Mantle Cell Lymphoma Under the Scope of Personalized Medicine: Perspective and Directions.

Mantle cell lymphoma (MCL) is a rare, incurable non-Hodgkin's lymphoma characterized by naive B cells infiltrating the lymphoid follicle's mantle zone. A key feature of MCL is the cytogenetic abnormality t(11;14) (q13:q14), found in 95% of cases, leading to Cyclin D1 overexpression resulting in uncontrolled cell cycle progression and genetic instability. Occasionally, Cyclin D2 or D3 overexpression can substitute for Cyclin D1, causing similar effects. The transcription factor SOX11 is a hallmark of classical Cyclin D1-positive MCL and also in cases without the typical t(11;14) abnormality, making it an important diagnostic marker. MCL's development necessitates secondary genetic changes, including mutations in the ATM, TP53, and NOTCH1 genes, with the TP53 mutation being the only genetic biomarker with established clinical prognostic value. The Mantle Cell Lymphoma International Prognostic Index (MIPI) score, which considers age, performance status, serum LDH levels, and leukocyte count, stratifies patients into risk groups. Histologic variants of MCL, such as classic, blastoid, and pleomorphic, offer additional prognostic information. Recent research highlights new mutations potentially tied to specific populations among MCL patients, suggesting the benefit of personalized management for better predicting outcomes like progression-free survival. This approach could lead to more effective, risk-adapted treatment strategies. However, challenges remain in patient stratification and in developing new therapeutic targets for MCL. This review synthesizes current knowledge on genetic mutations in MCL and their impact on prognosis. It aims to explore the prognostic value of genetic markers related to population traits, emphasizing the importance of tailored molecular medicine in MCL.

LOPH: a novel chemotherapeutic protocol for feline high-grade multicentric or mediastinal lymphoma, developed in an area endemic for feline leukemia virus.

OBJECTIVES: The aim of this study was to establish the safety and efficacy of a novel multidrug lomustine-based chemotherapeutic protocol for cats with high-grade multicentric or mediastinal lymphoma, in an area endemic for feline leukemia virus (FeLV). METHODS: This prospective study included owned cats, diagnosed (cytologically) with multicentric or mediastinal lymphoma and treated with the LOPH (lomustine, vincristine [Oncovin; Antibióticos do Brasil], prednisolone and hydroxydaunorubicin [doxorubicin]) protocol. A complete blood count was performed before every chemotherapy session and any significant abnormalities recorded as possible related toxicities. Median survival time (MST) and disease-free interval were estimated by Kaplan-Meier curves. RESULTS: Twenty-one cats were included in this study. Nineteen (90.5%) tested positive for FeLV and were therefore considered to have persistent viremia. Complete response was reported in 81% (n = 17/21), while three had partial remission and one had no response. Seven cats finished the induction protocol within 20-31 weeks (23.1 ± 4.5; median 20) and all seven received a maintenance protocol. The MST (lymphoma-related survival) for the 21 cats was 214 days. The MST was 214 days for cats with mediastinal lymphoma (n = 13), but it was not reached for multicentric lymphoma (n = 8; P = 0.9). The MST of cats with persistent FeLV antigenemia was 171 days. Grade I anorexia and vomiting occurred in 19% of the cats (n = 4/21). Hematologic toxicity was found in 100% of the cats at some point during their treatment, but it was mostly grade I or II. Neutropenia, thrombocytopenia and anemia occurred in 16/21, 21/21 and 15/21 cats, respectively. CONCLUSIONS AND RELEVANCE: The LOPH protocol was well tolerated by cats with lymphoma and persistent FeLV viremia, and resulted in a better MST than similar studies with other protocols. Novel studies and controlled trials are necessary in order to evaluate the efficacy of different protocols according to the lymphoma subtype, anatomic form and FeLV status.

