Plasmocytoid Cells Research Articles

Histopathological Markers for Target Therapies in Primary Cutaneous Lymphomas.

In recent years, targeted (biological) therapies have become available also for primary cutaneous T-cell lymphomas (PCTCLs) including anti-CD30 (brentuximab vedotin) in mycosis fungoides, primary cutaneous anaplastic large T-cell lymphoma, lymphomatoid papulosis; anti-CCR4 (mogamulizumab) in Sezary syndrome; anti-CD123 (tagraxofusp) in blastic plasmocytoid cell neoplasm. Moreover, anti-PD1 (nivolumab), anti-PDL1 (pembrolizumab, atezolizumab), anti-CD52 (alemtuzumab), anti-KIR3DL2-CD158k (lacutamab), and anti-CD70 (cusatuzumab) have been tested or are under investigations in phase II trials. The expression of these epitopes on neoplastic cells in skin biopsies or blood samples plays a central role in the management of PCTCL patients. This narrative review aims to provide readers with an update on the latest advances in the newest therapeutic options for PCTCLs.

REPORT CASE STUDY AND REVEIW LITERATURE: A BENIGN MYOEPITHELIOMA OF THE LUNG

Introduction: Benign myoepithelioma is extremely rare tumor in the lung, there are little cases having been reported in the literature in all over the world, and no report in Vietnam. Case report: A 33-years woman have fever and dry cough from 6 months before entering the hospital, she were treated at home, her fever was gone but the coughing isnot stop, and increasing dyspnea and chest pain. The blood tests is almost in the normal range. Chest CT-scanner showed the tumor in the central bronchial tubes, endoscopy was defined the tumor made the obstruction for the caliber of the left bronchial and designated to remove it by bronchialendoscopy. Histologically, there was mixed of spindle cells, plasmocytoid cells, epithelial cell and clear cells. No mitotic activity or necrosis was seen. Immuhistochemically, the tumor cells positive for EMA, VIII factor, vimentine, and S100 protein. They were negatives for cytokeratine, desmin, CD31, CD34 and GFAP. The diagnosis was benign myoepithelioma of the lung. The patient recovered well after surgery. Conclusion: Benign myoepithelioma is a rare pulmonary tumor, used to differentiate when diagnosing for single lung nodules. This tumor usually distinct from pleomorphic adenoma. Key words: Benign myoepithelioma, lung, lung nodules

Bleeding Polyps?

Bleeding Polyps?

Cervical extramedullary lymphomatoid granulomatosis

Lymphomatoid granulomatosis (LYG) is a rare multisystem disease involving most frequently the lung, kidney and skin. LYG is characterized by an infiltration of atypical lymphocytoid and plasmocytoid cells, with granulomatous inflammation in an angiocentric and angiodestructive pattern. There have been only a few reports of spinal involvement of LYG. To our knowledge, we report the first patient with cervical extramedullary LYG undergoing surgical removal of a lesion causing spinal cord compression, and review the pertinent literature. The patient underwent C5-partial T1 laminectomy with partial removal of the lesion and decompression of the spinal cord. A diagnosis of a grade III LYG was made and chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) was administered. The patient was in good neurological condition at the 6-month follow-up but died 5 months later because of systemic progression of the disease. Although prognosis of LYG remains poor, surgery can be considered to improve pain relief and neurological morbidity of spinal LYG.

Myoepithelioma of the Soft Palate: a Case Report Giving Special Attention to the Differential Diagnosis

