Linfoma no Hodgkin: primera y segunda neoplasia o, transformación histológica: dificultad diagnóstica: reporte de un caso / Non-Hodgkin's lymphoma: first and second neoplasia or, histological transformation: diagnostic difficulty: a case report

El LF es una enfermedad heterogénea con muchos diferentes subgrupos, en términos de edad de inicio, órganos involucrados (especialmente sitios extranodales) y anormalidades genéticas. Con grandes variaciones en el curso clínico, algunas veces muy indolente o no; puede mostrar transformación a linfomas de alto grado, se han reportado transformaciones a Linfoma de Células Grandes B Difusas (siendo este el más común), de Burkitt, Leucemia/Linfoma, Linfoma Linfoblástico (reportado en raras ocasiones), con un curso clínico agresivo. En el 2008 la OMS estableció 3 nuevas variantes: 1) LF Pediátrico, 2) LF Primario Intestinal y 3) LF in situ. Patólogos y clínicos debemos considerar estas patologías cuando se decide el diagnóstico y el tratamiento. La transformación histológica se refiere al evento biológico que lleva al desarrollo de un Linfoma No Hodgkin agresivo de alto grado en pacientes con un LF subyacente. El Linfoma Folicular (LF) pediátrico es una neoplasia excesivamente rara, que difiere del LF del adulto.

FL is a heterogeneous disease with many different subgroups, in terms of age of onset, organs involved (especially extranodal sites) and genetic abnormalities. With great variations in the clinical course, sometimes very indolent or not; can show transformation to high-grade lymphomas, transformations to Diffuse Large B Cell Lymphoma (this being the most common), Burkitt's, Leukemia / Lymphoma, Lymphoblastic. Lymphoma (reported rarely), with an aggressive clinical course have been reported. In 2008 the WHO established 3 new variants: 1) Pediatric FL, 2) Intestinal Primary FL and 3) in situ FL. Pathologists and clinicians must consider these pathologies when deciding on diagnosis and treatment. Histological transformation refers to the biological event that leads to the development of high-grade aggressive Non-Hodgkin's Lymphoma in patients with an underlying FL. Pediatric Follicular Lymphoma (FL) is an excessively rare neoplasm, which differs from adult FL.

Transplante de células-tronco hematopoéticas alogênico com regime de condicionamento de intensidade reduzida em linfoma folicular refratário ou recaído: uma alternativa promissora / Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimen in refractory or relapsed follicular lymphoma: a promising alternative

O linfoma folicular é um tipo de linfoma não Hodgkin de células B indolente. Apenas 30% dos pacientes apresentam doença em fase inicial ao diagnóstico. Os pacientes com estadiamento III-IV estão entre a maioria dos diagnósticos da doença e apresentam altas taxas de recaída ou refratariedade ao tratamento. O linfoma folicular recaído ou refratário permanece um desafio para a prática clínica. O transplante de células-tronco hematopoéticas autólogo vem sendo utilizado há muito tempo nesse perfil de pacientes, com altos índices de complicações como segunda neoplasia e curto período de remissão. O transplante de células-tronco hematopoéticas alogênico com regime de condicionamento mieloablativo apresenta resultados pouco aceitáveis, devido ao aumento da mortalidade relacionada ao tratamento sem benefícios em sobrevida global, da sobrevida livre de doença ou da taxa de recaída que sustentem tal indicação O transplante de células-tronco hematopoéticas alogênico com regime de condicionamento com intensidade reduzida parece ser uma alternativa promissora, inclusive como primeiro transplante. Alguns estudos comparando os resultados dos três tipos de transplantes em pacientes com linfoma folicular recaído ou refratário, com enfoque principal no transplante de células-tronco hematopoéticas alogênico de condicionamento com intensidade reduzida, são descritos neste artigo de revisão.(AU)

