Recommendations for the Use of Tryptase in the Diagnosis of Anaphylaxis and Clonal Mastcell Disorders.

Summary: Tryptase is a serin-protease produced and released by mast cells after IgE-mediated or non-IgE mediated stimuli. We here review the various aspects related to the molecular characteristics of the enzyme and its biological effects, the genetic basis of its production and the release kinetics. Recommendations for the clinical use of tryptase measurement developed by a task force of Società Italiana di Patologia Clinica e Medicina di Laboratorio and Associazione Allergologi Immunologi Italiani Territoriali e Ospedalieri are given on the best procedure for a correct definition of the reference values in relation to the inter-individual variability and to the correct determination of tryptase in blood and other biological liquids, in the diagnosis of anaphylaxis (from drugs, food, insect sting, or idiophatic), death from anaphylaxis (post mortem assessment) and cutaneous or clonal mastcell disorders.

DNA purification increases PCR-amplifiable DNA extracted from formalin-fixed, paraffin-embedded canine mast cell tumors for routine KIT mutation detection.

DNA amplification by PCR detects KIT exon 11 internal tandem duplications in canine mast cell tumors (MCTs). Tissue-specific inhibitors often contaminate DNA extracted from formalin-fixed, paraffin-embedded (FFPE) canine MCTs, blocking PCR amplification and, consequently, preventing mutation detection. We used a commercial kit to extract DNA from FFPE canine MCTs. Two independent PCR assays, each with one primer set, were used to amplify target genes (HPRT and KIT) directly after FFPE DNA extraction. PCR amplification failed with at least one primer set in 153 of 280 samples (54.6%, 95% CI: 48.8-60.5%). One or 2 DNA washing steps were required to remove PCR inhibitors in 130 of 280 (46.4%) and 23 of 280 (8.2%) of these cases, respectively. DNA concentration and quality (A260/A280 and A260/A230) either pre- or post-washing were not associated with ability of the samples to be amplified by PCR using both HPRT and KIT primer sets. Low-grade and subcutaneous MCTs were less likely to amplify directly after DNA extraction and without any washing steps compared to high-grade MCTs using KIT gene primers.

Nanog Expression and Proliferation Indices in Canine Cutaneous Mast Cell Tumors.

Mast cell tumors are one of the most frequent skin tumors in dogs. Treatment decisions often depend on a wide range of clinical information and the main criteria for prognostic formulation are histological grade, mitotic count, Ki67 index, and KIT immunostaining pattern. NANOG is a pluripotency factor expressed by normal and cancer stem cells, which is a prognostic marker and a potential therapeutic target for several human tumors. In the present study, mast cell tumor samples from 41 dogs were evaluated for NANOG and Ki67 by immunohistochemistry. All samples were positive for NANOG but its expression was not correlated with Ki67 index and no significant differences were found with respect to histopathological grades, disease-related mortality, or survival. Our results suggest that, although related to pluripotency, NANOG expression does not correlate with proliferative activity, and is not a reliable prognostic factor for canine cutaneous mast cell tumors.

Mastocitoma solitario / Solitary mastocytoma

La mastocitosis consiste en una proliferación anormal de mastocitos en los tejidos, y el mastocitoma solitario es una de las formas más frecuentes. La evolución tiende a la curación espontánea, si bien un mínimo porcentaje de mastocitomas solitarios requieren extirpación quirúrgica (AU)

Mastocytosis is abnormal proliferation of tissue mast cells, being solitary mastocytoma the most common. Evolution tends to spontaneous healing, although a small percentage of solitary mastocytoma require surgical removal (AU)

Solitary mastocytoma of the eyelid.

Mastocytosis is a heterogeneous group of diseases characterized by the proliferation and abnormal infiltration of mast cells in tissue. These collections of mast cells are called mastocytomas. Solitary mastocytomas are cutaneous lesions, most commonly involving the extremities and trunk. Rubbing a cutaneous mastocytoma lesion leads to the release of histamine and other chemical mediators causing the lesion to become elevated and urticarial, similar to an allergic reaction. We describe a rare location of a presumed solitary mastocytoma of the lower eyelid in a young otherwise healthy child.

Heterogeneity of internal tandem duplications in the c-kit of dogs with multiple mast cell tumours.

Mast cell tumours are one of the most common neoplasms in dogs. Mutations in the proto-oncogene c-kit, especially internal tandem duplications of exon 11, are considered to play a crucial role in mast cell tumourigenesis. In this report, two cases that suffered from multiple mast cell tumours containing an internal tandem duplication in the primary lesion but not in the secondary lesions are described. This finding indicates the existence of heterogenous c-kit gene mutations in each site of multiple mast cell tumours. Additionally, these results raise the possibility that the contribution of internal tandem duplications in the malignant transformation of mast cells is quite limited. It is proposed that, for clinicians, genetic analysis of several regions of multiple mast cell tumours is necessary for predicting prognosis and tumour response to KIT inhibitors.