Extranodal B cell lymphoma in the trachea of a domestic cat

Background: Primary tracheal tumors are considered uncommon in veterinary medicine and among them extranodal tracheal lymphoma, which is a neoplastic type, has rarely been described, especially with the use of immunophenotyping. Consequently, there is a lack of knowledge inherent to the characteristics of this tumor type in felines and as a result little information on how to deal with animals affected by this disease. Therefore, there is a need for more studies focusing on this matter. The objective of this work is to report a case of extranodal B cell lymphoma in the trachea of a domestic cat and point out the clinical and pathological characteristics of this neoplastic type. Case: A 5-year-old domestic cat, of an oriental breed, was taken to a veterinary clinic exclusively for cats in Rio de Janeiro, Brazil. The main complaint was difficulty in breathing and loss of appetite and historical data included intolerance to exercise. A clinical examination confirmed inspiratory dyspnea and upper respiratory sounds. Hematological and serum biochemical exams did not evidence any noteworthy changes and the cat was considered negative for feline viral leukemia and feline immunodeficiency viruses through serological and molecular testing. However, in the radiographic examination of the thoracic cervical region, an opacity was observed that occluded part of the tracheal lumen and this was suggestive of a mass in the initial third of the trachea, measuring 0.5 cm in diameter. The animal was stabilized and then 24 h after admission underwent inspection of the oral cavity and a biopsy of the tracheal mass was performed. Cytology of the specimen was suggestive of lymphoma. The treatment of choice was: lomustine with a single, oral dose of 10 mg; vincristine sulfate with a single intravenous dose of 0.75 mg/m²; and methylprednisolone acetate with a single...(AU)

Extranodal B cell lymphoma in the trachea of a domestic cat

Background: Primary tracheal tumors are considered uncommon in veterinary medicine and among them extranodal tracheal lymphoma, which is a neoplastic type, has rarely been described, especially with the use of immunophenotyping. Consequently, there is a lack of knowledge inherent to the characteristics of this tumor type in felines and as a result little information on how to deal with animals affected by this disease. Therefore, there is a need for more studies focusing on this matter. The objective of this work is to report a case of extranodal B cell lymphoma in the trachea of a domestic cat and point out the clinical and pathological characteristics of this neoplastic type. Case: A 5-year-old domestic cat, of an oriental breed, was taken to a veterinary clinic exclusively for cats in Rio de Janeiro, Brazil. The main complaint was difficulty in breathing and loss of appetite and historical data included intolerance to exercise. A clinical examination confirmed inspiratory dyspnea and upper respiratory sounds. Hematological and serum biochemical exams did not evidence any noteworthy changes and the cat was considered negative for feline viral leukemia and feline immunodeficiency viruses through serological and molecular testing. However, in the radiographic examination of the thoracic cervical region, an opacity was observed that occluded part of the tracheal lumen and this was suggestive of a mass in the initial third of the trachea, measuring 0.5 cm in diameter. The animal was stabilized and then 24 h after admission underwent inspection of the oral cavity and a biopsy of the tracheal mass was performed. Cytology of the specimen was suggestive of lymphoma. The treatment of choice was: lomustine with a single, oral dose of 10 mg; vincristine sulfate with a single intravenous dose of 0.75 mg/m²; and methylprednisolone acetate with a single...

Intradural extramedullary plasmacytoma in a dog

Background: Plasmacytoma is a neoplasm originating in plasma cells, derived from B lymphocytes. Extramedullary presentation is the most common form of plasmacytoma, mainly in the skin and rarely in other tissues, including the vertebral canal. Extramedullary plasmacytoma (EMP) occurs more frequently in senile dogs and rarely in cats and some dog breeds have predisposition for this type of neoplasm. The aim of this study was to report plasmacytoma in a dog located adjacent to the thoracic vertebrae. Case: An approximately 5-year-old mongrel male with sudden paraplegia resulting from upper motor neuron injury was admitted to a University Hospital. The dog presented a six-centimeter diameter mass in the dorsal region, adjacent to the thoracic vertebrae. The leucogram presented mild leukopenia by eosinopenia and lymphopenia. Myelogram associated with epidurography showed a fill failure in the contrast column between the seventh and ninth thoracic vertebrae, and there were no osteolysis points in the thoracic vertebrae, adjacent to the neoplastic mass. The evaluation of the intervertebral spaces between the fourth to ninth thoracic vertebrae presented no increase in radiopacity, nor alterations in the size of intervertebral spaces, indicating intervertebral disc extrusion. The laterolateral radiographs showed an alignment of the vertebrae and vertebral canal, without presence of bone neoformations on the ventral face of the vertebral bodies. The animal was euthanized and fragments of mass were collected for histological analysis. Macroscopic findings presented a non-encapsulated well-delimited mass, with color ranging from white to reddish. Microscopically, there was proliferation of moderately differentiated round cells in bone and muscle tissues, arranged in mantle…(AU)