Follicular Lymphoma is a type of indolent B-cell non-Hodgkin´s lymphoma. Only 30% of the patients present with an early phase of the disease at diagnosis. Patients with stage III-IV are among the majority of the diagnoses of the disease, and these have high rates of relapse or refractoriness to treatment. Relapsed or refractory follicular lymphoma remains a challenge for clinical practice. Autologous hematopoietic stem cell transplantation has been used for a long time in this profile of patients, with high rates of complications, such as second neoplasia and short remission period. The allogenic hematopoietic stem cell transplantation with myeloablative conditioning regimen presents poorly acceptable results due to increased treatment-related mortality with no overall survival benefits, disease-free survival, or relapse rate to warrant it. Allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning regimen seems to be a promising alternative, even as the first transplant. Some studies comparing the results of the three types of transplants in patients with relapsed or refractory follicular lymphoma , with a main focus on hematopoietic stem cell transplantation allogenic with reduced-intensity conditioning regimen, will be described in this review article.(AU)

Primary cutaneous follicle center lymphoma

Abstract: Cutaneous lymphomas are classified according to their cellular origin into T-cell lymphoma and B-cell lymphoma. The annual incidence rate is 0.3 per 100,000 population. We report a case of a 56-year-old male patient who presented with a two-month history of nodules of varying sizes, some ulcerated, on the face, abdomen, and upper limbs. Histopathological examination and immunohistochemical study confirmed the diagnosis of primary cutaneous centrofollicular lymphoma. Studies have shown an increased incidence of non-Hodgkin lymphomas in the last decade. We report an infrequent case that should be kept as a differential diagnosis of patients with nodules and cutaneous papules.

Linfoma cutáneo primario de células B centrofolicular: un desafío diagnóstico / Primary cutaneous follicular B-cell lymphoma: a diagnostic challenge

El linfoma cutáneo primario de células B (LCPCB) centrofolicular corresponde a una proliferación neoplásica infrecuente e indolente de células del centro germinal confinadas a la piel. Se reporta y revisa un caso de LCPCB centrofolicular. Paciente femenino de 76 años, con antecedentes de hipertensión arterial y resistencia a la insulina. Consultó por aumento de volumen frontal de dos años de evolución. Al examen físico destacaba un nódulo único en región frontal derecha. La ecografía de partes blandas fue compatible con quiste epidérmico. La histopatología demostró en dermis profunda, tejido adiposo subcutáneo y tejido muscular estriado una proliferación linfoide sólida dispuesta en patrón nodular y difuso. A la inmunohistoquímica (IHQ), los linfocitos fueron CD20 y BCL-6 positivo, con un Ki-67 de 60% y BCL-2, CD3, CD5 y CD10 negativo. El estudio de diseminación tumoral resultó negativo. El LCPCB centrofolicular concentra el 60% de todos los LCPCB. Se presenta en promedio a los 51 años. Se ha descrito asociación con Borrelia burgdorferi, VIH, virus hepatitis C y virus Epstein-Barr. Clínicamente corresponde a un nódulo eritematoso y asintomático, localizado preferentemente en cabeza, cuello y tronco. La IHQ es fundamental para diferenciarlo de otros tipos de LCPCB. Habitualmente, el tratamiento es con radioterapia o cirugía escisional. La supervivencia es de un 95% a 5 años. Se presenta este caso dado que el LCPCB centrofolicular corresponde a un tumor cutáneo infrecuente, con múltiples diagnósticos diferenciales, que requiere de un alto índice de sospecha para lograr un diagnóstico y tratamiento oportuno.

The primary cutaneous follicle center lymphoma (PCFCL) corresponds to an infrequent and indolent neoplastic proliferation of germinal center cells confined to the skin. A case of PCFCL is reported and revised. Results: A female patient, 76 years old, with arterial hypertension and insulin resistance. Sough attention for an increase in size of the frontal region over the course of two years. Upon physical examination, a single nodule was noted in the right frontal region. A soft tissue ultrasound identified results indicative of an epidermal cyst. The histopathology revealed a proliferation of solid lymphoid arrayed in a diffuse and nodular pattern in the deep dermis, subcutaneous adipose tissue, and striated muscular tissue. Immunohistochemistry (IHQ) revealed CD20 and BCL-6 positive lymphocytes, with 60% of Ki-67 and BCL-2, CD3, CD5, and CD10 negative. A study of tumor dissemination resulted negative. The PCFCL concentrates 60% of all primary cutaneous B cell lymphomas (PCBCL). It presents at an average of 51 years of age. It has been described association with Borrelia burgdorferi, HIV, hepatitis C virus and Epstein-Barr virus. Clinically it corresponds to an erythematous and asymptomatic nodule, found frequently on the head, neck and trunk. The IHQ is essential to differentiate it from other types of PCBCL. It is usually treated with radiotherapy or excisional surgery. Survival is 95% over 5 years. This case is presented because the PCFCL corresponds to an infrequent cutaneous tumor, with multiple differential diagnoses, requiring a high index of suspicion to achieve an opportune diagnostic and treatment.

