RESUMO
Mycosis fungoides (MF) has been widely reported to mimick a considerable number of different dermatoses, including scarring alopecia, bullous dermatoses or cysts, and comedones. In atypical presentations, histopathology is essential for the diagnosis. We present two cases of MF with clinical urticarial lesions and a striking blood involvement that responded to mogamulizumab treatment. Histopathologically, both cases had classic MF features and shared a peculiar immunophenotype, with positivity for CD25 and FOXP3. Differential diagnoses included urticarial lymphomatoid drug reactions and other lymphomas, like T-cell prolymphocytic leukemia, atypical Sézary syndrome, or adult T-cell lymphocytic leukemia. A low suspicion threshold is necessary for the diagnosis of atypical presentations of MF.
Assuntos
Imunofenotipagem , Micose Fungoide , Neoplasias Cutâneas , Humanos , Micose Fungoide/patologia , Micose Fungoide/diagnóstico , Neoplasias Cutâneas/patologia , Masculino , Imunofenotipagem/métodos , Diagnóstico Diferencial , Pessoa de Meia-Idade , Feminino , Urticária/patologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Idoso , Fatores de Transcrição ForkheadRESUMO
BACKGROUND: Mycosis fungoides is rarely associated to B-cell malignancies, and the few reported cases are mainly internal lymphomas involving secondarily the skin (ie, chronic lymphocytic leukemia). OBJECTIVES: The aim of our study is to describe the clinical and histopathological features of 4 patients presenting with 2 concurrent primary cutaneous lymphomas and review the pertinent literature. METHODS: We identified 4 cases of concurrent primary cutaneous lymphomas in our institutions. An extracutaneous lymphoma was ruled out on the basis of a complete work out. We performed a PubMed search to identify reported cases of primary cutaneous composite or concurrent lymphomas. RESULTS: Eleven cases of primary cutaneous concurrent lymphomas have been described in the literature. Counting all together (our cases and the cases previously described in the literature), mycosis fungoides was the most frequent primary cutaneous T-cell lymphoma (TCL) (13/15), followed by 1 case of peripheral TCL-NOS and 1 case of subcutaneous panniculitis-like TCL. Regarding the associated primary cutaneous B-cell lymphomas, 8/15 cases consisted of low-grade B-cell lymphomas [that is, 5 marginal zone lymphoma (in the most recent classification reclassified as marginal zone lymphoproliferative disorder, MZLD, 2 follicular-center B-cell lymphoma (primary cutaneous follicle-center lymphoma) and 1 low-grade NOS B-cell lymphoma]; 4/15 were associated to Epstein-Barr virus; 1 case consisted of a methotrexate-associated lymphoproliferative disease, and 2 cases consisted of primary cutaneous diffuse large B-cell lymphoma-leg type. CONCLUSIONS: Primary cutaneous concurrent lymphomas are exceptional. Clinicopathological correlation and a complete workout to reach the correct diagnosis may guide the appropriate treatment in each case.
Assuntos
Infecções por Vírus Epstein-Barr , Linfoma de Zona Marginal Tipo Células B , Linfoma Cutâneo de Células T , Micose Fungoide , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Herpesvirus Humano 4 , Micose Fungoide/patologia , Linfoma Cutâneo de Células T/patologiaRESUMO
Anaplastic large cell lymphoma (ALCL) with leukaemic presentation (either ab initio or along the course of the disease) has been rarely reported. Irrespective of ALK expression in the neoplastic cells, it features a dismal prognosis. We report a rare case of leukaemic, small cell variant ALK-positive ALCL with 9-year survival in a young woman who was treated upfront with corticosteroids and standard chemotherapy, and review thoroughly the previously published cases. Such an unexpected, good outcome hints at the existence of different clinical subgroups in the leukaemic variant of ALK-positive ALCL.
Assuntos
Linfoma Anaplásico de Células Grandes , Feminino , Humanos , Linfoma Anaplásico de Células Grandes/diagnóstico , Linfoma Anaplásico de Células Grandes/tratamento farmacológico , Linfoma Anaplásico de Células Grandes/metabolismo , Quinase do Linfoma Anaplásico , Receptores Proteína Tirosina Quinases/uso terapêutico , PrognósticoRESUMO
ABSTRACT: We report a case of mycosis fungoides (MF) in an 18-year-old man whose neoplastic T cells expressed CD4, CD8, and CD56, with no evidence of TCR-delta or Epstein-Barr virus (EBER) expression. Clinically, neither hypopigmentation nor hyperpigmentation nor poikilodermatous skin lesions were present, and the lesions subsided with oral corticoids and retinoids and environmental solar ultraviolet exposure. Our case represents the oldest patient reported so far with nonpoikilodermatous, CD8/CD56 MF and adds to the phenotypic diversity of MF in the pediatric population. This distinct phenotype does not seem to be linked to a more aggressive course than the classic CD-4 positive one.
