Anti-Ri paraneoplastic neurological syndrome presenting with bilateral cranial nerve VI palsy and jaw dystonia-a distinctive syndrome within the anti-Ri spectrum? : Case report and literature review.

OBJECTIVE: Paraneoplastic neurological syndromes (PNS) are rare disorders associated with various onconeuronal antibodies. Anti-Ri antibodies (ANNA-2) are typically found in patients with opsoclonus myoclonus syndrome (OMS) and ataxia. CASE REPORT: We present an anti-Ri antibody-positive 77-year-old woman with subacute progressive bilateral cranial nerve VI palsy, gait disturbance and jaw dystonia. MRI of the brain showed hyperintense signals on T2 bitemporal without contrast enhancement. Cerebrospinal fluid (CSF) examination exhibited mild pleocytosis of 13 cells/µl and positive oligoclonal bands. CSF was overall inconspicuous for a malignant or inflammatory etiology. Immunofluorescence analysis revealed anti-Ri antibodies in both serum and CSF. Subsequent diagnostic work up resulted in a newly diagnosed ductal carcinoma of the right breast. PNS in this case partially responded to the anti-tumor therapy. CONCLUSION: This case shows similarities with recently published anti-Ri syndromes, which might form a distinct triad within the anti-Ri spectrum.

Improved antibody-guided surgery with a near-infrared dye on a pegylated linker for CEA-positive tumors.

Real-time intraoperative image-guided cancer surgery promises to improve oncologic outcomes. Tumor-specific antibodies conjugated with near-infrared (NIR) fluorophores have demonstrated the potential to enhance visualization of solid tumor margins and metastatic disease; however, multiple challenges remain, including improvement in probe development for clinical utility. We have developed an NIR-IR800 dye on a PEGylated linker (sidewinder) conjugated to the humanized anti-carcinoembryonic antigen (CEA) antibody (M5A) with extended in vivo serum and tumor persistence. The anti-CEA M5A-sidewinder has a high dye-to-antibody ratio (average of 7 per antibody) that allows, in an orthotopic implanted human pancreatic cancer mouse model increased tumor fluorescence, higher tumor-to-background ratio and extends the surgical scheduling window compared to current antibody dye conjugates. These preclinical results demonstrate the potential of this probe for fluorescence-guided surgery of CEA-positive gastrointestinal cancers.

Long-term outcomes of tissue-based ACTH-antibody assay-guided transsphenoidal resection of pituitary adenomas in Cushing disease.

OBJECTIVE Cushing disease is caused by a pituitary micro- or macroadenoma that hypersecretes adrenocorticotropic hormone (ACTH), resulting in hypercortisolemia. For decades, transsphenoidal resection (TSR) has been an efficacious treatment but with certain limitations, namely precise tumor localization and complete excision. The authors evaluated the novel use of a double-antibody sandwich assay for the real-time quantitation of ACTH in resected pituitary specimens with the goals of augmenting pathological diagnosis and ultimately improving long-term patient outcome. METHODS This study involved a retrospective review of records and an analysis of assay values, pathology slides, and MRI studies of patients with Cushing disease who had undergone TSR in the period from 2009 to 2014 and had at least 1 year of follow-up in coordination with an endocrinologist. In the operating room, biopsy specimens from the patients had been analyzed for tissue ACTH concentration. Additional samples were simultaneously sent for frozen-section pathological analysis. The ACTH assay performance was compared against pathology assessments of surgical tumor samples using receiver operating characteristic (ROC) analysis and against pre- and postoperative MRI studies. RESULTS Fourteen patients underwent TSR with guidance by ACTH-antibody assay and pathological assessment of 127 biopsy samples and were followed up for an average of 3 years. The ACTH threshold for discriminating adenomatous from normal tissue was 290,000 pg/mg of tissue, based on jointly maximized sensitivity (95.0%) and specificity (71.3%). Lateralization discordance between preoperative MRI studies and surgical visualization was noted in 3 patients, confirming the impression that MRI alone may not achieve optimal localization. A majority of the patients (85.7%) attained long-term disease remission based on urinary free cortisol levels, plasma cortisol levels, and long-term corticosteroid therapy. Comparisons of patient-months of remission and treatment failure showed that the remission rate in the study sample statistically exceeds the rate in historical controls (71.9%; p = 0.0007, Fisher's exact test). Long-term unexpected hormonal deficiencies were statistically similar between study patients (29%) and those in a meta-analysis (25%; p = 0.7596, Fisher's exact test). CONCLUSIONS These preliminary findings reflect the promising potential of tissue-based ACTH-antibody-guided assay for improving the cure rates of Cushing disease patients undergoing TSR. Further studies with larger sample sizes, further refinements of assay interpretation, and longer-term follow-ups are needed.

