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1.
Immunohistochemical and histochemical stains are useful adjunct techniques in the diagnosis of canine cutaneous round cell tumors, which can appear histologically similar. We applied a panel of monoclonal antibodies (recognizing tryptase, chymase, serotonin for mast cells; CD1a, CD18, MHC class II for histiocytes; CD3 for T lymphocytes; CD79a for B lymphocytes and plasma cells) and one histochemical stain (naphthol AS-D chloroacetate for chymase activity) to formalin-fixed, paraffin-embedded sections of canine cutaneous mast cell tumors, histiocytomas, lymphosarcomas, plasmacytomas, and unidentified round cell tumors. Of 21 tumors with a histologic diagnosis of mast cell tumor, 7/7 (100%) grade I, 6/7 (85.7%) grade II, and 3/7 (42.9%) grade III tumors were diagnosed as mast cell tumors based on positive staining for tryptase antigen and chymase activity. Mast cells were positive for both tryptase antigen and chymase activity, indicating equal efficacy of tryptase immunohistochemistry and chymase histochemistry. Chymase was detected immunohistochemically in both tumor and nontumor cells, while serotonin was not detected in most mast cell tumors, and thus, neither was useful in the diagnosis of mast cell tumors. Immunohistochemistry to detect CD18 and MHC class II was equally effective in staining histiocytomas, although lymphosarcoma must be ruled out through the use of CD3 and CD79a immunohistochemistry. Immunohistochemistry using three different monoclonal antibodies to human CD1a showed no cross-reactivity in canine histiocytomas and was not useful. A final diagnosis was obtained for 4/5 (80%) of the unidentified tumors, indicating the usefulness of multiple stains in poorly differentiated round cell tumors.  相似文献   

2.
Sixty-four canine cutaneous round cell tumors were divided into 25 mast cell tumors, 15 histiocytomas, nine cutaneous lymphosarcomas and 15 transmissible venereal tumors. The final diagnosis was made from cytologic, clinical and histologic findings. Cytologic features were significantly distinctive in mast cell tumor, transmissible venereal tumor, and most cases of histiocytoma and lymphosarcoma to allow a diagnostic opinion. This opinion was supported by subsequent histologic examination. In some instances cytology was considered essential in rendering a diagnostic opinion even though histology was available.  相似文献   

3.
The objective of this study was to evaluate by immunohistochemical means the nuclear expression of p27 and p21 proteins in cutaneous mast cell tumors and histiocytomas of dogs. In mast cell tumors, nine of the 13 grade I tumors, 13 of the 19 grade II tumors, and 10 of the 15 grade III tumors showed no detectable or mild p27 immunoreactivity. In contrast, one of the 13 grade I tumors, 12 of the 19 grade II tumors, and 11 of the 15 grade III tumors showed moderate or marked p21 immunoreactivity. Nineteen of the 28 histiocytomas showed no detectable or mild p27 immunoreactivity, and 24 cases showed moderate or marked p21 immunoreactivity. These findings indicate that a loss or absence of p27 expression is an early pathogenic event in mast cell and histiocyte tumorigenesis and that p21 expression may be a marker of mast cell tumor progression and histiocytoma cell proliferation.  相似文献   

4.
Multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4) is involved in lymphoid cell differentiation, particularly in the production of plasma cells. We examined the immunoreactivity of mouse monoclonal antibody Mum-1p to MUM1/IRF4 and compared it with expression of CD79a and CD20 in 109 plasmacytomas in 107 dogs. Tissues had been fixed in formalin and embedded in paraffin. One hundred one of 109 (93.5%) tumors were positive for MUM1/IRF4. The staining was nuclear with weak cytoplasmic reaction. Fifty-nine of 105 (56.2%) plasmacytomas were positive for CD79a; only 21 of 108 (19.4%) cases were positive for CD20. MUM1/IRF4 staining was performed on 139 other tumors including B- and T-cell lymphomas, histiocytic proliferations, mast cell tumors, and melanocytic tumors. The only MUM1/IRF4-positive nonplasmacytic tumors were 10 B-cell lymphomas and 1 anaplastic lymphoma. We conclude the following: 1) Antibody Mum-1p is very specific for canine plasmacytomas, 2) antibody Mum-1p is superior in sensitivity and specificity to CD79a and CD20 for the identification of canine plasmacytomas in formalin-fixed, paraffin-embedded tissues, 3) canine lymphomas that express MUM1/IRF4 are few and usually of B-cell origin, 4) other canine leukocytic and melanocytic tumors do not express MUM1/IRF4, and 5) prospective studies are needed to determine whether the expression of MUM1/IRF4, particularly in lymphomas, has prognostic significance.  相似文献   