Primary cutaneous follicle center lymphoma simulating basal-cell carcinoma on the nasal ala

Primary cutaneous B-cell lymphomas (PCBCLs) constitute 25% of all primary cutaneous lymphomas. They present in the skin with no evidence of systemic or extracutaneous disease at the time of diagnosis, after adequate staging. Primary cutaneous B-cell lymphomas differ significantly from their nodal counterparts in relation to both clinical behavior and prognosis. The distinction between primary and secondary B-cell lymphomas is essential for defining prognosis/course of action. Such distinction is also very difficult to make, since primary and secondary B-cell lymphomas are clinically and histologically indistinguishable. We report the case of a patient with primary cutaneous follicle center lymphoma who underwent surgical excision.

Endoscopic findings of primary follicular lymphoma / Hallazgo endoscópico de linfoma folicular primario

A 79-year-old female with benign past medical history presented to the gastroenterology clinic complaining of long-standing symptoms of dyspepsia. Esophagogastroduodenoscopy showed nodular smooth mucosa in the second part of the duodenum. The morphologic and immunophenotypic findings were consistent with low-grade follicular lymphoma. The purpose of this manuscript is to educate the reader on this unusual finding that is pathognomonic for gastrointestinal lymphoma.

Una mujer de 79 años, sin antecedentes patológicos de importancia, consultó al servicio de gastro enterología por síntomas de dispepsia de larga data. Se practicó una esofagogastroduodenoscopia en la que se observó mucosa nodular en la segunda porción del duodeno. Esta morfología y los hallazgos inmunofenotípicos eran indicativos de linfoma folicular de bajo grado. El propósito de este manuscrito es ilustrar al lector sobre esta inusual condición en el duodeno, la cual es patognomónica de linfoma.

In situ follicular neoplasia/lymphoma: Three illustrative cases exemplifying unique disease presentations.

We report three elderly patients with follicular lymphoma in situ (FLIS) each highlighting a unique pattern of disease presentation and progression. The first patient had incidentally detected FLIS with peripheral blood spill and yet had an 11-year uneventful follow up. The second patient with an overt follicular lymphoma (FL) developed high-grade transformation in jejunum with FLIS extensively involving the Payers patches. The third patient had a FLIS but that qualified as higher grade and was treated in spite of lack of overt FL mainly because of higher grade and patient subsequently did develop overt FL. The first case of typical FLIS confirms that peripheral blood spill does not connote poor prognosis in FLIS, the second case illustrates that FLIS may colonize mucosa-associated lymphoid tissue as part of homing in process of a disseminated FL and the third case validates the aggressive nature of high-grade FLIS.

Risk stratification for indolent lymphomas / Estratificação de risco dos linfomas indolentes

Indolent B-cell lymphomas account for approximately 40 percent of all non-Hodgkin lymphomas (NHLs). Advances in technology have contributed to improvements in the diagnosis and classification of indolent non-Hodgkin lymphomas. Follicular Lymphomas are the most common although the frequency varies significantly throughout the world. The description of the Follicular Lymphoma International Prognostic Index (FLIPI) was an important step in identifying patient subgroups, but its use in the clinical practice has not been established yet. The use of a larger number of paraffin active monoclonal antibodies for immunohistochemistry, molecular cytogenetic studies including standard cytogenetics, multi-color fluorescence in-situ hybridization (FISH), polymerase chain reaction and locus-specific fluorescence insitu hybridization as well as developments in high-resolution techniquesincluding microarray gene expression profiling allow more accurate diagnosis andprecise definition of biomarkers of value in risk stratification. The identification ofdiseasespecific gene lists resulting from expression profiling provides a number ofpotential protein targets that can be validated using immunohistochemistry. Analysesof gene expression profiles or constitutive gene variations may also provide additional insight for prognostication in the near future. A comprehensive understanding of the biology of these distinct lymphoid tumors will allow us to identify novel diseaserelated genes and should facilitate the development of improved diagnosis, outcome prediction, and personalized approaches to treatment.