Role of TIM-3 in ovarian cancer

Evidences have suggested that immunotherapy for ovarian cancer is effective. Immune checkpoints have emerged in the field of cancer immunotherapy. Multiple studies have shown negative regulation of TIM-3 expression on CD4+ and CD8+ T cells and other immunocytes. Overexpression of TIM-3 in innate immune cells has been found in certain types of tumor. The blockade of TIM-3 leads to sustained anti-tumor reactions. TIM-3 plays an inhibitive role for immunity in ovarian cancer. TIM-3 is involved in the development of various subtypes of ovarian cancer and thus has the potential to be a therapeutic target for treatment of ovarian cancer (AU)

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Primordial odontogenic tumor: An immunohistochemical profile.

BACKGROUND: Primordial Odontogenic Tumor (POT) is a recently described odontogenic tumor characterized by a variably cellular loose fibrous tissue with areas similar to the dental papilla, covered by cuboidal to columnar epithelium that resembles the internal epithelium of the enamel organ, surrounded at least partly by a delicate fibrous capsule. The purpose of this study was to investigate the possible histogenesis and biological behavior of this rare tumor by means of a wide immunohistochemical analysis of its epithelial and mesenchymal components. MATERIAL AND METHODS: The immunoexpression of twenty-three different antibodies were evaluated in four cases of POT. RESULTS: The epithelial cells that cover the periphery of the tumor showed immunopositivity for Cytokeratins 14 and 19, while Amelogenin, Glut-1, MOC-31, Caveolin-1. Galectin-3, PITX2, p53, Bax, Bcl-2, Survivin and PTEN were variably expressed in focal areas. The mesenchymal component of the tumor was positive for Vimentin, Syndecan-1, PITX2, Endoglin (CD105), CD 34, Cyclin D1, Bax, Bcl-2, Survivin and p53. PTEN and CD 90 showed a moderate positivity. BRAF V600E and Calretinin were negative in all samples. Cell proliferation markers (Ki-67, MCM-7) were expressed in <5% of the tumor cells. CONCLUSIONS: According to these immunohistochemical findings, we may conclude that POT is a benign odontogenic tumor in which there is both epithelial and mesenchymal activity during its histogenesis, as there is expression of certain components in particular zones in both tissues that suggests this tumor develops during the immature (primordial) stage of tooth development, leading to its inclusion within the group of benign mixed epithelial and mesenchymal odontogenic tumours in the current World Health Organization classification of these lesions.

Comparative histological and immunohistochemical study of ameloblastomas and ameloblastic carcinomas.

BACKGROUND: This study aimed to compare the histological and immunohistochemical characteristics of ameloblastomas (AM) and ameloblastic carcinomas (AC). MATERIAL AND METHODS: Fifteen cases of AM and 9 AC were submitted to hematoxilin and eosin (H&E) and immunohistochemical analysis with the following antibodies: cytokeratins 5,7,8,14 and 19, Ki-67, p53, p63 and the cellular adhesion molecules CD138 (Syndecan-1), E-cadherin and ß-catenin. The mean score of the expression of Ki-67 and p53 labelling index (LIs) were compared between the groups using the t test. A value of p<0.05 was considered to be statistically significant. RESULTS: All cases were positive for CKs 5, 14 and 19, but negative for CKs 7 and 8. CKs 5 and 19 were positive mainly in the central regions of the ameloblastic islands, while the expression in AC was variable in intensity and localization. CK14 was also variably expressed in both AM and AC. Ki-67 (P=.001) and p53 (P=.004) immunoexpression was higher in AC. All cases were positive for p63, but values were higher in AC. CD138 was mainly expressed in peripheral cells of AM, with a weak positivity in the central areas, while it was positive in most areas of ACs, except in less differentiated regions, where expression was decreased or lost. E-cadherin and ß-catenin were weakly positive in both AM and AC. CONCLUSIONS: These results shows that Ki-67, p53 and p63 expression was higher in AC as compared to AM, suggesting that these markers can be useful when considering diagnosis of malignancy, and perhaps could play a role in malignant transformation of AM. Pattern of expression of CKs 5 and 19 in AC were different to those found in AM, suggesting genetic alterations of these proteins in malignant cells. It was confirmed that CK19 is a good marker for benign odontogenic tumors, such as AM, but it is variably expressed in malignant cases.