Intradural extramedullary plasmacytoma in a dog

Background: Plasmacytoma is a neoplasm originating in plasma cells, derived from B lymphocytes. Extramedullary presentation is the most common form of plasmacytoma, mainly in the skin and rarely in other tissues, including the vertebral canal. Extramedullary plasmacytoma (EMP) occurs more frequently in senile dogs and rarely in cats and some dog breeds have predisposition for this type of neoplasm. The aim of this study was to report plasmacytoma in a dog located adjacent to the thoracic vertebrae. Case: An approximately 5-year-old mongrel male with sudden paraplegia resulting from upper motor neuron injury was admitted to a University Hospital. The dog presented a six-centimeter diameter mass in the dorsal region, adjacent to the thoracic vertebrae. The leucogram presented mild leukopenia by eosinopenia and lymphopenia. Myelogram associated with epidurography showed a fill failure in the contrast column between the seventh and ninth thoracic vertebrae, and there were no osteolysis points in the thoracic vertebrae, adjacent to the neoplastic mass. The evaluation of the intervertebral spaces between the fourth to ninth thoracic vertebrae presented no increase in radiopacity, nor alterations in the size of intervertebral spaces, indicating intervertebral disc extrusion. The laterolateral radiographs showed an alignment of the vertebrae and vertebral canal, without presence of bone neoformations on the ventral face of the vertebral bodies. The animal was euthanized and fragments of mass were collected for histological analysis. Macroscopic findings presented a non-encapsulated well-delimited mass, with color ranging from white to reddish. Microscopically, there was proliferation of moderately differentiated round cells in bone and muscle tissues, arranged in mantle

Linfoma difuso de células B rico en células T en un canino: reporte de caso / Canine diffuse lymphoma of B-cell rich in T-cell: a case report / Linfoma difuso de células B rico em células T em um canino: relato de caso

Resumen Se reporta el caso de un Linfoma difuso de células grandes de células B rico en células T de bajo grado de comportamiento multicéntrico diagnosticado mediante evaluación histopatológica e inmunohistoquímica en un canino. En febrero de 2016 se remite al área de cátedra y servicio de patología veterinaria de la Universidad de Nariño, Pasto, Colombia, un canino hembra mestiza de ocho años de edad; el propietario reporta la presencia de dos masas en el cuello, decaimiento, anorexia y pérdida de peso. Se realiza biopsia por aspiración con aguja fina (BACAF) de masas submandibulares y linfonodos poplíteos evidenciando proliferación neoplásica de células redondas de característica linfoide, por lo cual el propietario decidió realizar eutanasia y necropsia. Se tomaron muestras para realizar la técnica de inclusión en parafina y coloración de Hematoxilina - Eosina (H/E) de rutina, adicionalmente se emplearon anticuerpos inmunohistoquímicos para CD45, CD3 y CD79a DAKO® los cuales se aplicaron a médula ósea, nódulos linfáticos, piel y fueron contrastados con hematoxilina de Meyer. Los hallazgos de H/E e inmunohistoquímica corresponden a un linfoma difuso de células B rico en células T de bajo grado, de comportamiento multicéntrico con metástasis en páncreas, hígado, pulmón, intestino delgado, médula ósea y piel. Se concluye que el uso de marcadores inmunohistoquímicos demuestran ser una herramienta de gran utilidad para el diagnóstico de neoplasias linfoides al correlacionarlos con la evaluación clínica e histopatológica.