Os linfomas de células B indolentes representam aproximadamente 40 por cento do total de linfomas não Hodgkin (LNHs). O avanço das tecnologias novas tem contribuído para a melhora no diagnóstico e classificação dos LNH indolentes. O linfoma folicular é o mais comum e sua frequência varia significantemente pelo mundo. Adescrição do Índice Internacional de Prognóstico dos linfomas folicular (FLIPI) representa um passo importante na identificação de subgrupos de pacientes, mas seu uso na prática clínica ainda necessita ser estabelecido. O uso de um número maior de anticorpos monoclonais para imunoistoquímica, estudo citogenético incluindo citogenética convencional ou hibridização in-situ por fluorescência (FISH), bem como o desenvolvimento de técnicas de alta resolução incluindo a expressão por microarray possibilita maior acurácia no diagnóstico e definição precisa dos biomarcadores com valor na estratificação de risco. A identificação de genes específicos para os diversos tipos de linfomas permite o reconhecimento de potenciais proteínas alvo que podem ser validadas usando imunoistoquímica. Análises da expressão do perfil de genes ou variações genéticas constitutivas pode também prover conhecimentos adicionais para o prognóstico em um futuro próximo. Um entendimento da biologia desses distintos tumores linfoides permite-nos identificar novos grupos de genes relacionados à doença e deve facilitar o desenvolvimento diagnóstico, predizendo a evolução e permitindo tratamentos personalizados.

Cellular Density Evaluation for Malignant Lymphoma Using Equivalent Cross-Relaxation Rate Imaging - Initial Experience

OBJECTIVE: Equivalent cross-relaxation rate (ECR) imaging is an MRI technique used to evaluate quantitatively a change in the protein-water interaction. We aimed to evaluate retrospectively the usefulness of ECR imaging for the histologic classification of malignant lymphoma (ML). MATERIALS AND METHODS: Institutional Review Board approval was obtained and all patients provided informed consent. The study subjects included 15 patients with untreated ML who were histologically diagnosed with follicular lymphoma (FL; n = 8) or diffuse large B-cell lymphoma (DLBCL; n = 7). All patients underwent ECR imaging and the offset frequency was set at 7 ppm. RESULTS: The median ECR values were 71% (range; 60.7 to 75.5) in FL and 54% (50.8 to 59.4) in DLBCL (p = 0.001). The median cellular density was 1.5 +/- 0.17 x 10(6) / mm2 in FL and 1.0 +/- 0.70 x 10(6) / mm2 in DLBCL (p = 0.001). The correlation coefficient between the ECR values and cellular density in ML was 0.88 (p = 0.001). In FL and DLBCL, assuming ECR value cut-off points of 60%, both sensitivity and specificity were 100%. CONCLUSION: A strong correlation between ECR and cellular density in ML is demonstrated and the ECR may be a useful technique to differentiate between FL and DLBCL.

Tumor de colisión: Metástasis de adenocarcinoma y linfoma folicular en un mismo ganglio linfático / Colusion tumor consisting in a metastatic adenocarcinoma ano follicular lymphoma in the same lymph node: Report of one case

Colusion tumors are defined as the simultaneous presence of two adjacent but histologically distinct tumor types artsing in the same organ or site. The occurrence of these tumors is rare. We report a 52 year-old woman with a colusión tumor consisting of metastatic adenocarcinoma and follicular lymphoma present in the same lymph node, excised from the left supraclavicular space. The patient died four weeks after the diagnosis was made.