Nanoporous Glass Integrated in Volumetric Bar-Chart Chip for Point-of-Care Diagnostics of Non-Small Cell Lung Cancer.

Point-of-care (POC) testing has the potential to enable rapid, low-cost, and large-scale screening. POC detection of a multiplexed biomarker panel can facilitate the early diagnosis of non-small cell lung cancer (NSCLC) and, thus, may allow for more timely surgical intervention for life-saving treatment. Herein, we report the nanoporous glass (NPG) integrated volumetric bar-chart chip (V-Chip) for POC detection of the three NSCLC biomarkers CEA, CYFRA 21-1, and SCCA, by the naked eye. The 3D nanostructures in the NPG membrane efficiently increase the number of binding sites for antibodies and decrease the diffusion distance between antibody and antigen, enabling the low detection limit and rapid analysis time of the NPG-V-Chip. We utilized the NPG-V-Chip to test the NSCLC biomarker panel and found that the limit of detection can reach 50 pg/mL (10-fold improvement over the original V-Chip), and the total assay time can be decreased from 4 to 0.5 h. We then detected CEA in 21 serum samples from patients with common cancers, and the on-chip results showed good correlation with the clinical results. We further assayed 10 lung cancer samples using the device and confirmed the results obtained using conventional ELISA methods. In summary, the NPG-V-Chip platform has the ability of multiplex, low detection limit, low cost, lack of need for accessory equipment, and rapid analysis time, which may render the V-Chip a useful platform for quantitative POC detection in resource-limited settings and personalized diagnostics.

[Non-small cell lung cancer. New biomarkers for diagnostics and therapy]. / Nicht-kleinzelliges Lungenkarzinom. Neue Biomarker für Diagnostik und Therapie.

Although advances in targeted therapies have recently been achieved, lung cancer remains a major health burden worldwide. It is therefore pivotal to investigate the biology of lung cancers in order to design new therapeutic strategies. To address this a multi-antibody assay has been developed for the classification of non-small cell lung cancer (NSCLC). Using this assay the pathologist is able to reliably subtype NSCLC into adenocarcinoma, squamous cell carcinoma, large cell neuroendocrine carcinoma (LCNEC) and NSCLC not otherwise specified (NOS) large cell carcinoma, as required by the new World Health Organization (WHO) classification of 2015, on a single glass slide. In our cohort this classification algorithm showed significant differences in overall survival of the therapeutically important subgroups, which reflects the accuracy of the assay. To investigate the biology of NSCLC subtypes further, several proteins involved in carbohydrate metabolism were analyzed. In a hierarchical cluster analysis it could be shown that adenocarcinoma and squamous cell carcinoma harbor different metabolic shifts and, furthermore, that two distinct groups of squamous cell carcinoma seem to exist, a hypoxia and a transporter type. These results could be verified by analysis of mRNA data obtained from the TCGA database. As a close association between tumor metabolism and anti-tumor immune response has been reported, the lymphocytic infiltrates were characterized with respect to T-cells and their location within the tumor. Besides a negative correlation of lymphocyte density and expression of lactate dehydrogenase, it could be shown that depending on the location and type a high lymphocyte density indicates a significantly better overall survival of NSCLC patients. Investigating the expression of PD-L1 in NSCLC cells, a significant correlation with lymphocyte density was detected. In conclusion, the multi-antibody assay is a new and economically attractive tool for a reliable subclassification of NSCLC. This subtyping results in a better biological stratification of NSCLC and is the basis not only for palliative treatment options but also for further investigations on NSCLC biology. It was discovered that metabolic changes during malignant transformation are different in adenocarcinoma and squamous cell carcinoma. The latter group can be further divided into a hypoxia and a transporter type. Anti-tumor immune responses are influenced by the metabolic shift in NSCLC and lymphocyte density with respect to the location within the tumor is of prognostic significance in NSCLC. Therefore, the results contribute to a better biological understanding of NSCLC and may lead to new treatment options by targeting metabolic enzymes or triggering anti-tumor responses.