ABSTRACTBackgroundMyoepitheliomas are rare tumours that may generally arise from the minor or major salivary glands. The differential diagnosis of this tumour should be performed along with several benign and malignant soft tissue neoplasms. The present case report describes an asymptomatic mass that arose in the soft palate of 42 year old black woman with duration of the six months.MethodsAn incisional biopsy of soft palate lesion was carried out and submitted for histological evaluation under the clinical hypothesis of salivary gland tumour. To confirm the myoepithelial nature of neoplastic cells the immunohistochemical reactions for smooth-muscle actin, cytokeratins and S100 were performed.ResultsThe histological examination revealed the presence of tumour originating from a minor salivary gland and covered by a stratified squamous oral epithelium. The tumour cells were arranged in order to form a myxoid pattern and, individually, small and/or medium spindle-shaped cells with predominantly round or ovoid nuclei, as well as epithelioid and plasmocytoid cells were noted. The stroma was myxomatous and no ductal or syringomatous epithelial structures were observed. Following the histological and immunohistochemical diagnosis of myoepithelioma, the lesion was surgically removed. After the surgery, a follow-up of one year showed no signs and symptoms of reccurrence.ConclusionsThe myoepithelioma should be carefully distinguished from the other soft tissue tumours, especially those arising from salivary glands, such as pleomorphic adenoma and adenoid-cystic carcinoma.

Overexpression of TOSO in CLL Is Triggered by B-Cell Receptor Signaling and Associated with Progressive Disease.

Resistance towards apoptotic stimuli mediated by overexpression of antiapoptotic factors or extracellular survival signals like B-cell receptor stimulation (BCR) are considered to be responsible for accumulation of malignant B cells in CLL . TOSO, also known as Fas-inhibitory molecule 3 (FAIM3), was identified as overexpressed candidate gene in CLL based on re-evaluation of publicly available microarray data sets. Based on primary CLL samples from 106 patients, TOSO expression was compared to healthy donor B cells using quantitative real-time PCR, western-blot, flow cytometry and immunohistochemistry. To reveal underlying mechanisms of TOSO overexpression, B-cell receptor (BCR) and CD40Ligand stimulation as well as bone marrow stroma cell co-incubation was performed. Apoptotic resistance was assessed by annexin V/7-AAD flow cytometry in context of CH11-Fas-agonistic antibody. TOSO was identified to exhibit elevated relative expression of 6.8 compared to healthy donor B cells using quantitative real-time PCR (p=0.004). High levels of TOSO expression in CLL correlated with high leukocyte count, advanced Binet stage, previous need for chemotherapy and unmutated IgVH status. CD38+ CLL subsets harboring proliferative activity showed significantly enhanced TOSO expression. Immunohistochemistry revealed upregulation of TOSO in lymph nodes of CLL patients. In lymph nodes derived from healthy donors TOSO was detected in single plasmocytoid cells within the germinal center and in the marginal zone. No specific staining was seen in follicular lymphomas. CLL-specific upregulation of TOSO was confirmed by RT-PCR, samples of follicular lymphomas, DLBCL, marginal zone lymphoma and Hodgkin cell lines did not reveal TOSO up-regulation. We evaluated functional mechanisms of aberrant TOSO expression in CLL cells and identified TOSO expression significantly being induced by BCR-stimulation compared to control cells (relative expression (RE) 8.25 vs. 4.86, p=0.013). In contrast, CD40L signaling significantly reduced TOSO expression (RE 2.60; p=0.007). Spontaneous apoptosis of CLL cells was significantly reduced by BCR-stimulus, in CD40Ligandstimulated CLL samples a slight sensitization towards Fas-mediated apoptosis was seen. In summary, we show that the anti-apoptotic factor TOSO is associated with progressive disease and enhanced in the proliferative CD38+ cell subset. Both association with unmutated IgVH and the specific induction of TOSO via the BCR suggest autoreactive BCR signaling as a key mediator of apoptosis resistance in CLL. Down-regulation of TOSO by CD40Ligand in the context of CD40Ligand-mediated Fas-sensitization of CLL reveal TOSO as a new anti-apoptotic factor in CLL. CLL-specific over-expression of the transmembrane protein might further offer new therapeutic strategies in CLL treatment.

