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.

Diagnostic accuracy of pre-treatment biopsy for grading cutaneous mast cell tumours in dogs.

Mast cell tumours (MCTs) are common tumours of the canine skin, and are estimated to represent up to 20% of all skin tumours in dogs. Tumour grade has a major impact on the incidence of local recurrence and metastatic potential. In addition to helping the clinician with surgical planning, knowledge of the tumour grade also assists in proper prognostication and client education. For pre-treatment biopsies to be useful, there must exist a high level of correlation between the histopathological grade obtained from the pre-treatment biopsy and the actual histopathological grade from the excisional biopsy. The aim of this study was to determine concordance of tumour grade between various biopsy techniques (wedge, punch, needle core) and the "gold standard" excisional biopsy method. We found an overall concordance rate of 96% based on the Patnaik grading system, and an overall concordance rate of 92% based on the Kiupel grading system. The accuracy of the various biopsy techniques (wedge, punch and needle core) when compared with excisional biopsy was 92%, 100% and 100%, respectively, based on the Patnaik grading system, and 90%, 95% and 100%, respectively, based on the Kiupel grading system. Of the cases with discordant results, the pre-treatment biopsies tended to underestimate the grade of the tumour. Based on these results, we conclude that pre-treatment biopsies are sufficiently accurate for differentiating low-grade from high-grade MCTs, regardless of biopsy technique or tumour location.

The first report of human primary thoracic spine mast cell sarcoma: a case report.

In this report, we present a 53-year-old woman with primary mast cell sarcoma of the thoracic spine vertebrae. Mast cell sarcoma is an aggressive and rare cancer. To date, no cases of primary mast cell sarcoma have been reported in the spinal vertebrae. The patient initially presented with a 1-month history of pelvic and abdominal pain. Inconclusive gynecological evaluation resulted in a CT of the abdomen and pelvis, demonstrating a destructive lesion centered at the 11th thoracic vertebral body. The patient underwent a two-stage spine operation for T11 corpectomy and T7-L3 posterior spinal fusion. Histopathological, immunohistochemical, and flow cytometry studies of the resection specimens showed the tumor to be mostly composed of CD117-positive and mast cell tryptase-positive cells with features consistent with mast cell sarcoma. This is the first reported case of primary vertebral mast cell sarcoma, which may mimic other destructive lesions of the spine including osteomyelitis, vertebral tuberculosis, or plasmacytoma.
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Intramuscular mast cell tumors in 7 dogs.

Mast cell tumors (MCTs) are commonly encountered in dogs and have been reported in cutaneous, conjunctival, oral mucosal, and gastrointestinal locations, but not in an intramuscular location. Medical records at 2 referral centers in the UK were examined to find cases of MCTs in this location. Seven dogs were identified as having an intramuscular MCT by a combination of fine-needle aspirate cytology and computed tomography or ultrasound. None of the dogs had evidence of local lymph node metastasis. Six dogs had no evidence of distant metastasis and surgery was carried out as the primary treatment option. Three of those dogs also had adjunctive chemotherapy due to a high Ki67 value or high mitotic index. All 6 dogs that had had surgery were alive at follow-up with a minimum elapsed time of 7 months. One dog had a course of chemotherapy due to the location, size, and evidence of biological activity of the tumor and died 23 days afterwards. The prognosis of intramuscular mast cell tumors appears to be favorable in most cases.

Tumeurs à mastocytes intramusculaires chez sept chiens. Les tumeurs à mastocytes (MCT) sont couramment observées chez les chiens et elles sont signalées à des emplacements cutanés, conjonctivaux, gastrointestinaux et dans les muqueuses orales, mais non dans des régions intramusculaires. Les dossiers médicaux de deux centres spécialisés du Royaume-Uni ont été examinés afin de trouver des cas de MCT à cet endroit. Sept chiens ont été identifiés comme ayant un MCT intramusculaire en utilisant une combinaison de cytologie par aspiration à l'aiguille fine et de tomodensitométrie ou d'échographie. Aucun des chiens ne présentait des signes de métastase des ganglions lymphatiques locaux. Six chiens ne manifestaient aucun signe de métastase distante et la chirurgie a été réalisée comme option de traitement primaire. Trois de ces chiens ont aussi subi une chimiothérapie d'appoint en raison d'une valeur élevée de Ki67 ou d'un indice mitotique élevé. Les six chiens qui avaient subi la chirurgie étaient vivants au suivi avec un délai écoulé de 7 mois. Un chien a subi un traitement de chimiothérapie en raison de l'emplacement, de la taille et de signes d'activité biologique de la tumeur et est mort 23 jours plus tard. Le pronostic de tumeurs à mastocytes intramusculaires semble être favorable dans la plupart des cas.(Traduit par Isabelle Vallières).