Coordinate expression of cytokeratins 7 and 14, vimentin, and Bcl-2 in canine cutaneous epithelial tumors and cysts.

Forty-seven canine cutaneous epithelial tumors and cysts were examined to determine coordinate expression of cytokeratins 7 (CK7) and 14 (CK14), vimentin, and Bcl-2 using commercially available antibodies. Within non-affected normal skin adjacent to tumors or cysts, CK7 expression was observed in luminal cells in apocrine glands; CK14 expression was observed in the stratum basale, stratum spinosum, stratum granulosum, basal layer of outer root sheath, sebaceous glands, and myoepithelial cells of apocrine glands; vimentin expression was observed in dermal papilla and scattered non-epithelial cells within the epidermis; and Bcl-2 expression was observed in scattered non-epithelial cells in the epidermis and some apocrine glands. The pattern of expression of CK7 and CK14 in cases of adenocarcinoma of the apocrine gland of the anal sac (CK7+/CK14-) and hepatoid gland tumors (CK7-/CK14+) may prove useful for diagnostic purposes. Loss of expression of CK14 and vimentin, identifying myoepithelial cells, was observed in apocrine and ceruminous adenocarcinomas. Differences in patterns of expression of Bcl-2 were observed between infundibular keratinizing acanthomas compared to trichoepitheliomas.

An 8-year old boy with continuous spikes and waves during slow sleep presenting with positive onconeuronal antibodies.

OBJECTIVE: To determine the etiology of epilepsy with continuous spikes and waves during slow sleep (CSWS)/electrical status epilepticus during sleep (ESES) in an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus. MATERIAL & METHODS: A combination of clinical characterization and follow-up, video EEG and laboratory investigations. RESULTS: We report the case of an 8-year old boy with a history of neuroblastoma and opsoclonus-myoclonus, who presented with intellectual disability, pharmacotherapy-resistant epilepsy and CSWS/ESES. Although the patient's neuroblastoma had been successfully treated 8 years prior to presentation and an extensive workup did not show a tumor reoccurrence, testing for onconeuronal antibodies was positive for anti-Ma2 and anti-CV2/CRMP5 antibodies. High-dose intravenous methylprednisolone and a taper of oral methylprednisolone were given, leading to a significant clinical improvement. During the taper the patient's condition and EEG manifestations deteriorated again necessitating another cycle of steroid therapy, which lead to a stable improvement. During a 6-month follow-up no CSWS/ESES was seen on EEG and anti-Ma2 and anti-CV2/CRMP5 antibodies remained undetectable. CONCLUSION: This case suggests that onconeuronal antibodies may be involved in the pathogenesis of CSWS/ESES.

Clinical significance of perineural invasion diagnosed by immunohistochemistry with anti-S100 antibody in Stage I-III colorectal cancer.

PURPOSE: Perineural invasion (PN) diagnosed by hematoxylin-eosin (HE) staining is an important prognostic factor after curative-intent surgery in patients with colorectal cancer. However, the clinical significance of PN diagnosed by immunohistochemistry (IHC) has not been investigated. The present study assessed the clinical significance of PN diagnosed by IHC with an anti-S100 antibody in patients with colorectal cancer. METHODS: We retrospectively enrolled 184 consecutive patients with stage I-III colorectal cancer who had undergone curative-intent surgery. We analyzed the absence/presence of PN diagnosed by HE staining (HE-PN) compared to that diagnosed by IHC with the anti-S100 antibody (S100-PN). Potential prognostic factors were identified by univariate and multivariate analyses of the overall and relapse-free survival. The [Formula: see text] statistics were used to assess the inter-observer reproducibility. RESULTS: The incidence of HE-PN and S100-PN among the 184 patients was 60 patients (32.6%) and 113 patients (61.4%), respectively (P < 0.001). A multivariate Cox proportional hazards regression model analysis indicated that S100-PN was an independent prognostic factor for both the overall and relapse-free survival. The [Formula: see text] value was 0.77 for S100-PN and 0.47 for HE-PN. CONCLUSION: PN diagnosed by IHC is an important prognostic factor in patients with colorectal cancer. An inter-observer assessment showed superior judgment reproducibility for S100-PN compared with HE-PN.

