Vemurafenib-induced histiocytoid neutrophilic panniculitis simulating myeloid leukaemia cutis

Neutrophilic panniculitis is an infrequent but characteristic adverse event under therapy with BRAF inhibitors (BRAFi). Since the approval of vemurafenib for treatment of metastatic melanoma in 2011, only two cases of neutrophilic panniculitis in malignancies other than melanoma have been published. Histiocytoid infiltrates of immature neutrophils resembling histiocytes or myelocytes have been reported in Sweet’s syndrome and rarely in other neutrophilic dermatoses. We describe a novel variant of neutrophilic panniculitis with histiocytoid myeloid cells in an early lesion from a patient treated with vemurafenib in combination with an anti-EGFR (epidermal growth factor receptor) agent for metastatic colon carcinoma, three weeks after initiation of therapy. Recognizing this variant of panniculitis associated to BRAFi can avoid misinterpretation of the atypical subcutaneous infiltrate as myeloid leukaemia cutis.     

Vemurafenib-induced progression of breast cancer: a case report and review of the literature

Vemurafenib, a specific inhibitor of mutated BRAF kinase, may activate wild-type BRAF and therefore induce squamous cell skin carcinomas in patients treated for melanoma. All vemurafenib clinical trials excluded patients with multiple primary malignant tumors; therefore, the action of this drug on concurrent BRAF wild-type malignancies remains insufficiently studied. We observed a patient, who was administered vemurafenib for BRAF mutation-containing melanoma, but experienced immediate relapse of previously controlled breast cancer disease. Interestingly, breast cancer lesions underwent regression soon after vemurafenib discontinuation. Therefore, caution must be taken while considering vemurafenib treatment for patients with multiple tumors.     

Subcutaneous panniculitis lymphoma: erythema nodosum-like

We report the case of a patient who presented with painful nodular subcutaneous lesions on the lower limbs and episodes of high temperature (> 39.5 degrees C). Histologic examination and immunohistochemical study of a biopsy specimen from a nodular lesion were consistent with the diagnosis of subcutaneous panniculitis-like T-cell lymphoma, a rare form of non-Hodgkin lymphoma. Diagnosis is made particularly difficult, especially in the early stages, by nonspecific clinical features shared by many types of panniculitis. Therefore, it seems advisable to consider the possibility of this type of lymphoma in all cases of panniculitis and to perform careful and continuous follow-up of all cases in which a clear diagnosis is not formulated at the outset, with regular repetition of skin biopsies at appropriate intervals.     

Cytophagic histiocytic panniculitis: a diagnostic dilemma.

Cytophagic histiocytic panniculitis (CHP) is a recently recognized entity that frequently poses a perplexing diagnostic problem. Although the classical case presents with a relapsing fever, subcutaneous nodules, pancytopenia and liver dysfunction, most patients have in addition a multitude of other manifestations which confuse the clinical picture. Notwithstanding the variable clinical course, the disease frequently terminates in fatal hemorrhage. Diagnosis is based on histological features. A lobular panniculitis with an infiltrate of cytologically benign cytophagocytic histiocytes in skin nodules is the sine qua non of CHP. Hence, a deep skin biopsy which includes subcutaneous fat is mandatory to establish the diagnosis. Published information regarding this newly described entity remains scarce and we report two cases of CHP, one occurring in a 30-year-old Kadazan man and another in a 17-year-old Chinese woman seen at the University Hospital, Kuala Lumpur. The latter case presented with exudative ascites, an unusual feature, possibly due to intra-abdominal panniculitis. In addition, we record the development of cirrhosis in the same patient.     

Chronic neutrophilic leukemia with acute myeloblastic transformation

We report a rare case of chronic neutrophilic leukemia (CNL) which terminated in acute myeloblastic transformation 3 years after the onset of the disease. The increased leukocytes were mainly neutrophils at various maturational stages until 1 month before transformation without dysplastic hematopoietic cells or other myeloproliferative disorders. Repeated analyses for the Philadelphia chromosome (Ph1), rearrangement of the BCR gene or chimeric BCR/ABL mRNA, major, minor and mu, were negative. Genomic analysis of granulocyte colony-stimulating factor (G-CSF) receptor did not reveal any abnormality. The clinical manifestations were characterized by hyperleukocyte syndrome with respiratory distress and ischemic legs with gangrene.     