Differential diagnosis of round or discoid lesions.

Dermatologists are called on to diagnose a variety of skin conditions in diverse age groups. Dermatologic diagnosis, based on identification of a primary lesion, uses morphologic clues to categorize the pathologic process causing the eruption. In addition, distribution and grouping of lesions helps support a specific diagnosis. Dermatologists consciously or unconsciously use pattern recognition to arrive at their differential diagnosis based on clinical experience and their having previously viewed similarly appearing skin lesions in lectures, texts, and journals. Round and discoid patches and plaques are extremely common in the clinical practice of dermatology. This contribution reviews the dermatologic conditions that present as round or discoid lesions and presents an approach to diagnosis.

¹8F-FDG and ¹¹C-MET positron emission tomography findings of cutaneous mast cell tumor in a dog.

A 12-year-old intact male Maltese dog presented with an inguinal mass. Histopathology revealed a grade III mast cell tumor. Computed tomography demonstrated pulmonary and inguinal nodules and masses. Chemotherapy was performed using a vinblastine/prednisone protocol, and the inguinal mass disappeared 5 weeks later. Use of 2-deoxy-2-[¹8F]fluoro-D-glucose (¹8F-FDG) and (L)-[methyl- ¹¹C]methionine (¹¹C-MET)-positron emission tomography (PET) demonstrated hypermetabolic areas in the lungs and inguinal region one week after initial chemotherapy. The standardized uptake values of ¹8F-FDG were not different between lung and inguinal lesions; however, the inguinal lesion had a higher ¹¹C-MET standardized uptake value than the lung lesions. The hypermetabolic area was still visible on the second ¹8F-FDG-PET scan despite the disappearance of the mass. This is the first report of ¹¹C-MET-PET findings associated with a cutaneous mast cell tumor in a dog.

VEGF expression in dog mastocytoma.

UNLABELLED: The biologic behavior of mastocytomas is highly variable; some tumors have a benign behavior, whereas others exhibit aggressive growth and metastasis. Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis and a potential autocrine growth factor for neoplastic cells in various malignancies. MATERIAL AND METHOD: In the present study, we have investigated expression of VEGF in cutaneous tumor from a dog and combined immunohistochemical expression of VEGF with mast cell tryptase, CD117 and vimentin. RESULTS: Tumor cells were positive for VEGF, and inflammatory cells were negative. VEGF expression was found in tumor cells as a heterogeneous positive reaction, with cytoplasmic pattern and moderate to strong in intensity. Arrangement of tumor cells was in clusters, in deepest part, close to the proliferation front. The dog died 5 month from the diagnosis, and our observation suggest that VEGF secretion by tumor cells correlates with unfavorable prognosis.

Mastocytoma in the common carpal sheath of the digital flexor tendons of a horse.

A 13-year-old Morgan gelding was examined for right forelimb lameness and tenosynovitis of the right common carpal sheath of the digital flexor tendons. The horse had moderate right forelimb lameness at the trot and marked effusion of the right common carpal sheath of the digital flexor tendons. Ultrasonographic examination revealed a soft tissue mass within the proximal pouch of the affected tendon sheath, located adjacent to the distal physis of the radius. Cytology and culture of the fluid revealed a sterile, eosinophilic tenosynovitis. Tenoscopic exploration confirmed the presence of a capsulated soft tissue mass. Thecotomy was required to fully debride the mass, which histology revealed to be a mast cell tumour. At 22 months postoperatively, the horse developed mild right forelimb lameness and eosinophilic tenosynovitis because of recurrence of the mastocytoma. Mastocytosis is a possible differential diagnosis in any horse exhibiting lameness associated with tenosynovitis. Surgical excision combined with rest and postoperative intrasynovial and systemic corticosteroids may be palliative.

Multiple distinct malignancies in dogs: 53 cases.

Despite the clinical recognition of multiple distinct types of neoplasia in individual dogs, a detailed description of such cases has not recently been published. Canine oncology cases that were diagnosed with multiple, confirmed, distinct malignancies were prospectively collected for analysis. Approximately 3% of 1722 dogs that were presented to the oncology service at the Colorado State University Veterinary Medical Center were diagnosed with multiple distinct primary tumors. No significant breed or sex predisposition was apparent. Dogs with mast cell tumor, malignant melanoma, and thyroid carcinoma were significantly overrepresented and thus more likely to be diagnosed with multiple tumor types. These findings emphasize the importance of thorough, whole-body evaluation for dogs presented with mast cell tumor, malignant melanoma, and thyroid carcinoma. Furthermore, because approximately 33% of dogs that were presented with thyroid tumors were found to have additional distinct tumors, complete staging is justified in all dogs presented with thyroid tumors.