Leukemia Cutis Research Articles

Chronic lymphocytic leukemia and the skin: implications for the dermatologist.

B-cell chronic lymphocytic leukemia (CLL) is the most prevalent leukemia in the United States, and its diagnosis can have many dermatologic implications. For one, the cutaneous manifestations of CLL include several entities, most notably leukemia cutis, eosinophilic dermatosis of hematologic malignancy, and a heightened risk of skin infections. Additionally, CLL patients are at an increased risk of secondary malignancies, most commonly of the skin. Furthermore, a number of commonly utilized treatments for CLL have cutaneous implications which should be considered in the interdisciplinary management of CLL patients. In this review, we will provide an update on the diverse cutaneous manifestations of CLL and CLL-directed therapies in order to help guide dermatologic management of this increasingly prevalent patient population.

CHRONIC LYMPHOBLASTIC LEUKEMIA DIAGNOSED BY PRIMARY CUTANEOUS LESION

Chronic lymphocytic leukemia (CLL) is a malignant, low-grade, monoclonal disorder characterized by the accumulation of lymphocytes with variable clinical features. Cutaneous manifestations or leukemia cutis are non-specific, uncommon presentations of CLL and can present in many different ways. In this case report, we discuss a 76-year-old male who presented with skin lesions of the lower limbs and severe itching. Due to the lack of response to the treatment with topical corticosteroids, initial tests were carried out. Complete blood count results indicated lymphocytosis. Eventually Ultimately, the skin lesions led to the diagnosis of CLL. The patient was treated with bendamustine-rituximab (BR). After receiving the treatment, all cutaneous manifestations and generalized itching disappeared. This case highlights the importance of comparing similar cases of CLL presented with dermatological conditions in order to to understand proper management and practice.

Pediatric Leukemia Cutis: Darier’s Sign

Leukemia Cutis (LC) is defined as infiltration and proliferation of neoplastic cells of lymphoid or myeloid lineage in the epidermis, dermis or hipodermis. The case of a 7-month-old infant with Leukemia Cutis, characterized by papules, nodules with a positive Darier’s sign, with histopathological findings of an infiltrate of monomorphic lymphoid cells in the dermis and hypodermis, without the presence of mast cells, as a manifestation before acute lymphoblastic leukemia is presented in this article.

Chronic Myeloid Leukemia Cutis: A case report

Leukemia cutis [LC] is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the sub cutis, resulting in clinically identifiable cutaneous lesions. LC may follow, precede, or occur concomitantly with the diagnosis of systemic leukemia.Here we present a case report of Chronic Myeloid Leukemia [CML] cutis in a 32-year-old female who was a known case of CML and presented with multiple erythematous nodules all over her body. Cytological study from the aspirates of these nodules revealed MPO [Myeloperoxidase] positive immature cells from myeloid series.

Monocytic leukeima masquerading as a cutaneous lesion

Cutaneous lesions preceding a leukaemia are extremely rare and are referred to as ‘aleukaemic leukaemia cutis’. We present a case of acute monocytic leukaemia where skin infiltration of leukemic cells preceded any blood or bone marrow evidence of leukaemia. A 67-year-old woman presented with multiple cutaneous nodules all over the body of 3 months duration. Cutaneous examination showed multiple erythematous papules and plaques which were present over the face, trunk, extremities and back. Patient was evaluated at a nearby facility and was found to have normal blood parameters (TLC- 7130/cmm, N-57% L-34% M-09%). A skin biopsy done revealed infiltration of the dermis by atypical cells suggestive of a hematolymphoid malignancy. The patient was then shifted to our institution for tertiary care management. The blood counts over a period of one month showed gradually increasing TLC from an initial normal blood count to one showing absolute monocytosis (TLC-25500/cmm, AMC-3825/cmm) and finally abnormally high TLC (TLC-154050/cmm) with 79% monoblasts and promonocytes suggestive of acute leukaemia. A repeat skin biopsy again showed infiltration of atypical cells in the dermis. IHC done showed the atypical cells to be positive for monocytic markers (CD14, CD64). The patient had now started exhibiting systemic findings corroborating with the cutaneous lesions and skin biopsy. Bone marrow aspirate was hypercellular and showed replacement by monoblasts (82%). Cellular morphology was suggestive of AML-M5. Bone marrow biopsy showed a diffuse replacement of marrow by immature cells/blasts. Flow cytometry reports were also positive for monocytic markers. The patient was hence diagnosed as AML M5 with cutaneous metastasis/leukemia cutis and was immediately started on chemotherapy (3+7). Post induction phase, the patient was in remission and her skin lesions subsided. She was subsequently discharged and advised regular OPD follow up for maintenance therapy. This case is reported for its rarity.