FDG PET/CT findings in acute adult mononucleosis mimicking malignant lymphoma

We report a case of acute Epstein-Barr virus (EBV) infection in which the clinical syndrome and pattern of F-18-2-fluoro-2-deoxy-D-glucose (FDG) uptake mimicked malignant lymphoma. A 53-yr-old man presented with 2 wk of high fevers, night sweats, sinus congestion and severe fatigue. The patient was treated for 1 wk with broad-spectrum antibiotics for acute sinusitis without any improvement. Persistence of fevers and presence of abnormal lymphadenopathy seen on the abdominal computed tomography (CT) were concerning lymphoma with B symptoms. FDG positron emission tomography (PET) showed avid FDG uptake in numerous abdominal/pelvic nodes, liver, spleen and bone marrow. These findings were highly suspicious for lymphoma. Patient underwent a pelvic lymph node biopsy which showed large granular lymphocytes that were predominantly T cells. Bone marrow biopsy showed diffuse infiltration with plasmocytoid cells that were not kappa lambda restricted. Additional diagnostic workup became available showing positive EBV IgM titers and negative IgG levels indicating acute infectious mononucleosis. Lymph node biopsy stained positively with EBV-encoded RNA. We concluded that patient's abnormal FDG PET was most likely secondary to acute EBV infection. After 2 months, follow-up FDG PET/CT showed marked improvement in lymphadenopathy and decreased hypermetabolic activity in the liver and spleen. Other than EBV, there are many other FDG-avid non-malignant conditions that may lead to false-positive PET scans. FDG accumulates in inflamed and infected lesions with increased glucose metabolism. This case underscores the importance of maintaining a broad differential and restricting use of PET scans for staging.

Pseudoangiosarcomatous features in medullary thyroid carcinoma spindle‐cell variant. Report of a case studied by FNA and immunohistochemistry

We report a case of medullary thyroid carcinoma (MTC), spindle cell variant, which exhibited striking histological pseudovascular clefts and abortive lumina, closely mimicking an angiosarcoma. The patient is a 72-yr-old-man who presented facial rash and a solid nodule in the right lobe of the thyroid gland. The fine-needle aspiration (FNA) showed bloody background containing loosely groups of fusiform and plasmocytoid cells with coarse chromatin and eosinophilic granular cytoplasms. Microscopically, the tumor exhibited spindle-cell pattern intermingled with a striking angiosarcoma-like pattern characterized by the presence of abortive lumen and clefts containing erythrocytes. Dense hyaline extracellular amyloid was present. The tumor cells were strongly positive for cytokeratin, chromogranine-A, synaptophysine, serotonin, calcitonin, and CEA. TTF-1 was weakly positive. Stains for CD34 and CD31 were negative. This case illustrates that the spindle cell variant of MTC may exhibit an infrequent angiosarcoma-like appearance which may be misdiagnosed as angiosarcoma.

Mioepitelioma de glândula salivar menor: uma análise imunohistoquímica de quatro casos

INTRODUÇÃO E METODOLOGIA: Realizou-se um estudo imunohistoquímico em 4 casos de mioepiteliomas, visando traçar seu perfil quanto ao grau de diferenciação das células através dos anticorpos alfa-SMA, CK 14 e vimentina, bem como investigar o índice de proliferação celular pelo anti-PCNA, além de comparamos a imunorreatividade com o tecido glandular normal adjacente ao tumor. RESULTADOS: No tecido glandular normal as células mioepiteliais exibiram marcação para alfa-SMA e CK 14, enquanto que nas células ductais somente a presença da CK 14 foi verificada. Em todos os casos foi verificada positividade para CK 14 e vimentina, porém a CK 14 esteve presente somente em células epitelióides e fusiformes, enquanto que a vimentina mostrou-se positiva também nas células plasmocitóides. A alfa-SMA não foi detectada nas células neoplásicas. Imunopositividade para o PCNA foi observada em mais de 75% do componente celular dos tumores analisados, independente do tipo. CONCLUSÕES: Concluiu-se que não houve diferença na atividade proliferativa entre os tipos celulares presentes nos mioepiteliomas e, ainda, que os resultados deste estudo sugerem que as células constituintes desta neoplasia realmente representam células da linhagem mioepitelial, mas em diferentes estágios de diferenciação.