Assuntos
Infecções por Vírus Epstein-Barr , Micose Fungoide , Neoplasias Cutâneas , Criança , Humanos , Herpesvirus Humano 4 , Micose Fungoide/patologia , Neoplasias Cutâneas/patologia , Linfócitos T CD8-Positivos/patologiaRESUMO
ABSTRACT: Skin manifestations in the context of underlying hematological malignancies are well known and not an infrequent clinical finding. They can represent specific neoplastic infiltrates or be considered as reactive. In the latter group, where granulomatous dermatitis is included, controversy has emerged recently. According to newly reported data, the histiocytes comprising these granulomata can carry the same molecular alterations found in the primary process. Moreover, the skin manifestations in these patients are sometimes the initial clue for the diagnosis of the underlying malignancy. We present here 2 cases with granulomatous skin infiltrates preceding the diagnosis of myelodysplastic/myeloproliferative neoplasms. In one of them, the same IDH2 mutation was detected in granulomatous lesions on the skin and in the bone marrow. This was performed by pyrosequencing instead of next-generation sequencing, with improved cost-effectiveness.
Assuntos
Doenças Autoimunes , Dermatite , Neoplasias , Doenças Autoimunes/patologia , Medula Óssea/patologia , Dermatite/patologia , Granuloma/patologia , Humanos , Neoplasias/patologia , Pele/patologiaRESUMO
Spontaneous remissions (SRs) in acute myeloid leukemia (AML) are infrequent, poorly documented and transient. Similarly, morphological and cytogenetic complete remissions (CR) under azacitidine treatment are scarce. We report a 71-year-old man with a secondary AML arising from essential thrombocythemia (ET), who developed an SR after discontinuation of azacitidine following a respiratory infection (four courses were administered). The distinctive feature of our case is the depth of the achieved CR, documented by next-generation sequencing (NGS) techniques. We also detected persistence of molecular lesions that might already have been present in the previous ET clone. Our patient relapsed 5 months after achieving CR. We conclude that our patient showed a spontaneous remission of his AML rather than an exquisite response to azacitidine. We hypothesize that the concurrent respiratory infection, or any other unknown trigger, might have activated his immune system forcing the leukemic stem cell to enter a quiescent state through a yet unexplained mechanism.
Assuntos
Leucemia Mieloide Aguda , Trombocitemia Essencial , Idoso , Azacitidina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Indução de Remissão , Remissão EspontâneaRESUMO
We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7·9 and 15·8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0·001). Complete response (CR) to treatment was associated with better PFS (62·6 vs. 4 months; P < 0·001) and longer OS (67·0 vs. 7·3 months; P < 0·001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and -negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological sub-classification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.
Assuntos
Linfoma de Células T Periférico/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Antígeno Ki-1/análise , Linfoma de Células T Periférico/diagnóstico , Linfoma de Células T Periférico/epidemiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Espanha/epidemiologia , Análise de Sobrevida , Adulto JovemRESUMO
Acral lymphomatoid papulosis (a-LyP) is a rare clinical variant of LyP whose diagnosis may be challenging. A case series of a-LyP was studied clinically, histopathologically, immunohistochemically, and from molecular point of view. Including ours, 25 cases of a-LyP have so far been reported. Clinically, a-LyP may present as acral involvement exclusively, in combination with mucosal lesions, (in itself a rare presentation), or in association with conventional LyP. The age of presentation was slightly higher than that of conventional LyP (55 vs 45 years) and a male predominance has been observed, as usually reported. Histopathologically, no morphological differences exclusively from conventional LyP were observed. LyP types A and E were the main variants. We describe for the first time one case of type D a-LyP. Acral LyP is a rare entity and correct diagnosis can only be reached with clinical and histopathological correlation, to avoid aggressive treatment of this indolent lymphoproliferative disorder.