Primary cutaneous lymphomas in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): A series of 12 cases

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is associated with an increased risk of a second malignancy. We conducted a retrospective clinicopathologic review of 12 patients with CLL/SLL who developed a second lymphoma in the skin. Demographic data, clinical information, and histopathology from 31 biopsies were recorded. Cases of secondary cutaneous involvement by CLL/SLL (leukemia cutis) and non-primary cutaneous lymphomas were excluded. A wide variety of primary cutaneous lymphomas was identified, including classic mycosis fungoides (3), cutaneous marginal zone lymphoma (2), primary cutaneous peripheral T-cell lymphoma unspecified (2), folliculotropic mycosis fungoides (1), Sézary syndrome (1), cutaneous gamma-delta T-cell lymphoma (1), cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma (1), and cutaneous anaplastic large cell lymphoma (1). A male predominance was observed, and the average age was 74.1 years. In all patients, CLL/SLL predated the development of the second lymphoma, which was aggressive in the majority of cases (58%). Aggressive cytotoxic T-cell lymphomas, generally rare neoplasms, were relatively common (30%). CLL/SLL patients may develop a second lymphoma in the skin, which may be aggressive. Atypical cutaneous lymphoid infiltrates in this patient population should not be assumed to represent secondary CLL/SLL involvement and require thorough immunohistochemical analysis.

Specific cutaneous infiltrates in patients with haematological neoplasms: a retrospective study with 49 patients.

Haematological neoplasms account for around 9% of all cancers, and they are recognised as an important cause of skin infiltration. However, studies analysing cutaneous metastasis of haematological neoplasms are scarce. We describe the clinical spectrum and outcomes of specific cutaneous manifestations of leukaemias, lymphomas, multiple myeloma (MM), and blastic plasmacytoid dendritic cell neoplasm (BPDN) and make a review of the literature. Data from 49 patients diagnosed with secondary cutaneous infiltration of systemic haematological neoplasms over the last 10years in a tertiary dermatology centre were retrospectively collected, and clinical-evolutive features were analysed. Most cases were lymphoma (44.9%, n=22), followed by leukaemia cutis (38.8%, n=19), secondary plasmacytoma (10.2%, n=5) and BPDN (6.1%, n=3). Nodules were the predominant type of lesion, and most patients presented with multiple (≥3) lesions. In 51% (n=25) of cases, cutaneous infiltration was detected before the diagnosis of the underlying malignancy. The patients in diverse nosological groups did not differ in terms of survival (P=0.052). We recognise the clinical heterogeneity of specific cutaneous infiltrates. The high proportion of cases in which skin involvement was key to the diagnosis of systemic malignancy emphasises the role of the dermatologist in recognising and correctly managing these patients.

Leukaemia cutis for clinicians, a literature review.

Leukaemia cutis (LC) describes infiltration of the skin by leukaemia cells, resulting in clinically identifiable cutaneous lesions. LC has a wide range of clinical manifestations, which can make it difficult to distinguish LC from other skin changes. In a group of patients, LC can be the first manifestation of leukaemia, therefore skin biopsy is crucial for the diagnosis. In this mini review, we discuss various types of leukaemia most frequently represented in leukaemia cutis, in both children and adults and skin changes in multiple myeloma, focusing on the clinical presentation of LC and prognosis in patients.