Myoepithelioma of minor salivary gland - An immunohistochemical analysis of four cases

SummaryIntroduction and MethodsWe performed an immunohistochemical study in four cases of myopitheliomas with objective to realize a profile in respect of differentiation grade by the monoclonal antibodies CK14, vimentin and alph-SMA, besides to investigate the cell proliferation by anti-PCNA, besides, we compare the immunoreactive with glandular normal tissue.ResultsIn the glandular normal tissue the myoepithelials cells had shown expression for alpha-SMA and CK 14, while that in the ductals cells, only the presence of CK 14 was verified. All the cases was verified positivy for CK 14 and vimentin, however, CK 14 had been present only in epithelioid and fusiform cells, while that the vimentin revealed positive also in the cytoplasm of the plasmocytoid cells. alpha-SMA was not detected in the neoplasic cells. Immunopositivity for the PCNA was observed in more than 75% of the cellular component of the analyzed tumors, independent of the cellular type.ConclusionsWe concluded that it did not have difference in the proliferative activity among the cellular types presents in the myoepitheliomas and, still, the results of this study suggest that the constituent cells of this neoplasia one really represent cells of the mioepitelial ancestry, but in different stages of differentiation.

Myoepitheliale Tumoren der Haut und des Weichgewebes

Myoepithelial neoplasms of skin and soft tissues comprise cutaneous mixed tumor (chondroid syringoma), mixed tumor of subcutaneous and deep soft tissues, myoepithelioma and rare malignant myoepithelioma (myoepithelial carcinoma). Myoepithelial tumors of skin and soft tissues are characterized by an extreme clinicopathological heterogeneity as in other anatomic locations. The neoplasms arise in childhood as well as in adults and are composed of epithelioid, histiocytoid, spindled, plasmocytoid and/or clear tumour cells in varying combinations, and are set in a myxoid or hyalinised intercellular matrix. Immunohistochemically, neoplastic cells stain positively for epithelial markers (pancytokeratin and/or epithelial membrane antigen), and often for S 100 protein. More rarely muscle actin, glial fibrillary acid protein, calponin, and p63 are expressed, whereas desmin is usually negative. The presence of at least moderate cytological atypia is associated with a significant risk for aggressive behavior and propensity for metastasis.

Cutaneous myoepithelial neoplasms: clinicopathologic and immunohistochemical study of 20 cases suggesting a continuous spectrum ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and myoepithelial carcinoma

Myoepithelial neoplasms, both benign and malignant, are rare but well-established clinicopathologic entities in the salivary glands, the breast, and the lung. Despite similarities between cutaneous sweat glands and glandular structures in the above-mentioned organs as well as the presence of regular myoepithelial cells around cutaneous eccrine/apocrine glands, the concept of cutaneous myoepithelial neoplasms is still debatable and not commonly accepted. Twenty cutaneous myoepithelial neoplasms have been studied histologically and immunohistochemically. Nine neoplasms showed features of benign mixed tumor of the skin (chondroid syringoma) (five females and four males, age range 19-65 years, all cases arose in the head and neck region). Two cases represented the eccrine and seven the apocrine subtype. Interestingly, in three cases of the apocrine subtype, solid areas composed predominantly of myoepithelial cells were detected; these neoplasms were designated as benign mixed tumors with prominent myoepithelial cells. Nine cutaneous neoplasms were composed of spindled, epithelioid, and plasmocytoid cells without ductal differentiation and immunohistochemically stained variably positive for vimentin, epithelial and myogenic markers, S-100 protein, calponin, and glial fibrillary acidic protein (four females and five males, age range 3-71 years, four cases arose in the head and neck region and one case each on the finger, the thigh, the lower leg, the foot, and the breast, respectively); these neoplasms were designated as cutaneous myoepitheliomas. Two morphologically malignant neoplasms with cytologic and immunohistochemical features of myoepithelial cells arose on the face of a 70-year-old female and a 79-year-old male patient; these neoplasms were designated as malignant cutaneous myoepitheliomas (cutaneous myoepithelial carcinomas). The study suggests a continuous spectrum of cutaneous myoepithelial neoplasms ranging from benign mixed tumor of the skin to cutaneous myoepithelioma and cutaneous myoepithelial carcinoma. Further studies with extended follow-up information are necessary to establish prognostic factors.

