Immunophenotyping of mature T/NK cell neoplasm presenting as leukemia.

Introduction : Mature T/NK cell lymphomas (MTNKL) presenting as leukemia are rare and show considerable overlapping of clinical, morphological and immunophenotypic features. AIM: Critical analysis of the morphology and immunophenotypic profile of MTNKL. Materials and Methods : We reviewed 380 consecutive cases of mature lymphoid neoplasm that presented as leukemia and were diagnosed on morphology and immunophenotyping of bone marrow and/or peripheral blood samples. Results : Peripheral blood and bone marrow involvement was seen in all cases. MTNKL constituted 4% (nine cases) of all mature lymphoid neoplasms presenting as leukemia. It included four cases of T-large granular leukemia (T-LGL), two of T-cell prolymphocytic leukemia small cell variant (T-PLL), two of adult T-cell leukemia/lymphoma (ATLL) and one of primary cutaneous gamma delta T-cell lymphoma (PCGDTCL). T-LGL revealed CD4-/CD8+ phenotype in three, and CD4+/CD8+ phenotype in one case. CD56 was absent in all the cases of T-LGL. One case of T- PLL small cell variant showed CD4+/CD8- phenotype, while the other revealed CD4-/CD8+ phenotype. Both cases of ATLL showed CD4+/CD8+/CD25+ phenotype. The single case of PCGDTCL showed CD4-/CD8- phenotype pattern. CD3 and CD5 were expressed in all MTNKL. CD7 was absent in three cases of T-LGL. TCRα/β was performed in three cases of T-LGL and was positive in all. TCRα/β was also seen in both the cases of T-PLL small variant. However, TCRα/β was seen in the single case of PCGDTCL. Conclusion : Mature nodal T/NK cell neoplasms are rare and MTNKL presenting as leukemia are even rarer. There is an overlap between the immunophenotypic profiles of different MTNKL subtypes and elaborate T/NK cell panels are required for their evaluation.

Linfoma CutáneoT/NK tipo nasal símil hidroa vacciniforme / Hydroa-like cutaneous T/NK-cell lymphoma, nasal type

El linfoma T/NK cutáneo símil hidroa vacciniforme (HV) es un linfoma poco común que afecta principalmente a niños asiáticos e indoamericanos. Se inicia con edema, vesículas, costras y cicatrices de tipo vacciniforme. De evolución prolongada, tiende a agravarse con los años, desfigurando y comprometiendo física y psíquicamente al paciente. Debido a la detección tardía del linfoma, en general el pronóstico de vida de estos pacientes es malo. Se presenta una paciente de 20 años con linfoma NK de tipo nasal, que comenzó a los 13 años con un cuadro de HV de mala evolución. Los autores proponen que en pacientes con HV atípica un tratamiento en etapas tempranas de la enfermedad podría mejorar su pronóstico.

The hydroa-like cutaneous T-cell lymphoma is not a very common lymphoma,children from Asia and indoamericans are mainly aff ected. Theybegin with edema, vesicles, crusts and vacciniform scars with a prolongedevolution increasing through to the years. This illness aff ects the patientsphysically and psychologically because of its disfi guring eff ects.Due to the late detection of the lymphoma, generally the prognosis ofthese patients is poor. A patient of 20 years old, who suff ered of NK-celllymphoma nasal type, is presented. She began with hydroa vacciniformeat the age 13 years old, she developed a T/NK lymphoma and died. Theauthors propose that on patients with atypical hydroa vacciniformes, atreatment in earlier stages could off er a better prognosis (Dermatol Argent2009;15(5):350-353).

A Case of T/Natural Killer Cell Lymphoma of the Uterine Cervix / 대한산부인과학회지

Non-Hodgkin's lymphoma presented as a malignancy of the uterine cervix is exceedingly rare disease and accounts for approximately only 0.12-0.6% of extranodal lymphomas. Most reported cases were B-cell lymphomas and there is no consensus on the management and prognosis of the disease because of its extreme rarity. Primary T/natural killer (NK)-cell lymphoma arising from the uterine cervix is scarcely encountered that, in the review of literature, only 1 case has been reported by Mhawech et al. We encountered a woman with T/NK-cell lymphoma involving the uterine cervix that initially presented with severe vaginal bleeding. Therefore, we report the case with a brief review of literature.

