Mast Cell Sarcoma Mimicking Lymphoma or Metastatic Disease on 18 F-FDG PET/CT.

ABSTRACT: We report an 18 F-FDG PET/CT scan of a 47-year-old man diagnosed with diffuse mast cell sarcoma with lymph node, bone, liver, spleen, and lung involvement. This interesting image should remind colleagues to consider mast cell sarcoma as a rare differential diagnosis in patients with multiple, intensely hypermetabolic lesions in various organs and lymph nodes.

Mast cell sarcoma: clinicopathologic and molecular analysis of 10 new cases and review of literature.

Mast cell sarcoma (MCS) is an exceedingly rare form of mastocytosis characterized by invasive malignant mast cell growth and metastatic potential. Diagnosis of MCS is very challenging due to its marked morphologic variations and significant immunophenotypic overlap with other neoplasms. In this study, we undertook an extensive study of 10 cases of MCS from our series, with review of additional 24 cases from the literature, to better clarify the clinicopathologic and molecular features of MCS. From the analyses of our 10 cases, MCS equally involved males and females with a median age of 54.5 years (range 1-63). The bone was the most common site of involvement, as noted in 9/10 of cases. Two patients had prior germ cell tumors (mediastinal germ cell tumor and ovarian dysgerminoma), and concurrent systemic mastocytosis was noted in one of nine patients. Serum tryptase levels were elevated in 6/7 of patients, and 3/9 of patients had mast cell activation symptoms. Morphologically, the tumor cells were typically large and pleomorphic with frequent reactive eosinophils. By immunohistochemical staining, MCS consistently expressed CD43 (8/8), CD117 (10/10), and mast cell tryptase (10/10), as well as CD13 (3/3) and CD33 (10/10), with variable positivity of CD2 (1/9), CD25 (4/9), CD30 (5/8), and CD68 (5/9). Notably, KIT D816V was not detected in nine cases in our study, although two cases had other mutations of KIT gene. Seven out of eight patients received chemotherapy with or without radiotherapy. However, the response was poor, and four out of eight patients died within a median follow-up interval of five months. Taken together, there are no standardized therapeutic regimens available for MCS at this time, and the prognosis is dismal. Therefore, it is critical to further investigate and characterize this rare entity, with the hope of improving diagnostic accuracy and providing more effective, targeted therapies.

Case report of a clinically indolent but morphologically high-grade cutaneous mast cell tumor in an adult: Atypical cutaneous mastocytoma or mast cell sarcoma?

We present a case of an adult male with a solitary mast cell tumor of the skin with unusual nuclear pleomorphism and mitotic activity. The tumor was excised, recurred within 2 years, was reexcised after 4 years and did not recur >6 years after diagnosis. The tumor showed progressive cytonuclear atypia and a high mitotic and proliferation rate by Ki67-staining from the onset. No KIT mutations were identified in the tumor and bone marrow. Serum tryptase levels and a bone marrow aspirate and trephine biopsy were normal. Although the histomorphology of the skin tumor was consistent with mast cell sarcoma, the clinical behavior without systemic progression argued against this diagnosis. The tumor was finally considered as atypical mastocytoma, borderline to mast cell sarcoma. Currently, the patient is in close follow-up and still in complete remission.

Immunohistochemical Expression of Vascular Endothelial Growth Factor as a Prognostic Marker for Canine Mast Cell Tumors.

Strong to moderate vascular endothelial growth factor (VEGF) expression may be a negative prognostic factor in canine mast cell tumors (MCTs). This study set out to determine the prognostic value of combined analysis of VEGF-A immunoreactivity, clinical presentation, patient staging, and tumor histologic grade in canine MCTs. In this study, intense VEGF staining was significantly associated with decreased survival (P = .025). Immunohistochemical expression of VEGF is not routinely employed as a prognostic factor in canine MCT workup. However, results of this study support the inclusion of this marker in the MCT prognostic panel. Investigation of VEGF expression may assist in the development of anti-VEGF drugs.