Dendritic cells in allergy.

Dendritic cells in allergy.

Cytologic Features of Malignant Peripheral Nerve Sheath Tumor

To study the cytomorphologic features of malignant peripheral nerve sheath tumor (MPNST), including the epithelioid cell variant, and to establish differential diagnostic features with benign neurogenic tumors and other sarcomas. Cytologic smears from primary, recurrent and metastatic tumors in 10 patients with MPNST were reviewed. Three patients had neurofibromatosis 1 (NF1), and in two others the tumor arose from a preexisting neurofibroma. Immunocytochemical evaluation of S-100 protein was performed in four cases. A complete pathologic study was available in all cases. To assess the validity of morphologic recognition, a blinded study, including eight cases of spindle MPNST among smears from histologically proven schwannomas, synovial sarcomas, leiomyosarcomas, malignant fibrous histiocytomas and liposarcomas, was performed. Neurogenic differentiation was recognizable in four cases (differentiated), while the other four (anaplastic) were indistinguishable from other pleomorphic sarcomas. The presence of elongated, slender, often wavy nuclei and less commonly a delicate, fibrillary metachromatic stroma were features suggestive of nerve sheath differentiation. Other cytologic, as well as clinical, features permitted their identification as malignant. Two cases of epithelioid MPNST disclosed large, polygonal to plasmocytoid tumor cells without specific cytologic features. S-100 immunoexpression was positive in two of the four cytologic samples tested. Although no morphologic findings are specific to MPNST, the above-mentioned cytologic features may suggest, in differentiated cases, its neurogenic differentiation. On the basis of morphologic features alone, the diagnosis of anaplastic and epithelioid MPNST is not possible, and immunocytochemical and ultrastructural studies are necessary. A specific cytodiagnosis is possible in recurrences, metastases and cases of NF1 or a preexisting neurofibroma.

An ultrastructural study of nodular amyloidosis of the tongue

We have treated a patient with a nodular amyloidosis in the center of the dorsum of the tongue. Ultrastructural observations of human amyloidosis have been reported by many investigators, but there have been few reports of nodular amyloidosis of the tongue. Ultrastructural investigation showed a number of amyloid fibrils around and in the plasmocytoid cells, and severe pressure atrophy was found in many stromal cells, especially in endothelial cells.

Immunocytoma of prostate

Prostatic involvement by non-Hodgkin lymphoma is rare. Infiltration of the gland by the uncommon plasmocytoid cells sufficient to cause clinical signs and symptoms of prostatic obstruction is described.

Angioimmunoblastic lymphadenopathy: light and electron microscopic studies.

The present study evaluates the significance of clinical and histologic features in 16 cases of angioimmunoblastic lymphadenopathy (AIL). The disease observed in the elderly is characterized by an acute onset of constitutional symptoms, generalized lymphadenopathy, hepatosplenomegaly, and immunologic abnormalities. The clinical course is rather short, and autopsied cases show severe infections complications. In the present study, two histologic types were identified: 1) Angio-cellular (A-C) type: the lymph nodes contained lymphocytes, immunoblasts, histiocytes, eosinophils and/or plasma cells. 2) Immunoblastic and plasma cell (I & P) type or lymphocyte depleted (LD) type; the lymph node contained mainly immunoblasts and plasmocytoid cells. Serum protein was examined in 12 cases. Dysproteinemia was noted in 5 of 6 cases of A-C type and in 5 of 6 cases of I & P type. There is a definite relationship between histologic types and survival periods. The A-C type is an expression of slight depletion of lymphocytes and the I & P or LD type represents marked depletion of lymphocytes. AIL has malignant potentiality, though it resembles graft-vs-host reaction in histology, the wide-spread involvement of tissues and clinical features. An immunologic investigation on 3 cases suggests that the disease is based on B-cell disorder.