Intranasal mast cell tumor in the dog: A case series.

The medical records of 4 dogs with histologically confirmed intranasal mast cell tumors (MCTs) were retrospectively evaluated to determine their biological behavior. Information on signalment, presenting clinical signs, tumor grade, treatment administered, and survival times was obtained from the medical record. All 4 patients had high grade tumors and received chemotherapy. Survival times ranged from 27 to 134 days. All 4 dogs showed signs of local or distant disease progression, suggestive of an aggressive behavior of intranasal MCTs.

Tumeur mastocytaire intranasale chez le chien : une série de cas. Les dossiers médicaux de quatrechiens qui avaient eu des tumeurs mastocytaires intranasales confirmées par histologie ont été rétrospectivement évalués afin de déterminer leur comportement biologique. Des renseignements sur le signalement, les signes cliniques de présentation, le grade de la tumeur, le traitement administré et les temps de survie ont été obtenus dans le dossier médical. Les quatre patients avaient des tumeurs de grade élevé et ont reçu de la chimiothérapie. Les temps de survie ont varié de 27 à 134 jours. Les quatre chiens ont manifesté des signes de progression locale ou distante de la maladie, suggérant un comportement agressif des tumeurs mastocytaires intranasales.(Traduit par Isabelle Vallières).

Presumptive primary pulmonary mast cell tumor in 2 dogs.

Two dogs were presented, each with a large solitary pulmonary mass, and cytology confirmed mast cell tumor (MCT) in each dog. One dog was euthanized following diagnosis. Thoracic computed tomography scan and exploratory thoracotomy of the second dog revealed a right pulmonary mass that would require a radical lung resection. The patient was euthanized and histopathology confirmed a poorly granulated MCT with characteristics suggestive of epitheliotropism, an uncommon finding with MCT. These represent the first reported cases of presumptive primary pulmonary MCT in dogs.

Mastocytome primaire pulmonaire présumé chez deux chiens. Deux chiens ont été présentés avec une volumineuse masse pulmonaire dont l'analyse cytopathologique confirma le diagnostic de mastocytome (MCT). L'un des chiens a été euthanasié suite au diagnostic. Un CT scan thoracique et une thoracotomie exploratrice du second chien ont révélé une masse pulmonaire droite nécessitant une résection pulmonaire radicale; le chien fut euthanasié. L'histopathologie a confirmé un MCT peu granulé avec des caractéristiques suggestives d'épithéliotropisme, une trouvaille inhabituelle lors de MCT. Il s'agit des premiers cas rapportés de MCT pulmonaires primaires présumés chez le chien.(Traduit par les auteurs).

Cytologic Criteria for Mast Cell Tumor Grading in Dogs With Evaluation of Clinical Outcome.

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.

Update on Mastocytosis (Part 2): Categories, Prognosis, and Treatment.

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in different organs. The organ most often affected is the skin. The World Health Organization classifies cutaneous mastocytosis into mastocytoma, maculopapular cutaneous mastocytosis, and diffuse mastocytosis. The systemic variants in this classification are as follows: indolent systemic mastocytosis (SM), aggressive SM, SM with an associated clonal hematological non-mast cell lineage disease, mast cell leukemia, mast cell sarcoma, and extracutaneous mastocytoma. The two latest systemic variants are rare. Although the course of disease is unpredictable in children, lesions generally resolve by early adulthood. In adults, however, the disease tends to persist. The goal of treatment should be to control clinical manifestations caused by the release of mast cell mediators and, in more aggressive forms of the disease, to reduce mast cell burden.