5.
Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.  相似文献   

6.
Sixty-five canine skin neoplasms studied using immunocytochemistry, included 22 histiocytomas, 18 amelanotic melanomas, 14 cutaneous lymphosarcomas, six mast cell tumors, and five transmissible venereal tumors. Formalin-fixed, paraffin-embedded sections were stained using the avidin-biotin-peroxidase complex (ABC) immunoperoxidase technique for reactivity with S-100 protein, kappa and lambda immunoglobulin light chains, alpha-1-antitrypsin, alpha-1-antichymotrypsin, leukocyte common antigen (LCA), neuron-specific enolase, keratin, cytokeratin, muramidase, and vimentin. Detection of S-100, kappa and lambda light chains, neuron-specific enolase, and vimentin were most useful for screening these neoplasms. None of the markers examined was consistent in staining histiocytomas. While reactivity of S-100 (ten cases) and neuron-specific enolase (ten cases) was detected in some amelanotic melanomas, lambda light chain immunoglobulin (eight cases) was relatively consistent in cutaneous lymphomas. Mast cell neoplasms reacted with avidin and, therefore, were positive, even on negative control sections. Vimentin reacted strongly on all amelanotic melanomas and transmissible venereal tumors examined. These antibodies are helpful adjuncts in the differential diagnosis of canine skin tumors.  相似文献   

7.
Protein gene product 9.5 (PGP 9.5), a ubiquitin COOH-terminal hydrolase initially considered specific for neural and neuroendocrine tissues, is expressed in a variety of epithelial and mesenchymal tumors. During immunohistochemical evaluation of a cutaneous epitheliotropic T-cell lymphoma (mycosis fungoides [MF]) in a dog, strong reactivity for PGP 9.5 was observed. This unexpected result prompted us to examine PGP 9.5 immunoreactivity in 13 additional cases of canine mycosis fungoides. All tumors were confirmed as T-cell epitheliotropic lymphoma by histopathology and immunohistochemistry for CD3. Eight of 14 cases were positive for PGP 9.5, with reactivity mainly in the cytoplasm and less commonly in the nucleus. One case had strong reactivity in the cell membrane, sometimes with concurrent paranuclear staining. Immunoreactivity did not correlate with location (epidermal, dermal, and adnexal) of tumor cells. Disease outcome did not vary between PGP 9.5-positive and negative tumors. Although PGP 9.5 immunoreactivity in MF did not predict tumor behavior in these dogs, it has had prognostic value in certain human carcinomas. This unexpected staining of lymphocytes in mycosis fungoides with an antibody to PGP 9.5 demonstrates its presence in nonneuroendocrine tumors and precludes its use as the sole diagnostic marker in discrete cell tumors in the skin.  相似文献   

8.
Forty-nine cutaneous plasmacytomas in 46 dogs were studied. Tumors occurred at solitary sites in middle-aged to old dogs (mean age, 9.7 years) and most commonly involved the skin of the digits, lips, and ears. Initial diagnosis was made on the basis of light microscopic morphologic findings. Tumors were graded according to the extent of cellular differentiation and immunoreactivity to a panel of immunohistochemical markers (cytokeratins, canine IgG F[ab]2, neurofilament, neuron-specific enolase, S-100 protein, and vimentin). Immunoreactivity was limited to antibodies directed at canine IgG F(ab)2 and vimentin. Vimentin immunoreactivity was usually greater than that of canine IgG F(ab)2, but there was no correlation between immunoreactivity and histologic grade of the tumors. Thirty-six of 39 dogs (92.3%) followed (mean follow-up, 13 months) were cured by surgical excision. The results of this study indicate that canine cutaneous plasmacytomas are benign neoplasms that should be included in the differential diagnosis of cutaneous round cell tumors in dogs.  相似文献   

9.
Although synovial cell sarcoma is reported to be the most common neoplasm of the canine synovium, this retrospective study of 35 canine synovial tumors found that the majority were of histiocytic origin. Five (14.3%) synovial cell sarcomas were identified by positive immunohistochemical staining with antibodies to cytokeratin. Eighteen (51.4%) histiocytic sarcomas were identified by cell morphology and immunohistochemical staining with antibodies to CD18. Six (17.1%) synovial myxomas were identified by histologic pattern. The remaining six (17.1%) synovial tumors represented a variety of sarcomas, including two malignant fibrous histiocytomas (actin positive), one fibrosarcoma, one chondrosarcoma, and two undifferentiated sarcomas. Rottweilers were overrepresented in the histiocytic sarcoma category and Doberman Pinschers were overrepresented in the synovial myxoma category. The average survival time was 31.8 months for dogs with synovial cell sarcoma, 5.3 months for dogs with histiocytic sarcoma, 30.7 months for dogs with synovial myxoma, and 3.5 months for dogs with other sarcomas. Among the dogs with follow-up information available, metastatic disease was detected in 25% of dogs with synovial cell sarcoma, in 91% of dogs with histiocytic sarcoma, in none of the dogs with synovial myxoma, and in 100% of dogs with other sarcomas. Immunohistochemical staining for cytokeratin, CD18, and smooth muscle actin is recommended to make the diagnosis and thereby predict the behavior of synovial tumors in dogs.  相似文献   

