Defects in the NF1 gene have been implicated in the inherited disorder neurofibromatosis type 1, which is characterized by several developmental abnormalities including an increased frequency of benign and malignant tumours of neural crest origin (neurofibromas and neurofibrosarcomas respectively). The NF1 gene encodes a ubiquitous protein homologous to p120GAP, the GTPase-activating protein (GAP) for the products of the ras protooncogenes. When expressed in non-mammalian systems, the region of the NF1 gene homologous to p120GAP produces a protein with GAP-like activity. Here we present evidence that the ras proteins in malignant tumour cell lines from patients with type 1 neurofibromatosis are in a constitutively activated state, as judged by the guanine nucleotide bound to them, and are necessary for cellular proliferation. These cells contain p21ras and p120GAP that are both functionally wild type, but barely any functional NF1 protein. Our results show that the NF1 protein is normally essential for correct negative regulation of ras proteins in the cell, even in the presence of normal p120GAP, and they support the hypothesis that NF1 is a tumour-suppressor gene whose product acts upstream of ras.

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Summary Sweet syndrome (SS) is an acute febrile neutrophilic dermatosis. It has been associated with malignant disease, especially acute myeloid leukaemia (AML), infections, autoimmune disorders and drugs, particularly granulocyte colony‐stimulating factor (GCSF). No cause is found in the rest, which are labelled idiopathic. We describe 15 patients with SS, which we believe represent ‘immune dysregulation’ secondary to myelodysplastic syndrome (MDS). We initially identified 31 patients with SS in a cohort of 744 patients with MDS and 215 with AML seen over a 6‐year period (2004–10). The cause in 16 patients could be attributed either to administration of GCSF or chemotherapy. The eruption was brief and resolved spontaneously or following withdrawal of GCSF. Fifteen patients however, had a chronic debilitating illness dominated by the skin eruptions. Diagnosis of chronic relapsing SS was delayed because the pathology was not always typical of classical neutrophil‐rich SS and included lymphocytic and histiocytoid infiltrates and bone marrow was not always performed because the relevance of the eruption to MDS was often not immediately appreciated. All these patients had ‘low risk’ MDS, diagnosed at a median of 17 months (range 0–157) following the diagnosis of SS. We describe a chronic debilitating episodic clinically distinctive skin eruption with features of SS but not always definitive histopathology often associated with immunological abnormalities affecting other systems related to underlying low risk MDS.

Malignant eccrine spiradenoma is a rare skin tumor of sweat gland origin. We present the first reported case of this tumor in the female genitalia. Due to the rarity of this tumor, there has yet to be an established standard of care. The present case is that of a 41-year-old woman with malignant eccrine spiradenoma of the periclitoral region. She had an 18-month history of a recurrent, painful mass adjacent to the clitoris. Her diagnosis was made after excision of the cystic tumor. The patient then underwent a partial radical vulvectomy with bilateral sentinel lymph node sampling. As malignant eccrine spiradenoma is a rare tumor, no standard care exists for treatment and postoperative management. Based on our review of the literature, wide local excision appears to be the preferred initial treatment. Furthermore, adjuvant chemotherapy and/or radiation does not seem to improve survival in patients with advanced or recurrent cancer. Although lymph node sampling and/or lymphadenectomy is frequently reported in the treatment of this tumor, hematogenous metastasis can also occur. Therefore, these patients require close postoperative follow-up for recurrent disease.

DiagnosisCT, PET/CT and MRI brain: Stage IVB (T2b N3 M1) NSCLC EBUS: TTF1-positive adenocarcinoma ALK/ROS1 IHC negative, PD-L1 IHC negative, EGFR wild type (COBAS v2) ctDNA (Guardant 360) NGS reported: TP53 T125T mutation Tissue sample sent for orthogonal NGS (FoundationOne) Commenced carboplatin and pemetrexed chemotherapy Notified that there was insufficient tissue for orthogonal genotyping Repeat EBUS for molecular analysis Pembrolizumab added to cycles 3 and 4 of carboplatin and pemetrexed CT response evaluation following cycle 4: Partial response Tissue NGS report: EGFR exon 20 insertion (A763_Y764insFQEA)

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This pilot data support the usefulness of these composite biomarker panels in the prediction of severity and diagnosis of aGVHD in patients undergoing T-cell-depleted reduced intensity allogeneic HSCT.

Intractable pruritus without visible primary skin lesions and refractory to antihistamines as a primary presentation of chronic myelomonocytic leukaemia (CMML) and myelodysplastic syndrome (MDS) is not well recognised. We present two cases of CMML and two cases of MDS with this challenging symptom. In two of them, the pruritus preceded the diagnosis of MDS/CMML by months. Various chemotherapeutic and immunosuppressive options were used with variable success. In one of the cases, the pruritus persisted despite achieving morphological remission of CMML with azacitidine but had a remarkable complete response to cladribine. The pathogenesis of intractable itching in CMML and MDS remains unclear but seems to be linked to the biology of these diseases and could precede definitive diagnostic features. Earlier diagnosis of these myeloid disorders may therefore be aided by increasing awareness among clinicians of the association with pruritus.