare soft tissue tumor recently described with only 27 cases reported in the literature. None of them have shown recurrence or metastasis after excision. Histologically it is composed of small stellate or spindle cells in a myxoid stroma with abundant collagen bundles mixed with mature adipose tissue. The proliferating cells typically show immunoexpression positive for CD34 and bcl-2. A cytogenetic analysis reveals deletion involving 13q14.3 region. We describe the first reported case to date located in the infraclavicular region. A 69 year old male with a painless mass well circumscribed and 5cm in size of several years of evolution, that after excision (2 years ago) he has not shown signs of recurrence or metastasis. This study reflects the clinicopathological features, differential diagnosis and a review of the literature of the DFML (AU)