10.
Extramedullary plasmacytomas were studied in 29 dogs. The site at which tumors occurred and the age and sex of the dogs were similar to those in previous reports. The skin of the digits, chin, ear, and lip represented the most common (17/29) tumor sites. Males and females were equally represented, and tumors occurred in middle-aged to old dogs (mean age, 9.0 years). A breed predilection was seen in the Cocker Spaniel (n = 7; 24%); Cocker Spaniels represented only 4% (210/4,725) of the submissions during the same period. Tumors were stained with immunohistochemical markers (lambda light chain, K light chain) and thioflavine T. Immunoreactivity was limited to either lambda or K light chains, consistent with a monoclonal plasma cell population. The majority of tumors expressed lambda light chains, consistent with previously reported canine plasma cell dyscrasias. Thioflavine T cytoplasmic fluorescence was seen in the majority (18/29) of plasmacytomas and with inflammatory plasma cells present in control specimens. Other round cell neoplasms (lymphosarcoma, histiocytoma, and mastocytoma) were negative with thioflavine T, indicating that positive staining with thioflavine T was specific for plasma cells (neoplastic and inflammatory). This study confirms by immunohistochemistry that canine extramedullary plasmacytomas disproportionately express lambda light chains and establishes thioflavine T staining as a rapid histochemical method for diagnosis of these tumors.  相似文献   

11.
Objective : To assess whether wounds from incomplete mast cell tumour excisions are at greater risk of healing complications than wounds from complete excisions, or cutaneous histiocytomas. Methods : Mast cell tumours and cutaneous histiocytomas submitted to Nationwide Laboratories between November 1, 2007 and April 30, 2008 were selected. Questionnaires were sent to submitting veterinarians requesting details of tumour characteristics, clinical approach to the tumour and wound healing. Results : Three hundred and eighty‐six mast cell tumours and 524 cutaneous histiocytomas were identified. One hundred and eighty‐five mast cell tumours and 244 cutaneous histiocytomas questionnaires were returned (47% response). Wound complications arose in 20% of mast cell tumours and 21% of cutaneous histiocytomas. Multivariable analysis confirmed that larger tumours, tumours on the feet and a soft/“baggy” appearance, were significantly associated with a greater frequency of problems, leading to delayed wound healing and dehiscence. Clinical Significance : Incomplete mast cell tumour excision does not lead to greater risk of wound complications. Mast cell tumour surgical wounds have a similar rate of wound complications as cutaneous histiocytoma wounds.  相似文献   

12.
Canine cutaneous histiocytoma is a common skin tumour of Langerhans cell origin. Langerhans cells are members of the dendritic cell family of antigen-presenting cells and are located in the epidermis. They are unique among the dendritic cell lineage in that they express high levels of the adhesion molecule E-cadherin. The expression of E-cadherin by the neoplastic Langerhans cells in 37 dogs with cutaneous histiocytoma was studied by flow cytometry and immunohistochemistry. In all the cases, these cells expressed E-cadherin, whereas the infiltrating lymphocytes did not.  相似文献   

13.
In this study we undertook a comprehensive analysis of a Pet Tumour Registry of the Canary Archipelago (PTR-CA) in Spain to investigate the epidemiology of canine cutaneous round cell tumours. From a database of 2526 tumours collected from 2003 to 2020, we conducted a longitudinal analysis of the main trends in diagnosis, age, multiplicity and anatomical distribution as well as a case–control study comparing these cases with the contemporaneous canine population of the Canary Archipelago to analyse breed distribution. In line with former studies, we found histiocytomas mostly affect young dogs (2, IQR 1–5) and mast cell tumours affect middle-to-old dogs (8, IQR 6–10) with grade 1 affecting at younger ages (6.5, IQR 6–8) than both grade 2 (8, IQR 6–10 years) and grade 3 (9, IQR 7–11). Histiocytomas and plasmacytomas showed a similar anatomical distribution appearing mainly on the face, head and neck regions while mast cell tumours occur mainly on limbs and trunk. Higher risk for mast cell tumours and histiocytomas were found for Bulldog-related breeds such as Boxer (ORMCT = 23.61, CI95%: 19.12–29.15, ORHCT = 10.17, CI95%: 6.60–15.67), Boston Terrier (ORMCT 19.47, CI95%: 7.73–49.05, ORHCT 32.61, CI95%: 11.81–90.07) and Pug (ORMCT 8.10, CI95%: 5.92–11.07, ORHCT 7.87, CI95%: 4.66–13.28) while Chihuahua dogs showed significantly less risk (ORMCT 0.18, CI95%: 0.09–0.33, ORHCT 0.41, CI95%: 0.21–0.78). Notably, the Canarian Mastiff, a local breed, had a low risk of suffering from a mast cell tumour which raises the question of whether this relates to a genetic peculiarity of this breed or some husbandry and environmental factor.  相似文献   