Assuntos
Antígeno Ki-1/metabolismo , Papulose Linfomatoide/patologia , Transtornos Linfoproliferativos/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica/métodos , Papulose Linfomatoide/diagnóstico , Papulose Linfomatoide/metabolismo , Transtornos Linfoproliferativos/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
ABSTRACT: Primary cutaneous acral CD8-positive T-cell lymphoma consists of slow-growing nodules in acral sites with a histopathology, suggesting high-grade lymphoma despite the indolent clinical course. It has been recently included in WHO-EORTC classification for primary cutaneous lymphomas as a provisional entity. A correct diagnosis of this entity is important because its differential diagnosis include more aggressive cutaneous lymphomas. We present a 53-year-old woman with an indolent solitary nodule on her right leg, which histopathologically showed features of CD8-positive T-cell lymphoma, although with some peculiarities, including epidermotropism, absence of CD68 expression, and positivity for GATA3 and Bcl6 in neoplastic cells. This case could contribute to better define the spectrum of this rare cutaneous lymphoma.
Assuntos
Biomarcadores Tumorais/análise , Linfócitos T CD8-Positivos/química , Fator de Transcrição GATA3/análise , Linfócitos do Interstício Tumoral/química , Linfoma Cutâneo de Células T/química , Proteínas Proto-Oncogênicas c-bcl-6/análise , Neoplasias Cutâneas/química , Biópsia , Linfócitos T CD8-Positivos/imunologia , Feminino , Humanos , Imuno-Histoquímica , Linfócitos do Interstício Tumoral/imunologia , Linfoma Cutâneo de Células T/imunologia , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/cirurgia , Pessoa de Meia-Idade , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do TratamentoRESUMO
The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.
Assuntos
Infecções por Coronavirus/patologia , Histiócitos/patologia , Linfo-Histiocitose Hemofagocítica/patologia , Linfo-Histiocitose Hemofagocítica/virologia , Pneumonia Viral/patologia , Síndrome do Desconforto Respiratório/patologia , Síndrome do Desconforto Respiratório/virologia , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus , Medula Óssea/patologia , COVID-19 , Feminino , Humanos , Hiperplasia/patologia , Hiperplasia/virologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2RESUMO
AIMS: To present four examples of clonally related Epstein-Barr virus (EBV)-associated large-cell transformation of marginal zone lymphoma (MZL) (of nodal, extranodal and splenic types), occurring 120, 11 and 5 months after the initial diagnosis in three instances, and concurrently in one case; and to discuss several interesting features of EBV infection. METHODS AND RESULTS: Somatic mutations were detected by use of a customised panel for next-generation sequencing and polymerase chain reaction studies of IgH in both low-grade and high-grade components of each case. In case 1, the initial biopsy of nodal MZL showed scattered EBV-positive cells, which might constitute an indication of EBV-induced progression. Case 2 showed heterogeneous EBV expression, a phenomenon attributable to loss of the EBV episomes during cell division, or to a secondary superinfection or reactivation of the virus. In case 3, p53 overexpression related to gene mutation and EBV-encoded small RNAs were identified in the same neoplastic component. In case 4, the mucosa-associated lymphoid tissue-type MZL and the high-grade component were identified concurrently in a patient previously treated with methotrexate for an autoimmune disorder. CONCLUSION: These data suggest that the presence of EBV should be added to the list of potential markers to be analysed for MZL prognosis.
Assuntos
Transformação Celular Neoplásica/patologia , Infecções por Vírus Epstein-Barr/complicações , Linfoma de Zona Marginal Tipo Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/virologia , Idoso , Feminino , Herpesvirus Humano 4 , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Hepatosplenic T-cell lymphoma (HSTL) is an uncommon, aggressive peripheral T-cell lymphoma with a dismal prognosis, usually expressing gamma-delta T-cell receptor on immunohistochemical study. We report the second instance in the literature of a solitary skin nodule heralding recurrence of HSTL. The patient was a 40-year-old man in apparent remission from HSTL, 4 years after chemotherapy and autologous bone marrow transplant. Biopsy of a flank lesion showed atypical lymphoid cells involving the dermis with a perivascular and periadnexal pattern, and fat lobules of the subcutaneous tissue. Their phenotype mirrored that of previous biopsies, with expression of CD2, CD3, CD7, CD56, and T-cell receptor-gamma, and lack of T-cell receptor-beta, CD4, CD5, and CD8. Cutaneous involvement by HSTL has rarely been reported either at initial diagnosis or at recurrence, and represents a diagnostic pitfall for primary cutaneous gamma-delta T-cell lymphoma.