Mastocitoma felino. Reporte de caso / Feline mastocytoma. Case report

RESUMEN Los mastocitomas son tumores originarios de los mastocitos que usualmente afectan a los perros y los gatos. Pueden llegar a tener un comportamiento benigno, sin embargo, esto dependerá del grado de la neoplasia y su estadiaje. En felinos, clínicamente se han descrito dos patrones: visceral y cutáneo, de los cuales el cutáneo es el más frecuente, llegando a causar metástasis a órganos adyacentes e incluso afectar el bazo y/o intestino en estadios más diferenciados. Se presenta un caso de mastocitoma felino correspondiente a un ejemplar mestizo con cuadro clínico de inicio de más de dos meses de evolución, consistente en la aparición de una placa alopécica ulcerada y elevada en región interescapular, acompañada de prurito que presentó resolución espontánea. Mediante el curso clínico se imnunizó contra el virus de la rabia, posteriormente, se observó la aparición de una lesión nodular subcutánea de características inusuales de 2cm de diámetro. Acorde con el tiempo de evolución y el antecedente vacunal se decidió la realización de biopsia y resección quirúrgica. El reporte de la biopsia confirmó diagnóstico de mastocitoma grado histológico 3 de Patnaik, teniendo en cuenta las características histológicas, estructurales y su comportamiento clínico. Se realizó seguimiento del caso pasados ocho meses, donde se evidenció mejoría del cuadro clínico, sin aparición de nueva masa sugestiva de neoplasia, sin hallazgos de metástasis a otras estructuras, con cicatrización exitosa de herida quirúrgica y evolución satisfactoria.

ABSTRACT Mast cells are tumors originating from mast cells which usually affect cats and dogs. They may have benign behavior, however, this will depend on the degree of the neo-plasm and its staging. In cats, two patterns have been described clinically: visceral and cutaneous, of which the cutaneous form is the most frequent, reaching metastasis to adjacent organs and even affecting the spleen and / or intestine in more differentiated stages. A case of a mastocytoma is presented, a feline corresponding to a mongrel specimen with a clinical picture of onset of more than two months of evolution, consisting of the appearance of an allopecal plaque, ulcerated and elevated in the interscapular region, accompanied by pruritus that presented spontaneous resolution. Through the clinical course, he was immunized against the rabies virus, later the appearance of a nodular lesion of unusual subcutaneous characteristics, 2 cm in diameter, was observed. According to the evolution time and the vaccination history, it was decided to perform a biopsy and surgical resection. The biopsy report confirmed the diagnosis of Patnaik's histological grade 3 mastocytoma, taking into account the histological and structural characteristics and its clinical behavior. The case was followed up after eight months, where an improvement in the clinical picture was evident, without the appearance of a new mass suggestive of neoplasia, without metastatic findings to other structures, with successful healing of the surgical wound and satisfactory evolution.

Use of indirect computed tomography lymphangiography to determine metastatic status of sentinel lymph nodes in dogs with a pre-operative diagnosis of melanoma or mast cell tumour.

Canine melanomas and mast cell tumours (MCTs) frequently metastasize to lymph nodes, worsening prognosis compared with dogs without metastasis. Sentinel lymph node (SLN) evaluation is more specific than evaluation of the lymph node closest to the tumour, which may not be the draining lymph node. Computed tomography lymphangiography (CTL) allows for SLN identification and one study of canine mammary tumours found that CTL was able to assist in determination of the metastatic status of inguinal SLNs prior to extirpation and histopathology. The objective of the present study was to evaluate CTL for use in determining metastasis to the SLN in dogs with a pre-operative diagnosis of melanoma or MCT in various locations by correlating CTL findings with histopathology. The hypothesis was that CTL would not be able to determine the metastatic status of lymph nodes, based on author experience. Dogs were prospectively enrolled and underwent CTL and subsequent SLN extirpation. Histopathology results for the primary tumour, SLN, and additional extirpated lymph nodes were recorded. Fifteen dogs were enrolled and 21 SLN were evaluated. The SLN enhancement pattern (heterogeneous, homogenous or peripheral) was not associated with metastasis, nor was the attenuation value at 1 minute, 5 minutes, or the change in attenuation value. No correlation was found between CTL findings and metastatic status of SLNs. Based on these results, CTL alone cannot be used to diagnose SLN metastasis. Extirpation of the SLN with histopathology is recommended to diagnose lymph node metastasis in dogs with melanoma and MCT.

Histologically low-grade, yet biologically high-grade, canine cutaneous mast cell tumours: A systematic review and meta-analysis of individual participant data.

