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Journal of Veterinary Diagnostic... May 2022Better understanding of mast cell tumors (MCTs) in miniature pigs is needed to guide diagnosis and establish clinical significance. We characterized the gross pathology,...
Better understanding of mast cell tumors (MCTs) in miniature pigs is needed to guide diagnosis and establish clinical significance. We characterized the gross pathology, histopathology, histochemical staining, and KIT immunoreactivity of cutaneous MCTs in a retrospective descriptive study of 11 miniature pigs (). Tumors were single or multiple papules, small nodules, or plaques. In one pig, lymph nodes and internal organs were affected. Histologically, all MCTs involved the dermis, and some extended to the subcutis (4 of 11) and skeletal muscle (1 of 11). Most tumors were well-demarcated, unencapsulated, nodular or multinodular masses (8 of 11) and fewer were poorly demarcated plaques (3 of 11). Neoplastic cells were often well-differentiated with pale amphophilic-to-eosinophilic faintly granular cytoplasm, occasional binucleation, rare multinucleation, and a low mitotic count (<7 per 10 hpf; 10 of 11). Eosinophils were present in tumors in all cases. Cytoplasmic granules stained most consistently with high-pH (2.5-3) toluidine blue (9 of 10) compared to low-pH (0.5-1) toluidine blue (6 of 9) or Giemsa (7 of 10). KIT immunoreactivity patterns were strong perimembranous (4 of 8), focal perinuclear and stippled cytoplasmic (1 of 8), and diffuse cytoplasmic (3 of 8), and included 1 case that was negative for histochemical stains; hence, KIT is a promising diagnostic marker for MCTs in miniature pigs.
Topics: Animals; Mast Cells; Mastocytoma, Skin; Proto-Oncogene Proteins c-kit; Retrospective Studies; Skin Neoplasms; Swine; Swine Diseases; Swine, Miniature; Tolonium Chloride
PubMed: 35191338
DOI: 10.1177/10406387221079255 -
Journal of the European Academy of... Aug 2022Cutaneous lesions of mastocytosis (CLM) are often subtle and may require biopsy. However, dermatohistopathological criteria for CLM remain undefined.
BACKGROUND
Cutaneous lesions of mastocytosis (CLM) are often subtle and may require biopsy. However, dermatohistopathological criteria for CLM remain undefined.
OBJECTIVES
To establish criteria for CLM by validating histological and molecular parameters.
METHODS
In skin samples from Caucasian patients with CLM and controls (atopic dermatitis, chronic urticaria, pruritus, tissue from tumor safety margin excisions), mast cell (MC) numbers, size, shape, distribution, immunostainability with a large panel of markers, pigmentation and presence of KIT D816V mutation were analysed.
RESULTS
Forty-seven CLM patients (32 maculopapular cutaneous mastocytosis (MPCM), 15 mastocytomas) and 36 controls were included. Mastocytomas were easily identified by densely packed cuboidal MCs. In MPCM, skin MC density in CD117 stains was higher in CLM patients than in controls (P < 0.0001) and values correlated closely (r = 0.65, P < 0.0001) to results in tryptase stains. The optimized upper dermis cut-off number of 62 MC/mm had a sensitivity and specificity of 92% in both stainings, corresponding to approximately 12 MC/high power field (HPF). MC size was larger in MPCM than in controls (P = 0.01). Interstitial (= not perivascular or periadnexal) MCs and stronger basal pigmentation of the epidermis were indicative of MPCM (P < 0.0001 each) and clusters of >3 nucleated MC/HPF exclusively found in MCPM. Surface markers CD2, CD25 and CD30 stained T-lymphocytes, but only negligibly CLM MC. The KIT D816V mutation in formalin fixed paraffin embedded (FFPE) skin was evaluable in 87.5% of MCPM patients and had both 100% sensitivity and specificity.
CONCLUSIONS
MPCM can be predicted by major and minor criteria combined in a scoring model. Presence of D816V mutation in FFPE skin and MC density > 27/HPF are >95%-specific major criteria for MPCM. MC densities 12/HPF, interstitial MC, clusters and basal pigmentation are minor criteria.
Topics: Biomarkers; Humans; Mast Cells; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Mutation; Proto-Oncogene Proteins c-kit; Tryptases
PubMed: 35412687
DOI: 10.1111/jdv.18143 -
Clinical and Experimental Dermatology Sep 2022Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric...