Abstract Was reported a diffuse large cell lymphoma, both B cell and rich in T cell, low-grade behavior multicenter, diagnosed by histopathological and immunohistochemical evaluation. In February 2016 in the veterinary clinic "Carlos Martinez H." University of Nariño, Pasto, Colombia, entered a canine female, crossbreed, eight years old; owner reported the presence of two masses in neck, with decay, anorexia and weight loss. Was taken a sample fine-needle biopsy aspiration (FNA) of submandibular masses and popliteal lymph nodes, showing neoplastic proliferation of round cells of lymphoid feature, so the owner decided to perform euthanasia and necropsy. Were sampled for inclusion paraffin technique, and staining hematoxylin - eosin (H / E), further immunohistochemical antibodies to CD45, CD3 and CD79a DAKO® which were applied and were compared with hematoxylin-eosin finds. Findings belong to diffuse lymphoma diffuse of B-cell rich in low-grade T-cell with multicentric distribution with metastases in pancreas, liver, lung, small intestine, bone marrow and skin. In conclusion, use of immunohistochemically markers proves a useful tool for diagnosis of lymphoid neoplasms when the findings are correlated with clinical and histopathological evaluation.

Resumo O caso de um linfoma difuso de células grande de células B rico em células T baixo grau comportamento multicêntrico diagnosticada por histopatológico e imuno-histoquímica em um canino é relatado. Em fevereiro de 2016, refere-se à área de ensino e serviço de patologia veterinária da Universidade de Nariño, Pasto, Colômbia, uma fêmea mestiça canino oito anos de idade; o proprietário relatou a presença de dois massas cervicais, deterioração, anorexia e perda de peso. Biópsia aspiração é executada com aspiração com agulha fina (FNA) de massas dos nodos linfáticos submandibulares poplítea e que mostram a proliferação neoplásica de células redondas recurso linfoide, ou que o proprietário decidiu eutanásia e necropsia. Foram tomadas amostras para inclusão em parafina técnica e hematoxilina - eosina (H/E), adicionalmente foi usado os anticorpos imuno-histoquímica CD45, CD3 e CD79a - DAKO® que foram aplicadas para a medula óssea, os nódulos linfáticos, e a pele a foram comparadas com a corante hematoxilina de Meyer. Os resultados de H/E e imuno-histoquímica para corresponder a um linfoma difuso de células grande de células B rico em células T baixo grau comportamento multicêntrico com metástase no pâncreas, fígado, pulmão, intestino delgado, medula óssea e pele. Conclui-se que o uso de marcadores imuno-histoquímica se revela uma ferramenta útil para o diagnóstico de neoplasias linfoides para correlacionar com a avaliação clínica e histopatológica.

Intranasal lymphoma in dog: clinical-pathological aspects and immune histochemical / Linfoma intranasal em cão: aspectos clínicopatológicos e imunoistoquímicos

The canine lymphoma rarely involves the nasal cavity. The diagnosis can be established by means of cytology, histology and immunohistochemistry, where the latter is a valuable technique for identification and classification of tumor cells. The study describes a case of intranasal lymphoma in a dog, with the aid of immunodiagnostic. A canine, male, seven years old mongrel, had volume growth in all nasal dorsal and lateral, in association with anterior uveitis. As a complementary exam was asked to cytology of lymph nodes and nasal tumor. The cytological evaluation of the lymph nodes showed the presence of amastigotes of Leishmania spp., while the cytology of nasal tumors exhibited morphological pattern indicative of lymphoma. The animal euthanasia was opted and same animal was submitted for necropsy. The autopsy findings included the presence of tumor to the fullest extent of the nasal cavities, causing complete luminal obliteration. Nasal tumor, liver and eye fragments were collected, which were sent for histopathological analysis, and which revealed neoplastic proliferation, consisting of round cells, and suggested conducting immunohistochemical analysis to confirm the diagnosis. The immunohistochemical profile applied detected a lymphoma cells Natural Killer. The intranasal lymphoma in dogs is often overlooked in the differential diagnosis of upper respiratory tract diseases. It is fundamental to the realization of immunohistochemical test, because it amounts to a valuable diagnostic tool for patients with lymphoma