Low-grade canine cutaneous mast cell tumour (cMCT) with metastasis at the time of treatment is uncommonly reported, with few studies focusing on this specific clinical entity. The specific objective of this study was to systematically review the veterinary literature and perform a meta-analysis summarizing the clinical presentation, treatments reported and clinical outcomes from dogs with histologically low-grade cMCT and metastasis present at initial treatment. A total of 980 studies were screened with eight publications providing data on 121 dogs ultimately included. The most common treatments were surgery with adjuvant chemotherapy in 83/121 (69%) dogs; combined surgery, radiation and chemotherapy in 17/121 (14%) dogs; chemotherapy alone in 12/121 (10%) dogs and surgery alone in 7/121 (6%) dogs. Dogs with distant metastasis (n = 22) experienced significantly shorter survival compared with those with regional lymph node (RLN) metastasis (n = 99; median 194 vs 637 days; P < .01). Two variables were significantly associated with increased risk of death: presence of distant (vs RLN) metastasis (hazard ratio = 2.60; P < .01) and not receiving surgery as a component of treatment (hazard ratio = 3.79; P < .01). Risk of bias was judged to be low in terms of selection and performance bias but high in terms of detection and exclusion bias. In conclusion, dogs with cMCT and RLN metastasis can be expected to live significantly longer than those with distant metastasis, and surgery appears to have a role in extending survival of metastatic low-grade cMCT.

Recurrent gene mutations detected in canine mast cell tumours by next generation sequencing.

Genetic causes of canine mast cell tumours (MCTs), except for mutations in the KIT gene detected in some MCTs, are generally unknown. We used whole exome sequencing to reveal mutation spectra in canine MCTs. We detected somatic mutations in 87 genes including 10 genes recognized as human cancer drivers. Besides KIT, 14 other genes were recurrently mutated. Subsequently, we performed next generation sequencing of a panel of 50 selected genes in additional MCT samples. In this group, the most frequently altered gene was GNB1 showing a recurrent dinucleotide substitution at position of Gly116 in 30% of the MCT samples (n = 6/20) and Ile80 substitution accompanied by a splice region mutation in one case. We extended the study by analysis of the above mentioned GNB1 regions in additional MCT samples by Sanger sequencing, and assessed the overall prevalence of GNB1 mutations to 17.3% (n = 14/81), which is similar to the prevalence of KIT alterations. Our results indicate that GNB1 mutations are probably involved in canine MCT pathogenesis in both cutaneous and subcutaneous MCT cases. As opposed to KIT alterations, the presence of GNB1 mutations did not negatively affect survival times, and our data even showed a trend towards positive prognosis. If our results are confirmed in a larger number of MCTs, an extension of molecular testing of canine MCTs by GNB1 analysis would help to refine the molecular stratification of MCTs, and become useful for targeted treatment strategies.

A systematic review of surgical margins utilized for removal of cutaneous mast cell tumors in dogs.

BACKGROUND: Traditionally, wide lateral surgical margins of 3 cm and one fascial plane deep have been recommended for resection of canine cutaneous mast cell tumor (MCT). Several studies have been published assessing surgical margins of less than this traditional recommendation. The objective of this systematic review was to determine if resection MCT with lateral surgical margins < 3 cm results in low rates of incomplete resection and local tumor recurrence. Systematic searches of digital bibliographic databases were performed with two authors (AR & LES) screening abstracts to identify relevant scientific articles. Studies regarding surgical treatment of dogs with cutaneous MCT were reviewed. Data abstraction was performed and the quality of individual studies and the strength of the body of evidence for utilization of surgical margins < 3 cm for removal of MCTs was assessed. RESULTS: From the initial 78 citations identified through the database searches, four articles were retained for data abstraction after both relevance screenings were performed. Two studies were retrospective observational studies, one was a prospective case series and one was a prospective clinical trial. Assessment of the quality level of the body of evidence identified using the GRADE system was low. Excision of MCT at 2 cm and 3 cm was associated with comparably low rates of incomplete excision and recurrence. CONCLUSIONS: Despite the low quality of the overall body of evidence, a recommendation can be made that resection of canine cutaneous MCTs (< 4 cm) of Patnaik grade I and II with 2 cm lateral margins and 1 fascial plane deep results in low rates of incomplete excision and local tumor recurrence.

Phosphorylated KIT as a predictor of outcome in canine mast cell tumours treated with toceranib phosphate or vinblastine.