BACKGROUND
Mastocytosis is characterized by the accumulation of mast cells (MCs) in the skin or other organs, and can manifest at any age. A significant number of paediatric mastocytosis cases persist after puberty. In particular, monomorphic maculopapular cutaneous mastocytosis (mMPCM) is often persistent and associated with systemic mastocytosis. However, clinical differentiation of MPCM from polymorphic (p)MPCM can be difficult.
AIM
To identify histopathological features that can help to distinguish mMPCM from other subtypes of paediatric mastocytosis.
METHODS
This was a retrospective study using skin biopsies from patients with any subtype of mastocytosis. The localization and density of the MC infiltrate, MC morphology and expression of aberrant markers were evaluated and correlated with clinical characteristics.
RESULTS
In total, 33 biopsies were available for evaluation from 26 children [(10 with mMPCM, 5 with mastocytoma, 3 with diffuse cutaneous mastocytosis (DCM), 8 with pMPCM)] and 7 adults with MPCM. The MC number was increased in all patients, but was higher in children than adults (P < 0.01). The presence of mMPCM was associated with sparing of the papillary dermis from MC infiltration, whereas MC density in the papillary dermis was highest in pMPCM and DCM (P < 0.01). The positive predictive value of the presence of a reticular MC infiltrate for mMPCM was 72.7% (95% CI 51.4-87.0), and the negative predictive value was 83.3% (95% CI 42.2-97.2). There were no relevant differences in the expression of CD2, CD25 or CD30 between the different subtypes.
CONCLUSION
Skin histopathology might enhance the phenotypical differentiation of mMPCM from other subtypes in children, thereby increasing the accuracy of one's prognosis.
Topics: Adult; Child; Humans; Mast Cells; Mastocytosis; Mastocytosis, Cutaneous; Mastocytosis, Systemic; Proto-Oncogene Proteins c-kit; Retrospective Studies; Urticaria Pigmentosa
PubMed: 35596520
DOI: 10.1111/ced.15262 -
Journal of Veterinary Internal Medicine 2024The therapeutic role and prognostic relevance of lymphadenectomy in mast cell tumor (MCT) has historically been evaluated on regional rather than sentinel lymph nodes.
BACKGROUND
The therapeutic role and prognostic relevance of lymphadenectomy in mast cell tumor (MCT) has historically been evaluated on regional rather than sentinel lymph nodes.
HYPOTHESIS/OBJECTIVES
To update information about the association of histological nodal (HN) classes with clinical outcome in dogs with MCT after tumor excision and extirpation of normal-sized sentinel nodes (SLN) guided by radiopharmaceutical.
ANIMALS
Ninety-four dogs with histologically-confirmed treatment-naïve MCT (71 cutaneous, 22 subcutaneous and 1 conjunctival MCT) were included if without: distant metastases, lymphadenomegaly, concurrent mixed cutaneous, and subcutaneous MCT.
METHODS
This was a monoistitutional cohort study. Tumors characteristics were retrieved and SLNs were classified according to Weishaar's system. Incidence of MCT-related events (local, nodal, distant relapse), de novo MCT or other tumors and death (MCT-related and non-MCT-related), were recorded. Incidence curves were compared among the HN classes.
RESULTS
Twenty-seven dogs had HN0, 19 HN1, 37 HN2, and 11 HN3 SLN. Thirteen (2 HN0, 4 HN2, and 7 HN3) received adjuvant chemotherapies. Kiupel high grade, increasing number of SLN and lymphocentrums were associated with higher HN classes. Five dogs died for MCT-related causes: 1 low-grade (HN0) and 1 subcutaneous (HN3) had a local relapse, 2 high-grade had distant relapse (HN3-HN0) and 1 dog developed disease progression from a de novo subcutaneous MCT. No nodal relapse was registered. Fourteen dogs developed de novo MCTs.
CONCLUSION/DISCUSSION
Low grade/low-risk MCT with nonpalpable and normal sized SLN have a favorable outcome independently from the HN. Result should be considered strictly related to the successful SLN detection guided pre- and intraoperative by radiopharmaceutical markers.