Assuntos
Neoplasias Hepáticas/patologia , Linfoma de Células T Periférico/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias Cutâneas/patologia , Neoplasias Esplênicas/patologia , Adulto , Humanos , Linfoma de Células T Periférico/imunologia , Masculino , Receptores de Antígenos de Linfócitos T gama-deltaRESUMO
We report on a 74-year-old man with a cutaneous B-cell follicle center lymphoma, which was treated upfront with systemic rituximab and suffered several local relapses. The first of the local recurrences, 10 months after completion of treatment, was characterized by a dense T-cell infiltrate that obscured a minor population of B-cell lymphoma cells, suggesting a second primary cutaneous T-cell lymphoma. This represents a previously not reported diagnostic pitfall and underscores the importance of performing sequential biopsies when dealing with lymphoma recurrences in this setting.
Assuntos
Linfoma de Células B/diagnóstico , Linfoma Folicular/diagnóstico , Recidiva Local de Neoplasia/diagnóstico , Neoplasias Cutâneas/diagnóstico , Linfócitos T/patologia , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/patologia , Masculino , Recidiva Local de Neoplasia/patologia , Rituximab/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
Cutaneous eruption of lymphocyte recovery (ELR) during bone marrow (BM) aplasia recovery after intensive chemotherapy has been reported in very few patients. The presence of skin rashes in patients with acute leukemia who are undergoing intensive chemotherapy and BM transplantation is a diagnostic challenge because of the clinical similarity between drug eruptions, infiltrates related to the relapse of the underlying disease, cutaneous graft-versus-host disease, and ELR. IDH1 mutations have been identified as a recurrent genetic anomaly in acute myeloid leukemia and myelodysplastic syndromes. However, until now, this IDH1 mutation has not been reported as being shared by myeloid cells and non-neoplastic inflammatory cells in this clinical setting. Here, we present the rare case of a woman diagnosed with myelodysplastic syndrome that evolved into an acute myelogenous leukemia with leukemic cutaneous infiltrate. The patient developed ELR after the intensive chemotherapy administered before BM transplantation. The IDH1 mutation was identified in BM cells and in myeloid and inflammatory cells in skin biopsies before allogeneic BM transplantation. We discuss the main aspects of the differential diagnosis of these cutaneous reactions in leukemic patients and the biological significance of the IDH1 mutation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Toxidermias/patologia , Isocitrato Desidrogenase/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Idoso , Citarabina/efeitos adversos , Feminino , Humanos , Idarubicina/efeitos adversos , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologiaAssuntos
Fenótipo , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/imunologia , Masculino , Linfoma de Células T Periférico/genética , Linfoma de Células T Periférico/patologia , Linfoma de Células T Periférico/imunologia , Feminino , Pessoa de Meia-Idade , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/patologia , Transtornos Linfoproliferativos/imunologia , Idoso , Linfócitos T CD4-Positivos/imunologia , Mutação , Adulto , Células T Auxiliares Foliculares/imunologia , Diagnóstico Diferencial , Análise Mutacional de DNA , Linfoma Cutâneo de Células T/genética , Linfoma Cutâneo de Células T/patologia , Linfoma Cutâneo de Células T/imunologiaRESUMO
Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) is a diagnosis of exclusion, showing extreme cytological and phenotypic heterogeneity. Skin involvement of PTCL may be primary or secondary. Diagnosis of histiocytosis may be difficult, requiring clinical-pathological correlation. We describe a laryngeal atypical histiocytic lesion (AHL) and a nasal PTCL, NOS with cutaneous involvement in the same patient presenting with peculiar histopathologic and immunophenotypic features. The laryngeal neoplasm showed morphological and immunophenotypic evidence of histiocytic differentiation and does not fit any other category of the WHO classification nor the revised classification of histiocytosis. The nasal and cutaneous lesions presented features close to natural killer/T-cell lymphoma and gamma-delta T-cell lymphoma but did not meet accurately the WHO criteria. A somatic activating Q61K mutation was found on exon 3 of the NRAS gene in both AHL and PTCL, NOS. The mutation on NRAS gene in both AHL and PTCL, NOS may suggest a common origin from a precursor cell.