Coexistence of chronic neutrophilic leukemia with multiple myeloma

A case report of simultaneous presentation of chronic neutrophilic leukemia and multiple myeloma (IgG kappa) in a 71-year-old male is described. The patient showed mature neutrophilic leukocytosis, hepatosplenomegaly, high neutrophil alkaline phosphatase score, hyperuricemia, neutrophils with toxic granulation and D?hle bodies, absence of Philadelphia chromosome and of the bcr-abl fusion gene. Moreover, a monoclonal IgG kappa paraproteinemia (36.93 g l(-1)) was detected. Bence-Jones proteinuria was 3.84 g l(-1). The bone marrow was grossly hypercellular with marked myeloid hyperplasia and aggregates of plasma cells. The patient died of severe bronchopneumonia after the transformation of chronic neutrophilic leukemia to acute myelomonocytic leukemia, 1.5 years following diagnosis.     

Cytophagic histiocytic panniculitis. A variant of malignant histiocytosis

This report describes a patient with cytophagic histiocytic panniculitis in which the aggressive use of chemotherapeutic agents resulted in an apparent remission. The histiocytic nature of the process was confirmed by immunohistochemical techniques. There are many similarities with malignant histiocytosis, and it is believed that this entity should be regarded as a variant of malignant histiocytosis.     

Influence of irradiation on neutrophilic granulocyte function.

BACKGROUND: Neoadjuvant radiotherapy is a common treatment modality for patients with Stage II and III rectal carcinoma but, after surgery, often is complicated by local infections. To define a possible influence of radiotherapy on neutrophilic granulocytes in the neighborhood of tumor cells, the authors investigated their function in vitro. METHODS: Density gradient-purified granulocytes from healthy donors were used for all tests. These cells were cocultured with the colon carcinoma cell line HRT-18 and irradiated. Their function was assessed by measuring luminol-enhanced chemiluminescence and migration against the chemoattractant formyl-methionyl-leucine-phenylalanine. RESULTS: Although irradiation decreased, the addition of tumor cells increased reactive-oxygen species release in granulocytes, which was enhanced further by phorbol myristate acid (PMA), even after several hours. All contacts with tumor cells, however, caused immediate radical release that was inversely proportional to the radiation dose. Na?ve and irradiated cells were stimulated further by PMA. Migration of granulocytes clearly was inhibited by tumor cells and irradiation, whereas the depth of invasion was enhanced by higher doses of radiation. CONCLUSIONS: The current data show clearly that the influence of radiotherapy on local defense against colorectal carcinoma is limited and cannot explain the increased rate of infectious complications.     

Transition of polycythemia vera to chronic neutrophilic leukemia

Two cases of polycythemia vera (PV) had transition to a hematological condition compatible with chronic neutrophilic leukemia (CNL) 17 and 8 years after diagnosis, respectively. One patient was treated with carboquone followed by hydroxyurea (HU) and the other with HU during PV phase. On transition, both had neutrophilia with white blood cell count above 40,000/microl, elevated neutrophil alkaline phosphatase activity, splenomegaly, normal karyotype without bcr-abl rearrangement. Busulfan was temporally effective in controlling the neutrophil count. However, one patient progressed to the so-called spent phase and the other subsequently had multiple transitions between PV and CNL. These cases may represent a form of uncommon evolution of PV and support the contention that CNL is a type of myeloproliferative disorder and that at least some CNL cases have derangement at the hematopoietic stem cell level.     

Mesenteric panniculitis versus pancreatitis: A computed tomography diagnostic dilemma

A case of mesenteric panniculitis is described in a patient with CT features mimicking pancreatitis. Emphasis is on the important CT features for accurate diagnosis.     

Arachidonic acid metabolism in the neutrophilic granulocytes in lymphogranulomatosis

Metabolism of arachidonic acid in neutrophils was studied in vitro in blood samples obtained from 36 patients with Hodgkin's disease of various stage and histology and 32 healthy donors. The basic metabolites were: leucotriene B4, such products of its omega-oxidation as 20-hydroxy-leucotriene B4 (20-OH-LTB4) and 20-carboxy-leucotriene B4 (20-COOH-LTB4), and 5-hydroxyeicosatetraenic acid. Their profile proved identical in patients with Hodgkin's disease and healthy donors. Most patients with Hodgkin's disease showed a decrease in leucotriene B4 and 5-hydroxyeicosatetraenic acid and an increase in the level of omega oxidation of leucotriene B4 as assessed by omega catabolite/leucotriene B4 ratio. The levels of 5-hydroxyeicosatetraenic acid and leucotriene B4 omega-oxidation were found to depend upon histology and stage of Hodgkin's disease. They were nearly normal in patients with stage III, mixed cellular disease, B-symptoms and signs of biologic activity of tumor. A direct correlation was established between the level of leucotriene B4 omega oxidation in neutrophils and that of ceruloplasmin in blood serum of patients with various stages of Hodgkin's disease.     