Expresión inmunohistoquímica de metaloproteasas (MMP-1, 2 y 11) e inhibidor de metaloproteasas de tejido-1 (TIMP-1), y expresión de p53 en linfomas angiocéntricos de células T/NK tipo nasal / Metalloproteinase (MMP-1, 2 and 11), tissue inhibitor of metalloproteinase-1 (TIMP-1), and p53 expression in nasal-type angiocentric T/NK-cell lymphoma. An immunohistochemical study

Se analizan 20 casos de linfomas extraganglionares de células T/NK de tipo nasal, estudiados en el Instituto Nacional de Cancerología, México, D. F., para su expresión inmunohistoquímica de las células neoplásicas, expresión nuclear de la proteína supresora de tumor p53, así como de enzimas que participan en invasión, destrucción tisular y metástasis: metaloproteasas. Material y métodos: Se estudió el material quirúrgico de estos casos y se efectuó tinción con hematoxilina y eosina analizando sus características histopatológicas: tamaño celular y detalle citológico. Se realizó estudio de inmunohistoquímica para corroborar el tipo celular, así como CD3 (células T), CD56 (células NK), expresión nuclear de la proteína supresora de tumor p53, y la expresión de metaloproteasas tipo 1, 2, 11 (MMP-1, 2, 11) y un inhibidor de metaloproteasas 1 (TIMP-1). Se analizaron variables demográficas, como edad del paciente, sexo, localización del tumor primario, etapa clínica, tratamiento en general y seguimiento. Estudio estadístico: Se analizó la prueba exacta de Fisher para correlacionar la expresión entre las metaloproteasas y su diferencial entre las células epiteliales, tumorales, estromales, necrosis y células endoteliales. Resultados: Los 20 casos fueron positivos CD3 citoplásmico, CD56, 19 de ellos positivos a p53, cinco de ellos con positividad nuclear mayor al 50% de las células neoplásicas. Hubo una mayor expresión citoplásmica tumoral de MMP-1; mayor expresión citoplásmica en el epitelio de TIMP1 y MMP-11. Los pacientes con sobreexpresión de p53 tuvieron un curso clínico fatal. Tres de ellos recibieron únicamente radioterapia falleciendo dentro del primer mes del tratamiento. Discusión: Los linfomas angiocéntricos de células T/NK tipo nasal son neoplasias frecuentes en los países de Asia, Latinoamérica, incluyendo a México. Frecuentemente esta patología se asocia a VEB con expresión fenotípica de células T/NK, cuyas características histológicas son: atipia celular linfoide, angioinvasión y necrosis, reflejado en los pacientes con destrucción progresiva de los tejidos blandos del macizo facial y curso clínico fatal.

Twenty cases of extraganglionar Nasal type T/NK cell lymphomas were analyzed at the National Cancer Institute of Mexico. We studied immunophenotype of neoplastic cells, nuclear p53 expression, and enzymes as matrix metalloproteinases participating in invasion, tissular destruction and metastases. Material and Methods: Paraffin blocks from all cases were retrieved and analyzed by hematoxilin and eosin. Histopathological features included cellular size and cytologic characteristics. We performed immunohisto chemistry to determine CD3, CD56, p53 cellular type and expression of (MMPs-1, 2,11) matrix metalloproteinases and one tissue inhibitor of TIMP 1 metalloproteinase. Demographic variables included, age, sex, primary location, clinical stage, treatment and follow up. Statistical analysis: The association of different matrix metalloproteinases in epithelial and tumoral cells, stroma, necrosis and endothelial cells were found to be significant using Fisher s exact test. Results: All studied cases were positive to cytoplasmic CD3, CD56 (NK cells), 19 of them were positive to p53, five of them with nuclear overexpression of p53 in more than 50% of neoplastic cells. There was significant expression of MMP-1 in tumoral cells; the epithelium displayed significant expression of TIMP 1 and MMP-11. Patients with p53 overexpression displayed a poorer prognosis. Three of them had undergone radiotherapy and died within the first month of treatment. Discussion: This type of lymphoma is a common neoplasm in Asia, Latin America and Mexico. It is worth noting it has has been linked to Epstein Barr virus with T/NK-cell phenotype, which often displays cellular atypia, an angiocentric growth pattern and necrosis. It is clinically expressed by progressive destruction of midline facial soft tissue and has a poor prognosis.