A multiplex method for the detection of serum antibodies against in silico-predicted tumor antigens.

Humoral immune responses against tumor antigens are studied as indirect markers of antigen exposure and in cancer vaccine studies. An increasing number of tumor antigens potentially translated from mutant genes is identified by advances in genomic sequencing. They represent an interesting source for yet unknown immunogenic epitopes. We here describe a multiplex method using the Luminex technology allowing for the detection of antibodies against multiple in silico-predicted linear neo-antigens in large sets of sera. The approach included 32 synthetic biotinylated peptides comprising a predicted set of frameshift mutation-induced neo-antigens. The antigens were fused to a FLAG epitope to ensure monitoring antigen binding to avidin-linked microspheres in the absence of monoclonal antibodies. Analytical specificity of measured serum antibody reactivity was proven by the detection of immune responses in immunized rabbits and a colorectal cancer patient vaccinated with peptides included in the assay. The measured antibody responses were comparable to peptide ELISA, and inter-assay reproducibility of the multiplex approach was excellent (R (2) > 0.98) for 20 sera tested against all antigens. Our methodic approach represents a valuable platform to monitor antibody responses against predicted antigens. It may be used in individualized cancer vaccine studies, thereby extending the relevance beyond the model system in the presented approach.

Spectroimmunohistochemistry: a novel form of MALDI mass spectrometry imaging coupled to immunohistochemistry for tracking antibodies.

MALDI mass spectrometry imaging (MALDI-MSI) is currently used for clinical applications, such as biomarker identification, particularly for the study of solid tumors. The ability to map specific compounds that have been determined to be biomarkers and therapeutic targets is relevant for the evaluation of the efficacy of targeted therapies. This article describes a new method called Spectro-ImmunoHistoChemistry (SIHC), which combines the use of specific antibodies against markers and mass spectrometric imaging in the MS/MS mode. SIHC is based on direct primary antibody-antigen recognition, trypsin digestion of the antibody overlaying the markers of interest in the tissue section, and MALDI-MSI of the tryptic peptides generated from the antibody. This approach has both clinical and pharmacological applications. First, it can be used as a cross-validation method to monitor the presence specifically of a marker in a tissue section. Second, SIHC could potentially be used as a novel technology for tracking specific antibodies after in vivo injection for anti-cancer treatments. Additionally, SIHC could enable novel clinical applications of MSI, such as monitoring the efficacy of cytotoxic antibody treatments.

Inmunohistoquímica en dermatopatología: revisión de los anticuerpos utilizados con mayor frecuencia (parte I) / Immunohistochemistry in Dermatopathology: A Review of the Most Commonly Used Antibodies (Part I)

La dermatopatología incluye una larga lista de entidades, algunas con una histopatología muy similar. La immunohistoquímica representa una importante herramienta de ayuda en el diagnóstico, diagnóstico diferencial y pronóstico de muchas de las neoplasias cutáneas. La inmunohistoquímica es también la mejor técnica para determinar el origen de un tejido o la diferenciación de las células neoplásicas. En muchos casos la inmunohistoquímica permite un diagnóstico más preciso de los distintos procesos infiltrando la piel. Este artículo revisa el papel de la inmunohistoquímica en el estudio de la diferenciación y el comportamiento biológico de la mayoría de las neoplasias que pueden afectar a la piel. Se revisan las técnicas de inmunoperoxidasa, se discute la utilidad de los anticuerpos utilizados con mayor frecuencia y se presentan una serie de problemas diagnósticos en los que la immunohistoquímica puede resultar muy útil. En cada caso, la finalidad es llegar a un diagnóstico concreto y definitivo. En la primera parte de esta revisión se estudian los anticuerpos que exploran las distintas líneas de diferenciación de las neoplasias cutáneas (AU)

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review the immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry maybe very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the first part of this review, we examine the antibodies that determine the different cell-differentiation profiles of skin tumors (AU)

[A man with sexual disinhibition caused by paraneoplastic limbic encephalitis]. / Een man met seksuele ontremming veroorzaakt door paraneoplastische limbische encefalitis.