14.
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15.
Cell proliferation and apoptosis in canine cutaneous histiocytomas and transmissible venereal tumours were examined in twenty cases. The Ki-67 immunohistochemistry and Tunel methods were used to detect mitotic activity and apoptosis, respectively. The number of Ki-67 immunoreactive cells was 11.65 (+/- 1.1706) in canine cutaneous histiocytomas and 17 (+/- 2.1751) in transmissible venereal tumours. The mean values of apoptotic cells for canine cutaneous histiocytomas and transmissible venereal tumours were 13.25 (+/- 1.8758) and 8.52 (+/- 1.1007), respectively. It was considered that mitotic activity and apoptotic indices were useful in differentiation of canine cutaneous histiocytomas and transmissible venereal tumours. The correlation values for canine cutaneous histiocytomas and transmissible venereal tumours were 0.359 (+/- 0.330) and -0.232 (+/- 0.344), respectively. No significant (P > 0.05) correlation was found between mitosis and apoptosis in these two tumour types.  相似文献   

16.
Fifty-four canine cutaneous mast cell tumors were evaluated immunohistochemically for the expression of P-glycoprotein (PGP) and multidrug-resistance-associated protein (MRP). All tumors examined were graded according to the histological malignancy. ranging from grade I to III. The expression of PGP was confirmed in 15% (8/54) of whole, 33% (5/15) of grade I, 10% (3/31) of grade II, and 0% (0/8) of grade III tumors. The expression of MRP was found in 18% (10/54) of whole, 26% (4/15) of grade I, 19% (6/31) of grade II, and 0% (0/8) of grade III tumors. The cases positive to at least one of these 2 multidrug markers were 26%, 47%, 23% and 0% of whole and grade I to III tumors, respectively. These results indicate that at least 26% of canine cutaneous mast cell tumors express PGP and/or MRP and that these tumors may be resistant to several anti-cancer drugs.  相似文献   

17.
Introduction:  Aberrant expression of the proto‐oncogene c‐Met has been noted in a variety of human cancers. In dogs, inappropriate Met expression has been identified in canine osteosarcoma (OSA) tumor samples. To better define the potential role of Met dysregulation in canine cancer, we cloned canine Met, HGF, and HGF activator and evaluated their expression patterns in a variety of canine tumor cell lines.
Methods:  Canine Met, HGF, and HGF activator were cloned from normal canine liver and canine OSA cell lines using primers based on regions of homology between mouse and human sequences as well as 5' and 3' RACE.
Results:  Inappropriate expression of Met was found in canine cell lines derived from OSAs, mast cell tumors, histiocytic sarcomas, hemangiosarcoma, and melanomas. Both HGF and HGF activator were found to be expressed in several of these tumor cell lines, providing evidence of a possible autocrine loop of Met stimulation. Incubation of canine tumor cell lines with rhHGF resulted in Met autophosphorylation and activation of the downstream signaling elements Gab1, Akt and Erk1/2. Scattering of tumor cells in response to HGF occurred under conditions of cell stress, such as serum starvation. Lastly, the Met inhibitor PHA‐665752 blocked HGF induced phosphorylation of canine Met and Gab1.
Conclusions:  These studies provide evidence that similar to the case in human tumors, aberrant Met expression may play an important role in the biology of canine cancer. As such, inhibition of Met function may represent a potentially useful novel therapeutic approach.  相似文献   