A Case of Nasal T/NK-cell Lymphoma

The advance of the immunobiology clarifies the nature of non-Hodgkin's lymphoma(NHL). In addition the proceed in the immunophenotyping renders the classification of NHL. According to the Revised European American Lymphoma(REAL) classification, classified by the etiologic factors, molecular biological characteristics, immunophenotype, cytogenetics and histologic feature, nasal T/NK-cell lymphoma(=angiocentric lymphoma) belongs to the category of peripheral T-cell and natural killer cell lymphoma. Nasal T/NK-cell lymphoma is a distinct clinicopathologic entity characterized by progressive necrotic lesions in the nasal cavity, nasopharynx, and palate. The cellular origin of this tumor has been controversial. Although most nasal T/NK-cell lymphomas are of NK-cell lineage, being CD56+, negative for surface CD3(Leu4), and unassociated with rearrangements of the T-cell receptor genes, other minor variants have been reported. This lymphoma is a rare disease and usually experienced in adult. Recently, we experienced a rare type lymphoma, nasal T/NK-cell lymphoma, in 14 years old boy. His soft mass occupied the right nasal cavity including the nasal septum and turbinate. Pathologically this nasal mass showed the infiltration into the vascular wall, illustrating angiodestructive lesion. The cellular origin was NK-cell lineage, being CD56+ and negative to CD3. Now, we report the case with a brief review of related literatures.

A Case of Aggressive T/NK-cell Lymphoma/leukemia with Cutaneous Involvement / 대한피부과학회지

Non-nasal T/NK-cell lymphomas(TNKCL) are further subdivided into primary cutaneous and 4 subtypes of secondary cutaneous lymphomas such as nasal type, aggressive, blastic(blastoid), and other specific NK-like T-cell lymphoma. Aggressive T/NK-cell lymphoma/leukemia(ATNKCL) is a rare leukemic variant of nasal type TNKCL. Although ATNKCL invariably exhibits the identical histomorphological, genotypical and immunophenotypical findings with TNKCL, it is distinguishable from the nasal type of TNKCL in that the former reveals atypical cells having large azurophilic cytoplasmic granules in the peripheral blood and bone marrow. We herein report a rare case of ATNKCL with secondary cutaneous lesions.

Therapeutic Outcome of Epstein-Barr Virus Positive T/NK Cell Lymphoma in the Upper Aerodigestive Tract

Expression of the natural killer (NK) cell antigen CD56 is uncommon in malignant lymphoma, but when it is, it is almost exclusively of the non-B cell lineage and show a preference for the nasal and nasopharyngeal region. T/NK cell lymphoma is known to be aggressive and refractory to treatment. It is highly associated with the Epstein-Barr Virus (EBV), but clinical investigations are rarely reported, that is until recently. We report here, on the clinical features and therapeutic outcomes of patients with T/NK cell lymphomas and its association with EBV. We reviewed fifty-four cases with peripheral T cell lymphomas in the upper aerodigestive tract between Jan. 1987 and Aug. 1998 from the Severance Hospital, Yonsei University College of Medicine. The diagnosis of T/NK cell lymphoma was made according to the expression of the NK cell markers, CD56 antigen and cytoplasmic CD3 epsilon, in tumor specimens, by immunohistochemistry. Epstein-Barr early region (EBER) RNA was detected using in situ hybridization on paraffin-embedded sections. Among the 54 cases with malignant lymphomas occurring in the upper aerodigestive tract, 20 had T/NK cell lymphoma (37%). The primary sites of T/NK cell lymphomas were the nasal cavity, 12 cases (60%), the tonsils, 4 cases (20%), the nasopharynx, 2 cases (10%), and the oropharynx, 2 case (10%). There were no differences between the features, at diagnosis or therapeutic modalities for patients with T/NK cell lymphoma and non-T/NK cell lymphoma. The complete remission rate of T/NK cell lymphomas was lower than non-T/NK cell lymphomas (65% vs 85%, p=0.02). The overall survival of T/NK cell lymphomas was 13 months (1-74 month), which was significantly lower than non-T/NK cell lymphomas [60.6% with a median follow up of 22 months (1-101 month, p=0.02)]. Disease free survival of T/NK cell lymphomas was 22 months (4-66 month), significantly lower than non-T/NK cell lymphomas [73.8% with a median follow up of 22 months (2-95 month), p=0.04]. The overall survival rates for T/NK cell lymphomas were significantly lower than for EBV positive non-T/NK cell lymphomas (p=0.018). EBER RNA was detected in the paraffin-embedded tissue sections of all T/NK cell lymphomas, compared to only 17.6% (6 of 34 cases) for non- T/NK cell lymphomas. In conclusion, as patients with T/NK cell lymphomas showed poor clinical outcomes, and a high association with EBV positivity, clinical trials with more investigational therapeutic strategies, and further research into the relationship of EBV infection with pathogenesis of T/NK cell lymphoma is warranted.