O linfoma canino raramente envolve a cavidade nasal. O diagnóstico pode ser estabelecido por meio da citologia, histopatologia e imunoistoquímica, onde a ultima é uma técnica valiosa para a identificação e classificação de células tumorais. O trabalho objetivou descrever um caso de linfoma intranasal em um canino, com o auxílio do imunodiagnóstico. Um canino, macho, sete anos de idade, sem raça definida, possuía aumento de volume em toda região nasal dorsal e lateral, em associação com uveíte anterior. Como exame complementar solicitou-se citologia de linfonodos e da tumoração nasal. A avaliação citológica dos gânglios linfáticos evidenciou a presença de formas amastigotas de Leishmania spp., enquanto a citologia da tumoração nasal exibiu padrão morfológico indicativo de linfoma. Optou-se pela eutanásia do animal e o mesmo foi encaminhado para necropsia. Os achados necroscópicos incluíram a presença de tumor em toda a extensão das cavidades nasais, ocasionando completa obliteração luminal e perda total dos ossos endoturbinados e conchas nasais. Foram coletados fragmentos do tumor nasal, fígado e globo ocular, os quais foram encaminhados para análise histopatológica, a qual revelou proliferação neoplásica, composta por células redondas, sendo sugerida a realização de análise imunoistoquímica para confirmação diagnóstica. O perfil imunoistoquímico aplicado detectou um linfoma de células Natural Killer. O linfoma intranasal em cães muitas vezes é negligenciado no diagnóstico diferencial das enfermidades do trato respiratório superior. Torna-se fundamental a realização do ensaio imunoistoquímico, pois equivale a uma valiosa ferramenta diagnóstica para os pacientes com linfoma

Intranasal lymphoma in dog: clinical-pathological aspects and immune histochemical / Linfoma intranasal em cão: aspectos clínicopatológicos e imunoistoquímicos

The canine lymphoma rarely involves the nasal cavity. The diagnosis can be established by means of cytology, histology and immunohistochemistry, where the latter is a valuable technique for identification and classification of tumor cells. The study describes a case of intranasal lymphoma in a dog, with the aid of immunodiagnostic. A canine, male, seven years old mongrel, had volume growth in all nasal dorsal and lateral, in association with anterior uveitis. As a complementary exam was asked to cytology of lymph nodes and nasal tumor. The cytological evaluation of the lymph nodes showed the presence of amastigotes of Leishmania spp., while the cytology of nasal tumors exhibited morphological pattern indicative of lymphoma. The animal euthanasia was opted and same animal was submitted for necropsy. The autopsy findings included the presence of tumor to the fullest extent of the nasal cavities, causing complete luminal obliteration. Nasal tumor, liver and eye fragments were collected, which were sent for histopathological analysis, and which revealed neoplastic proliferation, consisting of round cells, and suggested conducting immunohistochemical analysis to confirm the diagnosis. The immunohistochemical profile applied detected a lymphoma cells Natural Killer. The intranasal lymphoma in dogs is often overlooked in the differential diagnosis of upper respiratory tract diseases. It is fundamental to the realization of immunohistochemical test, because it amounts to a valuable diagnostic tool for patients with lymphoma(AU)

O linfoma canino raramente envolve a cavidade nasal. O diagnóstico pode ser estabelecido por meio da citologia, histopatologia e imunoistoquímica, onde a ultima é uma técnica valiosa para a identificação e classificação de células tumorais. O trabalho objetivou descrever um caso de linfoma intranasal em um canino, com o auxílio do imunodiagnóstico. Um canino, macho, sete anos de idade, sem raça definida, possuía aumento de volume em toda região nasal dorsal e lateral, em associação com uveíte anterior. Como exame complementar solicitou-se citologia de linfonodos e da tumoração nasal. A avaliação citológica dos gânglios linfáticos evidenciou a presença de formas amastigotas de Leishmania spp., enquanto a citologia da tumoração nasal exibiu padrão morfológico indicativo de linfoma. Optou-se pela eutanásia do animal e o mesmo foi encaminhado para necropsia. Os achados necroscópicos incluíram a presença de tumor em toda a extensão das cavidades nasais, ocasionando completa obliteração luminal e perda total dos ossos endoturbinados e conchas nasais. Foram coletados fragmentos do tumor nasal, fígado e globo ocular, os quais foram encaminhados para análise histopatológica, a qual revelou proliferação neoplásica, composta por células redondas, sendo sugerida a realização de análise imunoistoquímica para confirmação diagnóstica. O perfil imunoistoquímico aplicado detectou um linfoma de células Natural Killer. O linfoma intranasal em cães muitas vezes é negligenciado no diagnóstico diferencial das enfermidades do trato respiratório superior. Torna-se fundamental a realização do ensaio imunoistoquímico, pois equivale a uma valiosa ferramenta diagnóstica para os pacientes com linfoma(AU)