Topics: Animals; Dogs; Dog Diseases; Female; Male; Lymphatic Metastasis; Sentinel Lymph Node; Lymph Node Excision; Cohort Studies; Mastocytoma; Mast-Cell Sarcoma; Treatment Outcome
PubMed: 38426589
DOI: 10.1111/jvim.16997 -
Cureus Dec 2023Congenital cutaneous mastocytoma is an uncommon disorder characterized by abnormal proliferation of mast cells. It typically presents as a single, small,...
Congenital cutaneous mastocytoma is an uncommon disorder characterized by abnormal proliferation of mast cells. It typically presents as a single, small, yellowish-brown plaque, and its diagnosis is generally facilitated by distinctive clinical features, including a positive Darrier's sign. This report presents a case of an unusually large, solitary congenital mastocytoma encompassing nearly the entire circumference of the calf, observed in a newborn boy of Bangladeshi origin. Measuring 13x6 cm, the lesion formed large bullae and subsequent erosions. The perplexing clinical appearance prompted a skin biopsy, revealing monomorphic CD117 (c-KIT) positive infiltration without significant cell pleomorphism, confirming the diagnosis of cutaneous mastocytoma. The patient underwent management with potent and very potent topical steroids, oral antihistamines, and non-adhesive dressings, remaining under long-term follow-up with secondary care dermatology. In reporting this case, our objective is to augment the existing scientific literature by providing additional evidence that cutaneous mastocytomas can display a spectrum of clinical presentations, as illustrated in this case.
PubMed: 38205464
DOI: 10.7759/cureus.50306 -
Clinical Case Reports Sep 2023The diagnosis of solitary mastocytoma is usually made clinically, however, atypical presentations may obscure the diagnosis. We present a unique case of solitary...
The diagnosis of solitary mastocytoma is usually made clinically, however, atypical presentations may obscure the diagnosis. We present a unique case of solitary cutaneous mastocytoma in an 11-month-old male initially misdiagnosed as atopic dermatitis; the diagnosis was obscured due to the development of an allergic contact dermatitis most likely secondary to topical medications that were being applied to the lesion. The diagnosis of solitary cutaneous mastocytoma is made based on lesion morphology, Darier's sign, and lack of systemic involvement. Most solitary cutaneous mastocytomas resolve before puberty; symptomatic treatment and avoidance of triggers are mainstay therapy.
PubMed: 37705587
DOI: 10.1002/ccr3.7907 -
International Journal of Molecular... Feb 2022A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl--[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide)...
A new combination of Toceranib (Toc; 5-[(5Z)-(5-Fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl--[2-(pyrrolidin-1-yl)ethyl]-1H-pyrrole-3-carboxamide) with nanohydroxyapatite (nHAp) was proposed as an antineoplastic drug delivery system. Its physicochemical properties were determined as crystallinity, grain size, morphology, zeta potential and hydrodynamic diameter as well as Toceranib release. The crystalline nanorods of nHAp were synthesised by the co-precipitation method, while the amorphous Toceranib was obtained by its conversion from the crystalline form during nHAp-Toc preparation. The surface interaction between both compounds was confirmed using Fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV-Vis) and scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS). The nHAp-Toc showed a slower and prolonged release of Toceranib. The release behaviour was affected by hydrodynamic size, surface interaction and the medium used (pH). The effectiveness of the proposed platform was tested by comparing the cytotoxicity of the drug combined with nHAp against the drug itself. The compounds were tested on NI-1 mastocytoma cells using the Alamar blue colorimetric technique. The obtained results suggest that the proposed platform shows high efficiency (the calculated IC50 is 4.29 nM), while maintaining the specificity of the drug alone. Performed analyses confirmed that nanohydroxyapatite is a prospective drug carrier and, when Toceranib-loaded, may be an idea worth developing with further research into therapeutic application in the treatment of canine mast cell tumour.
Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Dog Diseases; Dogs; Drug Carriers; Drug Delivery Systems; Drug Synergism; Durapatite; Indoles; Mastocytoma; Nanoparticles; Protein Kinase Inhibitors; Pyrroles
PubMed: 35216060
DOI: 10.3390/ijms23041944 -
RSC Advances Oct 2021The complexes: [CoL](ClO) (1), [FeL](ClO) (2), [NiL](ClO) (3) and [MnLCl] (4), with L = diethyl-1,1'-(pyridine-2,6-diyl)bis(5-methyl-1-pyrazole-3-carboxylate), were...