Canine cutaneous mast cell tumour (MCT) is the most common malignant skin tumour in dogs and can exhibit variable biologic behaviour. Dysregulated signalling through the receptor tyrosine kinase (RTK) KIT can promote cell proliferation and survival, and assessment of its dysregulation via detection of activating c-kit gene mutations or assessment of KIT protein localization is associated with multiple features of malignancy. The aim of the current study was to use a previously validated immunohistochemical (IHC) assay to directly measure phosphorylated KIT (pKIT) in order to investigate its association with other established prognostic markers, response to therapy, progression free interval (PFI) and overall survival time (OST) in dogs treated medically for measurable MCT. Tumour tissue from 74 dogs enrolled in a prospective study comparing toceranib and vinblastine for MCT treatment were evaluated for pKIT immunoreactivity. pKIT was variably expressed, with some degree of positivity observed in 49/74 cases (66%). pKIT immunoreactivity was significantly associated with aberrant KIT localization, high mitotic index and high histologic grade. On univariate analysis, pKIT immunoreactivity predicted shorter PFI and OST in the entire patient population as well as shorter PFI in the toceranib treated group, and was the sole predictive factor for OST upon multivariate analysis, while mitotic index was the sole independent predictive factor for PFI. These results demonstrate that IHC detection of pKIT correlates with several features of aggressive behaviour, and may confer information that is complementary to other prognostic factors. However, the role of pKIT in predicting outcome needs to be studied further before recommendations can be made for its routine use.

Treating the locoregional lymph nodes with radiation and/or surgery significantly improves outcome in dogs with high-grade mast cell tumours.

High-grade canine mast cell tumours (HG-MCT) have a high rate of locoregional relapse. In this study, dogs with HG-MCT treated with radiation therapy (RT) were retrospectively evaluated to determine the benefit associated with treating the locoregional lymph nodes (LNs). Forty-two dogs were included. Variables assessed for association with overall survival (OS) and progression-free survival (PFS) included WHO stage, tumour location and size, LN irradiation (prophylactic, therapeutic or none), LN treatment (yes or no), LN status at RT (metastatic or nonmetastatic) and RT intent (definitive vs palliative). Lower-stage disease at irradiation was significantly associated with prolonged median PFS (425 vs 125 days for stage 0 vs 1-4), and OS (615 vs 314 days for stage 0 vs 1-4). Having any LN treatment and definitive RT were both significantly associated with prolonged OS. In order to evaluate the role of LN irradiation, dogs were divided into subgroups: (a) stage 0 at irradiation with no LN treatment (n = 14), (b) stage 0 at irradiation with prophylactic LN irradiation (n = 6), (c) stage 0 at irradiation but previously stage 2 (n = 5) and (d) stage >0 at irradiation (n = 17). Prophylactic LN irradiation significantly prolonged PFS (>2381 vs 197 days; group B vs A). Interestingly, dogs that were stage 2 and had LN treatment (C) had prolonged OS vs dogs with negative LNs and no LN treatment (A) (1908 vs 284 days; P = .012). This study confirms that prophylactic and therapeutic LN irradiation in dogs with HG-MCT is beneficial and improves outcome.

Retrospective study of canine cutaneous tumors in Japan, 2008-2017.

Cutaneous tumors are commonly found in dogs. To date, few studies have investigated the epidemiology of canine cutaneous tumors in Asian countries. The present study aims to report the prevalence of canine cutaneous tumors in Japan, and assess the association of breed, age, sex, and anatomical locations with the development of common tumor types. A total of 1,435 cases of cutaneous tumors were examined, of which 813 (56.66%) cases were malignant, and 622 (43.34%) were benign. Soft tissue sarcomas (18.40%), mast cell tumor (16.24%), lipoma (9.69%), hair follicle tumors (9.34%), and benign sebaceous tumors (8.50%) outnumbered the other tumor types. Tumors were commonly found on the head (13.87%), hindlimb (10.52%), forelimb (8.01%), chest (5.78%), and neck (5.57%). The risk of developing cutaneous tumors increased significantly in dogs aged 11-year and above (P<0.001). Mixed-breed dogs (14.63%), Miniature Dachshund (9.90%), and Labrador Retriever (8.01%) were the three most presented breeds; while Boxer, Bernese Mountain Dog, and Golden Retriever had an increased risk of cutaneous tumor development in comparison to mixed-breed dogs (P<0.05). Epidemiological information from the present study will serve as a useful reference for regional veterinarians to establish a preliminary diagnosis of canine cutaneous tumors.