Procesos linfoides B cutáneos con patrón nodular / Cutaneous B cell processes with nodular pattern

Cutaneous lymphomas are low grade malignant neoplasms with favourable prognosis. Those related to the germinal centre with nodular pattern may be: follicular lymphomas (LFC) or extranodal marginal zone B-cell lymphomas (LMC). They are difficult to tell apart, and from reactive processes like cutaneous follicular hyperplasia and cutis immunocytomas. The objective of this study was to check the incidence and the value of both histology and immunohistochemistry in differential diagnosis. Fifty six patients with cutaneous lymphomas were selected within the period 1995-2004. The biopsies were studied with hematoxilin eosin and immunohistochemistry. Thirty two out of the fifty six cutaneous lymphoid infiltrates were of T origin (57.1%) and twenty four of B origin (42.8%), ten out of this last figure (17.7%) were lymphoid processes with nodular pattern Four LFC, three LMC and three HLC were diagnosed. Convergent follicles with scarce mantle and germinal centres with monomorph celullarity were observed in the LFC. Among the LMC, follicles with prominent mantle and nests of monocitoid cells in the mantle, interfollicular zone and in the germinal centers observed. In the HLC macrophages with detritus were found in the germinal centers. LFC showed: CD20 (+), CD 10 (+), bcl-2 (+) or (-), and bcl-6 (+) in the follicle and in the interfollicular area. LMC showed: CD 20 (+), bcl-2 (-), CD 10 (+/-), and bcl-6 (+) in the follicle, and bcl-2 (+), CD10 (-/+) and bcl-6 (-) in the interfollicular area. The HLC results were: bcl-2 (-), bcl-6 (+) and CD 10 (-) in the follicle and bcl-2 (+), bcl-6 (-) and CD 10 (-) in the interfollicular zone. We conclude that lymphoid B cell processes with nodular pattern are unusual. Histology and immunohistochemistry proved to be useful in the differential diagnosis of these lymphomas, and for differentiating these from lymphoid hyperplasias or non tumoral hyperplasias.

Grading of follicular lymphoma using flow cytometry

The treatment and prognosis of follicular lymphoma [FL] is dependant on the grade of the disease. In the World Health Organization classification of lymphoma, grading of FL into low grade [1 and 2] and high grade [3] is recommended. Grading of FL is possible in excision biopsy; histological grading is subjective and inconsistent Grading is extremely difficult in needle core biopsies and fine needle aspirates. We attempted to grade FL using flow cytometry [FCM] and CD 19/forward scatter. Cases of FL seen in our institution and submitted for FCM were evaluated for the percentage of cells detected beyond the 500-channel mark [on a 1024 scale] on a CD19/forward scatter dot plot. We hypothesized that these cells most likely represent centroblasts and their percentage would reflect the grade of the disease. Histological grading of the lymphoma on the open biopsies constituted the reference for FL grade. Thirty-six cases of FL, including 22 males and 14 females, ranging in age from 19 to 92 years [median, 42 years], were studied. There were 17 cases of low grade [grade 1; n=10 and grade 2; n=7] and 19 cases of high grade [grade 3] FL The percentage of cells identified beyond the 500-channel mark on CD19/forward scatter dot plot ranged from 0.12% to 12.55% [median, 4.9%] in low grade [grade 1 and 2] whereas the percentage of those cells in high grade FL ranged from 6.22% to 51.95% [median, 21%; p=0.00001]. Our findings suggest that using a CD19/forward scatter dot plot can help identify centroblasts in FL making grading possible on FCM, especially in small biopsies and fine needle aspirates

Intra-abdominal follicular dendritic cell tumor: report of two cases.

Follicular dendritic cell (FDC) tumor is an uncommon entity described mainly in the lymph nodes. We report two men with intra-abdominal FDC tumors--one arising from the colon and other presenting as a mesenteric mass. Both patients underwent successful surgical excision of the tumor.

Follicular lymphoma: diagnostic value of Kappa/Lambda light chain mRNA restriction by in Situ hybridization

This study was initiated to test the validity of in situ hybridization [ISH] for kappa/lambda light chain mRNA restriction in the diagnosis of FL and compare its value with that of Bcl-2 oncoprotein immunodetection. This work comprised formalin fixed paraffin embedded tissues from 36 lymph node biopsies including 31 cases morphologically consistent with FL and five cases of reactive follicular hyperplasia [RFH] taken as control. Thirty out of 31 FL cases showed a restriction to either kappa or lambda light chain mRNA. Sixteen cases showed kappa restriction, whereas lambda restriction was seen in 14 cases. All lymph nodes with RFH demonstrated a strong hybridization signal with both kappa and lambda oligonucleotide probes. BCL-2 oncoprotein was detected in neoplastic follicles in 20 out of 31 FL cases and was negative in germinal centers of all RFH cases