The complexes: [CoL](ClO) (1), [FeL](ClO) (2), [NiL](ClO) (3) and [MnLCl] (4), with L = diethyl-1,1'-(pyridine-2,6-diyl)bis(5-methyl-1-pyrazole-3-carboxylate), were synthesized and fully characterized. Structural analysis revealed two distinct patterns influenced by the counter ions where L acts as a tridentate chelating ligand. The antitumor activity of L and L' (diethyl 2,2'-(pyridine-2,6-diylbis(5-methyl-1-pyrazole-3,1-diyl)) diacetate) as well as their metal complexes, was tested by the measurement of their cytostatic and cytotoxic properties towards the blood cancer mastocytoma cell line P815. We have also investigated their interactions with the antioxidant enzyme system. As a result, [MnL'Cl] (1') exhibited the strongest activity compared to reference cis-platin with no cytotoxicity towards normal cells PBMCs (Peripheral Blood Mononuclear Cells). On the other hand, the antioxidant enzyme activity showed that the efficiency of metal complex 1' against P815 tumor cells was the rise in the SOD activity and inhibition of CAT enzyme activity. This proof of concept study allows disclosure of a new class of molecules in cancer therapeutics.
PubMed: 35494785
DOI: 10.1039/d1ra05918a -
The Journal of Dermatology Jul 2020Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1...
Ultraviolet (UV)A1 phototherapy is effective for T-cell-mediated skin diseases such as atopic dermatitis and mast cell-mediated skin diseases such as mastocytoma. UVA1 phototherapy is also effective against the sclerotic lesions of systemic sclerosis and morphea. Currently, in Japan, access to UVA1 phototherapy is limited because the UVA1 phototherapy device has not yet been approved. On the basis of our experience, we report three patients with localized scleroderma who responded successfully to UVA1 phototherapy. Efficacy was assessed by histological analysis and elastography. UVA1 successfully ameliorated sclerotic lesions, including morphea, linear scleroderma and morphea lesions in a patient with limited cutaneous systemic sclerosis. No side-effects were observed during UVA1 phototherapy.
Topics: Humans; Japan; Phototherapy; Scleroderma, Localized; Skin Diseases; Treatment Outcome; Ultraviolet Therapy
PubMed: 32383187
DOI: 10.1111/1346-8138.15368 -
Journal of the American Veterinary... Jan 2022To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors...
Marginal excision of cutaneous mast cell tumors in dogs was not associated with a higher rate of complications or prolonged wound healing than marginal excision of soft tissue sarcomas.
OBJECTIVE
To compare wound healing following planned marginal excision of cutaneous mast cell tumors (MCTs) with that of soft tissue sarcomas (STSs) and to identify risk factors for wound healing complications and delay in healing.
ANIMALS
126 dogs that underwent intentional marginal excision of cutaneous MCTs (n = 77) or subcutaneous STSs (49).
PROCEDURES
Medical records of included dogs were reviewed and signalment, tumor size, tumor location, skin closure type, time to healing, reported complications, histopathological grade, and surgical margins were recorded. These variables and outcomes (complication rate and time to complete healing) were compared between dogs in the MCT and STS groups. Potential risk factors for complications and delayed healing were analyzed.
RESULTS
No significant difference between the groups was found in any of the variables. Wound healing complication rates were 29% (22/77) for the MCT group and 31% (15/49) for the STS group. The mean ± SD time to complete healing was 16.5 ± 7.5 days for the MCT group and 17.7 ± 9.3 days for the STS group. These outcomes did not differ significantly between groups. For both groups, the use of subdermal plexus flap reconstruction was associated with the development of complications and increased time to complete healing.
CLINICAL RELEVANCE
Marginal excision of cutaneous MCTs was not associated with a higher rate of complication or prolonged wound healing, compared with marginal excision of STSs. The use of flap reconstruction in skin closure may delay healing and planned adjuvant therapy. Owners should be counseled regarding these risks and where appropriate and feasible, surgery without reconstruction should be considered.
Topics: Animals; Dog Diseases; Dogs; Mast Cells; Mastocytoma, Skin; Neoplasm Recurrence, Local; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Treatment Outcome; Wound Healing
PubMed: 35092664
DOI: 10.2460/javma.21.05.0235