A 63-year-old man with symptoms of depression and sexual disinhibition was admitted to a psychiatric clinic for the elderly. Because the man's symptoms rapidly became more severe he was referred to the emergency room. There, his illness was diagnosed as paraneoplastic limbic encephalitis with positive anti-Hu antibodies; this is a paraneoplastic neurological syndrome presenting with short-term memory loss, epileptic seizures and psychiatric symptoms. For the prognosis of the illness it is essential that the syndrome is diagnosed as early as possible. Since patients sometimes present with mainly psychiatric symptoms it is important that psychiatrists are fully informed about the symptoms and are able to make an accurate diagnosis.

Neurological paraneoplastic syndromes in lung cancer patients.

Lung cancer is recognized among the most frequent causes of paraneoplastic neurological syndromes (PNS). Neurological syndromes in subjects with systemic malignancy remain a clinical and diagnostic challenge. The aim of the study was to evaluate the frequency of NPS, their clinical manifestation and association with onconeural antibodies in patients with lung cancer. Fifty patients hospitalized with the diagnosis of PNS participated in the study. Neurological evaluation consisted of the Rankin scale (mRS), the Barthel index (BI), and testing for the presence of onconeural antibodies by means of indirect immunofluorescence, as screening, and Western blotting as confirmation. The majority of lung cancer patients (64%) aged 62 ± 10 had NPS symptoms. Their neurological condition and daily living activities were reasonable: mRS (1.0; 0.0-4.0) and BI (100; 7.4-100) scores. Classical PNS were found in 30% of cases and included sensory neuropathy (16%), paraneoplastic cerebellar degeneration (12%) as the most frequent symptoms. Autoimmune reaction was observed in 42% of lung cancer patients and in 20% was represented by well-characterized onconeural antibodies. Anti-Hu antibody was identified as the most frequent. In conclusion, PNS signs in lung cancer patients have both classical and non-classical features. In the course of SCLC only well-characterized onconeural antibodies were identified. The presence of well-characterized onconeural antibodies is strongly associated with classical features of PNS.

Topical treatment of actinic keratosis with imiquimod 5% cream / Tratamento tópico de ceratose actínica com imiquimod creme 5%

The viability and the efficiency of imiquimod 5% cream in a cat which suffered from nasal actinic keratosis were evaluated. The procedures were carried out at home by the owners themselves. Six packets of the cream were used, one per week, in three consecutive daily applications, with a four-day interval (without treatment). The cytological results were negative for neoplastic cells 30 days after the end of the treatment. A clinical revision was conducted 18 months later and the animal showed no signs of recurrence. The cream proved to be safe and efficient. There are no reports regarding efficiency in animals concerning the treatment with imiquimod 5% cream and also regarding other effects related to this treatment. A case report presenting a positive response can reveal with terapeutical possibilities that it would be easily available and applicable for all professionals. In the future it would be a new alternative to avoid progressions of this kind of neoplasia which is often observed in the small animal clinic.

Avaliaram-se a viabilidade e a eficácia da utilização do imiquimod creme 5% em um gato portador de ceratose actínica nasal. As aplicações foram realizadas no domicílio, pelos proprietários, sendo utilizados seis sachês do creme, um por semana, em protocolo de três aplicações diárias consecutivas e quatro dias de descanso (sem tratamento). Após 30 dias do término do tratamento, obteve-se citologia negativa para células neoplásicas. Em revisão clínica 18 meses após o tratamento, o paciente apresentava-se sem sinais de recidiva. O protocolo mostrou-se seguro e eficaz. Em animais não há relatos sobre a eficácia da terapia com imiquimod, bem como sobre efeitos adversos decorrentes deste tratamento. A apresentação de um caso em que se observou resposta positiva pode descortinar uma nova possibilidade terapêutica, acessível a todo clínico, que poderá evitar a progressão destas neoplasias que são frequentemente observadas na clínica de pequenos animais.