A 2-tiered histologic grading scheme for canine cutaneous mast cell tumors (MCTs) is based on morphologic characteristics of neoplastic cells, including karyomegaly, multinucleation, nuclear ...pleomorphism, and mitotic figures. Aspirates from MCTs may provide the same information more quickly, inexpensively, and less invasively. This study used these criteria to develop a cytologic grading scheme for canine MCTs to predict outcome. Three anatomic pathologists graded histologic samples from 152 canine MCTs. Three clinical pathologists evaluated aspirates from these masses using similar criteria. A cytologic grading scheme was created based on correlation with histologic grade and evaluated with a kappa statistic. Survival was evaluated with Kaplan-Meier survival curves. Cox proportional hazards regression was used to estimate hazard ratios for tumor grades and individual grading components. Simple logistic regression tested for relationships between risk factors and mortality. The cytologic grading scheme that best correlated with histology (kappa = 0.725 ± 0.085) classified a tumor as high grade if it was poorly granulated or had at least 2 of 4 findings: mitotic figures, binucleated or multinucleated cells, nuclear pleomorphism, or >50% anisokaryosis. The cytologic grading scheme had 88% sensitivity and 94% specificity relative to histologic grading. Dogs with histologic and cytologic high grade MCTs were 39 times and 25 times more likely to die within the 2-year follow-up period, respectively, than dogs with low grade MCTs. High tumor grade was associated with increased probability of additional tumors or tumor regrowth. This study concluded that cytologic grade is a useful predictor for treatment planning and prognostication.
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.
Mast cell sarcoma: clinical management Weiler, Catherine R; Butterfield, Joseph
Immunology and allergy clinics of North America,
05/2014, Letnik:
34, Številka:
2
Journal Article
Recenzirano
Mast cell sarcoma is a disorder that results in abnormal mast cells as identified by morphology, special stains, and in some publications, c-kit mutation analysis. It affects animal species such as ...canines more commonly than humans. In humans it is a very rare condition, with variable clinical presentation. There is no standard therapy for the disorder. It can affect any age group. It is occasionally associated with systemic mastocytosis and/or urticaria pigmentosa. The prognosis of mast cell sarcoma in published literature is very poor in humans.
Purpose: The purpose of this study was to determine the objective response rate (ORR) following treatment of canine mast cell tumors
(MCT) with toceranib phosphate (Palladia, SU11654), a kinase ...inhibitor with both antitumor and antiangiogenic activity through
inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRβ. Secondary objectives were to determine biological
response rate, time to tumor progression, duration of objective response, health-related quality of life, and safety of Palladia.
Experimental Design: Dogs were randomized to receive oral Palladia 3.25 mg/kg or placebo every other day for 6 weeks in the blinded phase. Thereafter,
eligible dogs received open-label Palladia.
Results: The blinded phase ORR in Palladia-treated dogs ( n = 86) was 37.2% (7 complete response, 25 partial response) versus 7.9% (5 partial response) in placebo-treated dogs ( n = 63; P = 0.0004). Of 58 dogs that received Palladia following placebo-escape, 41.4% (8 complete response, 16 partial response) experienced
objective response. The ORR for all 145 dogs receiving Palladia was 42.8% (21 complete response, 41 partial response); among
the 62 responders, the median duration of objective response and time to tumor progression was 12.0 weeks and 18.1 weeks,
respectively. Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated nonresponders
( P = 0.030). There was no significant difference in the number of dogs with grade 3/4 (of 4) adverse events; adverse events
were generally manageable with dose modification and/or supportive care.
Conclusions: Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine
planned treatment breaks. This clinical trial further shows that spontaneous tumors in dogs are good models to evaluate therapeutic
index of targeted therapeutics in a clinical setting.
