No abstract

Interferon-alpha therapy has been shown to be active in the treatment of mycosis fungoides although the individual response to this therapy is unpredictable and dependent on essentially unknown factors. In an effort to better understand the molecular mechanisms of interferon-alpha resistance we have developed an interferon-alpha resistant variant from a sensitive cutaneous T-cell lymphoma cell line. We have performed expression analysis to detect genes differentially expressed between both variants using a cDNA microarray including 6386 cancer-implicated genes. The experiments showed that resistance to interferon-alpha is consistently associated with changes in the expression of a set of 39 genes, involved in signal transduction, apoptosis, transcription regulation, and cell growth. Additional studies performed confirm that STAT1 and STAT3 expression and interferon-alpha induction and activation are not altered between both variants. The gene MAL, highly overexpressed by resistant cells, was also found to be expressed by tumoral cells in a series of cutaneous T-cell lymphoma patients treated with interferon-alpha and/or photochemotherapy. MAL expression was associated with longer time to complete remission. Time-course experiments of the sensitive and resistant cells showed a differential expression of a subset of genes involved in interferon-response (1 to 4 hours), cell growth and apoptosis (24 to 48 hours.), and signal transduction.

PGA is different to GA not only histologically but also clinically. It is a disseminated disease, affecting both children and adults, which is characterized by the presence of multiple papules, most of them umbilicated and/or crusted, and characteristically pustular lesions and scars. Histology suggests that the superficial localization of the necrobiotic granuloma leads to the epidermal perforation. Treatment is disappointing.

Objective: To describe a series of 41 patients with fresh lesions of Sweet syndrome in which the histopathologic study demonstrated an inflammatory infiltrate mostly composed of histiocytoid mononuclear cells. Design: Histopathologic, immunohistochemical, and cytogenetic studies of the inflammatory infiltrate in a case series of histiocytoid Sweet syndrome. Setting: University departments of dermatology and a private laboratory of dermatopathology. Methods: Conventional histopathologic study as well as immunohistochemical investigations were performed using the alkaline phosphatase antialkaline phosphatase technique with a large panel of antibodies. In some cases, fluorescent in situ hybridization studies were performed to investigate the presence of the bcr/abl gene fusion. Results: Immunohistochemical studies demonstrated that most cells of the infiltrate showed immunoreactivity for CD15, CD43, CD45, CD68, MAC-386, HAM56, and ly-sozyme, which is consistent with a monocytichistiocytic immunoprofile. However, intense myeloperoxidase reactivity was detected in most of the cells with histiocytic appearance, which raised the possibility of specific cutaneous involvement by myelogenous leukemia. Nevertheless, cytologic peripheral blood examinations, fluorescent in situ hybridization studies to investigate the bcr/abl gene fusion, and follow-up of the patients, taken all together, ruled out this possibility. Conclusions: This case series demonstrates that some fresh cutaneous lesions of Sweet syndrome are histopathologically characterized by an infiltrate mostly composed of cells that may be misinterpreted as histiocytes, when in fact they are immature myeloid cells. We named this histopathologic variant histiocytoid Sweet syndrome, which should not be mistaken with leukemia cutis or other inflammatory dermatoses that are histopathologically characterized by histiocytes interstitially arranged between collagen bundles of the dermis.

Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.