18.
Eighty-three canine cutaneous mast cell tumors were graded histologically and evaluated immunohistochemically for p53 tumor-suppressor protein expression. An avidin-biotin immunohistochemical protocol incorporated a rabbit polyclonal antibody (CM-1) directed against normal and mutant p53 protein. Positive staining was observed in 44.6% (37/83) of tumors and included 50% (12/24) of grade I (well differentiated) tumors, 46.9% (23/49) of grade II (intermediate differentiation) tumors, and 20% (2/10) of grade III (poorly differentiated) tumors. A statistically significantly higher proportion (P < 0.019) of tumors from the head and neck (83.3%, 10/12), stained positive for p53 than tumors from the thorax, back, abdomen, and axilla (39.4%, 13/33), legs (35.7%, 10/28), or prepuce, scrotal, or inguinal areas (44.4%, 4/9). No statistically significant difference between p53 labeling and histologic grade, breed, or tumor size was present. Survival data were available for 53/83 (63.9%) of dogs. Positive reactivity for p53 was observed in 47% (25/53) of tumors within this group, with 57.9% (11/19) of grade I, 43.3% (13/30) of grade II, and 25% (1/4) of grade III tumors labeled. Mean survival time for the 53 dogs was 12.1 months. The median survival time for dogs with grade III tumors or tumors >5 cm was statistically significantly shorter (P < 0.0001) than for dogs with grades I and II or smaller tumors. Although p53 protein abnormalities may play a role in tumor development or behavior in some canine cutaneous mast cell tumors, immunoreactivity was not associated with lack of tumor differentiation, tumor locations previously shown to demonstrate aggressive biological behavior, breed predisposition, or survival times.  相似文献   

19.
Background –  Cutaneous T‐cell lymphoma (CTCL) in dogs is a heterogeneous disease complex, which consists of nonepitheliotropic (NE) and epitheliotropic forms. These lymphomas are readily recognized by the presence of dominant populations of cytologically atypical lymphocytes. Objective –  The objective of this study was to introduce the key features of inflamed NE‐CTCL, which is easily confused with reactive, inflammatory histiocytic disease. Animals –  Twenty‐four dogs (mean age 7.5 years) presented with inflamed NE‐CTCL. Lesions presented as nodules, plaques or masses. An initial diagnosis of cutaneous reactive histiocytosis (11 dogs) or histiocytic neoplasia (three dogs) was made by primary pathologists. Methods –  Lesions were assessed by histology and immunohistochemistry to detect canine leukocyte antigens. Lesional genomic DNA was extracted and gene rearrangement analysis of the T‐cell receptor γ locus was assessed. Results –  The cutaneous lesions consisted of pleocellular infiltration of the dermis with variable extension into the subcutis. The lesions often surrounded vessels and adnexae. Epitheliotropism was minimal or lacking. Small lymphocytes, plasma cells and intermediate to large, cytologically atypical lymphocytes were scattered between prominent histiocytic infiltrates. Atypical lymphocytes often had marked variation in the intensity of CD3 expression. Molecular clonality analysis of the T‐cell receptor γ locus revealed clonal expansion of T cells in 22 of 23 dogs tested. Conclusion –  The recognition of inflamed NE‐CTCL and its differentiation from cutaneous reactive histiocytosis depends on careful assessment of lymphocyte morphology and immunostaining patterns. Confirmation of the diagnosis is best accomplished by T‐cell antigen receptor gene rearrangement analysis.  相似文献   

20.
Presence of matrix metalloproteinases has been associated with tumor invasion and metastasis in human neoplasia. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 was determined in canine mast cell tumor tissue and normal stromal tissue from 24 dogs with spontaneously occurring cutaneous mast cell tumors. Seventeen of the mast cell tumors were of histologic grade 2, and 7 were of histologic grade 3. Gelatin zymography and computer assisted densitometry image analysis were used to quantify matrix metalloproteinase concentration. Bands from canine tissues migrated in the same location as human proenzyme and active enzyme matrix metalloproteinase 2 and matrix metalloproteinase 9 standards. A semiquantitative value for each patient sample was obtained by comparing the optical assessment density of each unknown band to the optical density of the human standard. The presence of matrix metalloproteinase 2 and matrix metalloproteinase 9 in histologic grade 2 mast cell tumors and histologic grade 3 mast cell tumors was compared, as was presence of matrix metalloproteinases in tumor and stromal tissue. There was dramatically more proenzyme matrix metalloproteinase 9 activity in histologic grade 3 mast cell tumors when compared to grade 2 tumors (P = .03). There was also dramatically more active enzyme matrix metalloproteinase 2 and active enzyme matrix metalloproteinase 9 activity in tumor tissue compared to stromal tissue (P = .02, P < .0001). This study demonstrates that the proenzyme and active enzyme forms of matrix metalloproteinase 2 and matrix metalloproteinase 9 are present in canine mast cell tumors. This appears to be related to the degree of histologic malignancy, although histologic grade 1 tumors were not evaluated.  相似文献   

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