Carcinoma of the pancreas with neuroendocrine differentiation and nodular panniculitis

BACKGROUND: On rare occasions tumours of the pancreas produce high amounts of pancreatic lipase. The enzyme activity in the blood and in different tissues causes a syndrome called nodular panniculitis by focal necrosis of lipids and a concomittant inflammatory reaction. CASE REPORT: A 72-year-old man was admitted to the dermatology clinic with the diagnosis of erythema nodosum. The patient had been well until 3 months earlier when painful red nodes developed on the skin of both shanks. He complained of profuse night sweating and a weight loss of 10 kg within that time but did not have fever. He also had noticed a painful swelling of his right index finger, left middle finger and the third toe on his left foot. Biopsy of the nodes revealed a focal necrosis of fatty tissue. Laboratory examinations showed a highly elevated concentration of serum pancreatic lipase. Further investigations showed a tumour in the pancreas and several osteolytic lesions. Tumour biopsy revealed a neuroendocrine carcinoma. After tumour resection serum lipase level immediately fell to almost normal values, and all skin and bone manifestations disappeared quickly. CONCLUSION: Due to its clinical appearance the panniculitis syndrome is most often mistaken for either erythema nodosum or rheumatoid arthritis. A resection of the tumour after correct diagnosis should always be considered because the widespread manifestations in the skin and bones do not represent distant metastasis and have a very good chance to dissolve completely.     

慢性中性粒细胞白血病预后因素的研究进展

慢性中性粒细胞白血病（chronic neutrophilic leukemia,CNL）是一种少见类型的骨髓增殖性肿瘤。集落刺激因子3受体（colony-stimulating factor 3 receptor,CSF3R）突变为特征性分子学标志。目前,CNL的治疗尚无统一标准,靶向药物芦可替尼（ruxolitinib）等可改善部分患者的生存,异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo- HSCT）仍然是唯一可能治愈的方法。随着CNL基因组学研究的不断深入,许多因素被证明与预后相关。本文综述了影响CNL患者预后的临床因素、细胞分子遗传学等因素,以期构建更为完善的预后评估系统,更好地指导患者的治疗。      

Chronic neutrophilic leukemia and myeloma. Report on long survival

A case of chronic neutrophilic leukemia associated with multiple myeloma is described. The patient appears to be the longest surviving case reported in the literature. Since myeloma developed several years after leukemia, the possible precancerous role of myeloproliferative syndromes is proposed.     

Generalized neutrophilic dermatosis: a rare presentation of myelodysplastic syndrome

We present a 30-year-old man admitted with generalized cutaneous lesions, fever and cough. Examination of skin biopsies of a papular lesion revealed dense neutrophilic infiltration of the upper dermis, so these lesions were diagnosed as neutrophilic dermatosis. Peripheral blood examination and bone marrow findings confirmed the diagnosis of myelodysplastic syndrome with excess blasts. The cutaneous lesions improved after administration of corticosteroid and follow-up bone marrow examination revealed a normocellular marrow. One year later he referred with acute myelogenous leukemia (AML-M0). Unfortunately, he did not respond to treatment and died a few months later due to disease progression.     

慢性中性粒细胞白血病2例并文献复习

目的:研究对慢性中性粒细胞白血病(CNL)的特点.方法:报告2例CNL并结合文献进行复习.结果:患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2.5年后转化为急性白血病.结论:CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的.     

慢性中性粒细胞白血病2例并文献复习

目的：研究对慢性中性粒细胞白血病（CNL）的特点。方法：报告2例CNL并结合文献进行复习。结果;患者中性粒细胞明显增多,脾大,中性粒细胞碱性磷酸酶积分增高,无Ph染色体、bcr-abl融合基因,骨髓粒系增生,无病态造血和明显纤维化依据,排除了如类白血病反应、其他克隆性血液病引起的中性粒细胞增多,其中1例伴有单克隆免疫球蛋白血症,2．5年后转化为急性白血病。结论;CNL是一种少见的骨髓增殖性疾病,多发生于老年人,预后差,治疗无标准方案,年轻患者应进行异基因造血干细胞移植以达到治愈目的。