Deuterium isotope effects on lymphoid tissues and humoral antibody responses in mice

Hematological and other morphological changes following body deuteration were evaluated in young adult pathogen-free female Swiss albino mice given heavy water (99.8% D2O) as drinking fluid. Control groups included mice given tap water ad libitum, distilled water, or amounts of tap water equivalent to the reduced fluid intake of animals drinking D2O. Deuterated mice manifested changes in their spontaneous activity, weight loss, fall in body temperature, atactic gait, ruffled fur, decrease in breathing rate and preterminal cachexia. The mice were killed in a moribund state after exposure to D2O for about 2 weeks. At the time of death, packed red blood cell volumes were within normal range. Mean erythrocyte counts were not markedly reduced. In contrast, there was a conspicuous blood lymphocytopenia. The bone marrow displayed a normal cellularity and a moderate reduction in the proportion of erythropoietic cells. A particularly striking weight loss of thymus and spleen, and a marked systemic lymphocyte depletion were apparent, particularly in the thymus, white pulp of the spleen, lymph nodes, and gut-associated lymphoid tissue. Signs of increased cell death were found in lymphoid organs. The number of mitotic figures in intestinal cryt epithelia was reduced. Since D2O is known to interfere with DNA synthesis and mitosis, the deuterium-induced systemic lymphocyte depletion was probably due to disturbed cell proliferation and increased cell death. On the basis of these data, the effects of reduced levels of deuteration on antibody production and thymic morphology were also evaluated. Adult female Swiss albino mice, raised under specific pathogen-free conditions, were given drinking fluids composed of 10%, 20% and 40% D2O during the experimental test period. After 7 days exposure, all animals were given a primary subcutaneous injection of tetanus toxoid, followed by a booster injection 49 days after primary stimulation. All animals were killed 7 days after the booster. Deuteration resulted in a dose-dependent depression of specific antibody production. Primary antitoxin responses were more affected than secondary responses. A marked reduction of the thymic cortical area of deuterated mice was proportional to the dose of D2O. Deuterium-induced immunosuppression is tentatively linked to a diminution of the total body lymphoid cell mass and suppression of the plasmocytoid cells involved in antibody synthesis.

KAPPA‐TYPE LIGHT CHAIN CRYSTAL STORAGE HISTIOCYTOSIS

An autopsy case of systemic histiocytosis with excessive deposition of kappa-type light chain crystals was reported in a 58 year-old man who had consistently showed kappa-type light chain paraproteinemia, Bence Jones proteinuria and hypogammaglobulinemia for about 10 years until his death. However, no bony destruction was found by repeated X-ray examinations. At autopsy, extensive hyperplasia of crystal-storing histiocytes was observed in the bone marrow, spleen, liver, lymph nodes, interstitial tissues of visceral organs and loose connective tissues. In the bone marrow and some other tissues, mild proliferation of plasmocytoid cells containing small crystals were found. Histochemically the crystals positively stained with various methods for amino acids and proteins, especially with Weigerts' method for fibrin. Ultrastructurally intralysosomal crystal deposition was confirmed in the storage histiocytes and derivation of the crystals from Golgi's sacculi in the plasmocytoid cells was suggested. Biochemically the crystals were regarded as mainly consisting of dimers of a variable half of light chain immunoglobulin and immunochemically and immunohistochemically reacted to anti-kappa type light chain serum. Such a generalized storage histiocytosis may be secondarily induced by immunoglobulin synthesized in plasmocytoid cells.

Occurrence of Plasmocytoid Cells in Long-Term Blood-Cell Cultures from a Patient with ‘Hairy Cell’ Leukemia

Cells from the peripheral blood of a patient with 'hairy cell' leukemia were cultivated in long-term cultures. They grew with a monolayer growth pattern and consisted of at least two cell populations. The electron microscopic morphology of the cultivated cells revealed cells resembling 'hairy cells' showing the typical cytoplasmic protrusions and cells with structural characteristics of plasma cells.