Α case of multiple bilateral testicular capsule mast cell tumours in a dog.

A 5-year-old intact male German Shepherd dog was referred with a diagnosis of leishmaniasis. Several testicular masses were palpated during the physical examination, while the diagnostic screening yielded no remarkable findings. Fine needle aspiration cytology of the masses revealed the presence of intermediately differentiated mast cell tumours. Scrotal ablation and orchiectomy were performed as a definitive treatment option. The pathological examination of the surgical specimens confirmed the diagnosis of grade II mast cell tumours and showed that they were all confined to the testicular capsule. At 7 months post-admission, the dog exhibited neither postsurgical complications nor metastatic foci and was, therefore, given a favourable prognosis. Despite their exceptionally rare occurrence, mast cell tumours should be considered for the differential diagnosis of testicular tumours.

The use of COLD-PCR, DHPLC and GeneScanning for the highly sensitive detection of c-KIT somatic mutations in canine mast cell tumours.

The conventional polymerase chain reaction (PCR)/sequencing methods may be poorly suited for the detection of somatic mutations in canine mast cell tumour (MCT) samples owing to limited sensitivity. This study was aimed at establishing novel and more sensitive methods, assessing their limit of detection and comparing their sensitivity with conventional methods.Two different 'driver' somatic mutations of c-KIT, together with the wild-type counterparts, were cloned in plasmids to prepare standard samples with known concentrations of mutated alleles in a background of wild-type alleles; the plasmids standards were assayed using either conventional or novel, highly sensitive technique. Conventional PCR/sequencing showed a sensitivity of 50-20%. Conversely, all the novel methods obtained higher sensitivities allowed reaching as low as 2.5-1.2% of the mutated DNA.The study demonstrates that early conventional methods could likely have underestimated the prevalence of KIT mutations of MCTs, therefore affecting the assessment of their relevance in prognosis and tyrosine kinase inhibitor (TKI) treatment effectiveness.

Pediatric mast cell sarcoma of temporal bone with novel L799F (2395 C>T) KIT mutation, mimicking histiocytic neoplasm.

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 tumors in cats: clinical update and possible new treatment avenues.

PRACTICAL RELEVANCE: Feline mast cell tumors (MCTs) are frequently encountered in general practice. MCTs are the most common splenic tumor, second most common skin tumor and third most common intestinal tumor in cats. Treatment and prognosis can vary dramatically with location and histologic classification. CLINICAL CHALLENGES: While a cytologic or histologic diagnosis is often easy to obtain, the various histologic classifications, lack of a relevant grading scheme, and disparity in behavior depending on anatomic location make prognostication for cases of feline MCTs confusing. This is quite different from canine MCTs, where there is an established grading system which correlates clinically with prognosis and an accepted standard of care. AUDIENCE: Due to its prevalence, general practitioners encounter MCTs regularly. In many instances, referral for diagnosis and treatment is not necessary. EVIDENCE BASE: Historically, there has been limited clinical evidence upon which to determine optimal treatment of MCTs in cats. Most recommendations are based on limited case reports or retrospective studies. With the recent introduction of receptor tyrosine kinase inhibitors to the veterinary market, there has been new research on the use of these drugs in cats, and new treatment options are on the horizon.

Mast cell sarcoma in an infant: a case report and review of the literature.

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.

Mast cell sarcoma of the scalp: the first sign of undisclosed systemic mastocytosis?

Mastocytosis is a neoplastic disease of mast cells and their CD34+ precursors, including a heterogeneous group of disorders. It is characterized by abnormal growth and accumulation of mast cells in one or more organ systems. Mast cell sarcoma is an extremely rare and aggressive disease characterized by local proliferation of atypical mast cells, destructive growth and poor prognosis, without systemic involvement. Very few clinical cases describing this entity have been reported in the literature. In this paper, we report a case of a mast cell sarcoma, localized in the scalp of a 63-year-old woman; it appears to be the first manifestation of undisclosed systemic mastocytosis.