Mast cell sarcoma (MCS) is a rare form of mastocytosis characterized by the presence of solid tumor(s) comprising malignant mast cells that harbor destructive infiltration capability and metastatic ...potential. Here, we present an extensive literature review and report on 23 cases of MCS, including 3 new cases from the French National Reference Center for Mastocytosis. From our analysis, it appears that MCS can occur at any age. It can manifest de novo or, to a lesser extent, may evolve from a previously established mastocytosis. Bone tumor is a frequent manifestation, and symptoms of mast cell activation are rare. Histological diagnosis can be difficult because MCS is frequently composed of highly atypical neoplastic mast cells and can thus mimic other tumors. Unexpectedly, the canonical KIT D816V mutation is found in only 21% of MCS; therefore, complete KIT gene sequencing is required. The prognosis of patients with MCS is poor, with a median survival time of less than 18 months, and progression to mast cell leukemia is not unusual. Because conventional chemotherapies usually fail, the role of targeted therapies and bone marrow transplantation warrants further investigation in such aggressive neoplasms.
To assess the usefulness of histologic evaluation of surgical margins to predict local recurrence of cutaneous malignant tumors in dogs and cats treated by means of surgical excision.
Prospective ...case series.
40 dogs and 20 cats.
60 surgically excised tumors (20 soft tissue sarcomas STSs, 20 mast cell tumors MCTs, and 20 carcinomas) were examined histologically. Margins were classified as clean, close, or infiltrated; histologic grade was assessed in STSs and MCTs. Recurrence rates and recurrence-free intervals (RFIs) during a 24-month follow-up period were recorded, and method accuracy was calculated.
Surgical margins were clean in 29 of 60 (48%) tumors, close in 11 (18%), and infiltrated in 20 (33%). Tumors recurred in 27 of 60 (45%) animals, with a mean ± SD RFI of 229 ± 173 days. Recurrence rates for animals that had tumors with infiltrated (16/20) or close (8/11) margins were significantly higher than recurrence rate for animals that had tumors with clean margins (3/29). Margin classification was a significant predictor of RFI. Accuracy of the method to predict recurrence was 94% for carcinomas, 87% for STSs, and 76% for MCTs.
Histologic assessment of margin status was useful for predicting local recurrence of cutaneous malignant tumors in dogs and cats treated by means of excision alone. Method accuracy varied among tumor types and grades. Recurrence times suggested postsurgical follow-up should continue for ≥ 2 years. Results were similar for animals with infiltrated and close tumor margins, and careful postsurgical management is recommended for both.
Mast cell sarcoma (MCS) is an extremely rare neoplasm with a clinically aggressive course. Because of its rarity, its morphologic and molecular characteristics are still not well defined. We report a ...case of a 15-year-old girl with MCS of the temporal bone extending into the posterior fossa creating a mass effect. The lesion mimicked a histiocytic neoplasm morphologically, but showed a novel KIT missense mutation, L799F (2395 C>T). The KIT D816V mutation is frequently found in systemic mastocytosis, but it has not been documented in the few reported human MCS cases. However, 1 reported case of MCS has shown a different alteration in the KIT gene. Our case is the first MCS case with L799F mutation, located between the catalytic loop (790 to 797) and the activation loop (810 to 837) of the KIT gene, and only the second case of MCS with KIT mutation documented in the literature. Proximity of the L799F mutation to the enzymatic region of the KIT tyrosine kinase domain may induce resistance to tyrosine kinase inhibitors.
Mast cell diseases comprise a spectrum of disorders including cutaneous mastocytosis, indolent or aggressive systemic variants including leukemia, and unifocal tumor formations such as benign ...extracutaneous mastocytoma or aggressive mast cell sarcoma (MCS). Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase activity, typically exhibiting point mutation in codon 816. MCS is an exceedingly rare clinicopathologic entity characterized by a unifocal accumulation of neoplastic mast cells that grow in a locally destructive manner. We report a case in a 2-year-old boy who was initially diagnosed at 8 months of age with atypical cutaneous mastocytoma of the right ear with subsequent aggressive, destructive growth pattern; features that were most consistent with MCS. So far, MCS has been documented in the literature in at least 6 human cases. To the best of our knowledge, our case represents the first MCS in an infant. Thorough multimodal approach with strict follow-up is relevant in appropriately diagnosing this rare entity, particularly in differentiating this lesion from other neoplasms that are more likely to occur in infancy.
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