A Case of Primary CD56+ T/NK Cell Lymphoma of the Colon / 대한소화기내시경학회지

Primary T/natural killer (NK) cell lymphoma of the colon is extremely rare. Although this tumor is well known to arise in the nasal cavity and upper aerodigestive tract, only a few cases have been reported in the colon as an extranodal disease, which were mainly reported in East Asia. Recently, several authors have described the clinicopathologic, immunophenotypic, and genotypic features of CD56-positive tumor as a distinct subgroup due to its aggressive clinical behavior and poor prognosis. However, primary T/NK cell lymphoma of the colon may present a difficult diagnostic challenge to physicians because the symptoms and colonoscopic findings are non-specific and available data in the literature are very limited. We herein describe a case of primary T/NK cell lymphoma of the colon presenting as ulcerative lesions similar to Crohn's colitis and complicated by cecal bleeding/perforation.

A Case of Nasal-type T/NK-cell Lymphoma Resembling Cellulitis / 대한피부과학회지

T/NK-cell lymphoma shows biphenotype of the T-cell and NK-cell. This tumor is characterized by the absence of clonal rearrangement of T-cell receptor gene, frequent association with Epstein-Barr virus(EBV), poor clinical course, and common extranodal invasion. When the tumor did not involve nasal cavity, it is called nasal-type T/NK-cell lymphoma. It commonly appears as deep nodule, infiltrative plaque, and ulcerative plaque. We describe a case of nasal-type T/NK-cell lymphoma, associated with EBV, and showing clonal T-cell receptor gamma gene rearrangement. The patient was 60-year -old female with a skin lesion on her face, which resembled cellulitis.

A Case of Non-nasal T/NK-cell Lymphoma Occurring in A Patient with Autiphospholipid Syndrome / 대한피부과학회지

Non-nasal T/NK-cell lymphoma(TNKCL) without nasal cavity invasion is a subtype of angiocentric T-cell lymphomas showing the biphenotype of the T-cell and NK-cell. This tumor is characterized by the absence of clonal rearrangement of the T-cell receptor gene, frequent association with Epstein- Barr virus(EBV), poor clinical course, and common extranodal invasion. Antiphospholipid syndrome (APS) is characterized by repetitive spontaneaus abortion, thrombocytopenia, thrombotic symptoms and the positivity to the antiphospholipid antibody. Our patient was a 35-year-old woman with skin lesion on her face. Previously, she had been diagnosed of APS. Histopathological, immunohistochemical and serologic studies could disclose EBV-associated non-nasal TNKCL.

Subcutaneous Panniculitic Angiocentric T/NK-Cell Lymphoma / 대한피부과학회지

Nasal-type T/NK cell lymphoma shows frequent extra-nodal involvement including skin with poor prognosis. Subcutaneous panniculitic T-cell lymphoma which is characterized by subcutaneous nodules, systemic signs and symptoms, and a hemophagocytic syndromes was also identified and must be differentiated with primary cutaneous nasal-type T/NK cell lymphoma. We report a case of subcutaneous angiocentric T/NK cell lymphoma in a 77-year-old man who had multiple deep ulcers on the extremities. Strong CD56 positivity and EBV RNA by in situ hybridization were demonstrated in the angiocentric infiltrates of the subcutis. The skin lesions were resistant to combination chemotherapy and pancreatic involvement of lymphoma developed. One year after onset of the skin lesions, he had a rapid downhill course.

A Case of NCAM-positive Nasal Type T/NK-Cell Lymphoma

We herein report a case of nasal type T/natural killer(NK)-cell lymphoma(TNKCL). This lymphoma is characterized by the expression of CD2, CD43 and NCAM(CD56) antigen, an aggressive clinical course, frequent extranodal spreading, a strong association with Epstein-Barr virus(EBV), and the absence of T-cell receptor(TCR) gene rearrangement. NCAM antigen is known to be a possible determinant of extranodal dissemination of peripheral T-cell lymphoma(PTCL). The patient is a 70-year-old male with skin lesion on his forearm. Histopathological and immunohistochemical studies were diagnostic of EBV-associated TNKCL. Untill now, he has failed to respond to anticancer therapy.