Leukemia Cutis as an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia (CLL).

Background and Objective:Cutaneous infiltration by Chronic Lymphocytic Leukemia (CLL) is a rare complication. The clinical presentation, impact of it on disease prognosis, and the proper treatment choice are not clear. Here in our review, we try to answer these questions.Acquisition of evidences:A systematic search of PubMed, and Google Scholar for English language articles published from Jan 2000 to June 2019.Synthesis of evidences:A total of 56 cases were identified, with a median age of 66 years. Of these cases 43 were males and 12 were females, and one missing data, with a ratio of 3,6:1. Head and neck were most commonly involved. The commonest clinical presentation was papulonodular lesions, and the majority were diagnosed at an early stage. CLL skin involvement at the site of old herpetic lesions was common. Because of the rarity of the disease, treatment modalities varied widely, and there are no consensus on treatment. The majority were treated with chemotherapy. In general, 35 (77.8% - of the non-missing data) patients responded to treatment (25 patients had a complete remission and 10 a partial remission). All patients ≤60 years had an early-stage disease, on the other hand, all patients with advanced-stage were >60 years.Conclusion:Patients with early-stage and localized leukemia cutis can benefit from observation alone strategy, while intervention in young patients with advanced disease is warranted. Skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with a very low progression rate.

Leukemia Cutis Emerging at the Site of Previous Catheter Insertion

Leukemia Cutis Emerging at the Site of Previous Catheter Insertion

Leukemia Cutis Presenting as Non-healing Ulcers with Marginal Umbilicated Nodules

Leukemia Cutis Presenting as Non-healing Ulcers with Marginal Umbilicated Nodules

15102 Not so Sweet: A confounding case of histiocytoid sweets in a leukemic patient

A 37-year-old Caucasian man with history of chronic myeloid leukemia (CML), not in remission, and Sweet syndrome (SS) presented for evaluation of a rash present for 1 month which had worsened in the prevceding 2 weeks. At the onset of rash his oncologist was concerned for blast crisis due to rapidly increasing WBC, and a biopsy was taken which was concerning for leukemia cutis (LC). At the time of our exam, the patient was afebrile with elevated WBC and otherwise unremarkable labs. He had countless indurated erythematous crusted papules and pustules, some with necrosis, coalescing into plaques on the face, scalp, upper and lower cutaneous lips, upper back, chest, and bilateral upper extremities.

Leukemia Cutis: A Systematic Review

Leukemia cutis (LC) is a rare cutaneous infiltration of extramedullary neoplastic hematopoietic cells with a paucity of data on their management, given that most cases are from individual case reports or case series, which further impact outcomes. This review aims to investigate the clinical characteristics of LC and highlight our cytogenetic findings that could contribute to our growing understanding and help reshape the prognosis of this rare but deadly condition. Patients and methods PubMed, Medline, ScienceDirect, and Scopus databases searched for "Leukemia Cutis" case reports from January 2000 to July 2020 pooled with a case from our institution. Results We included 184 biopsy-proven LC cases. Male: female ratio was 1.49:1. Mean age at diagnosis (± SD) was 48.9 (±25.9) years. Regarding age groups, 17 (9.2%), 16 (8.7%), 14 (7.6%), 12 (6.5%), 16 (8.7%), 29 (15.8%), and 80 (43.5%) patients were noted in the age groups of <1, 1-19, 19-30, 31-40, 41-50, 51-60, and >60 years, respectively. The demographics and clinical features of LC are summarized in Table 1. The presenting finding was LC in 66 (35.8%) cases, with an average time-to-leukemia diagnosis of 8.1 months (range, five days-72 months), and aleukemic LC (ALC) in 17 (9.2%) cases. Mean leukemia-to-LC diagnosis interval was 25.6 (range, 0-180 months). Acute myeloblastic leukemia (AML) was the most common type, found in 82 (44.5%) cases, out of which, M5, M4, and M2 variants were predominant at 21.9%, 9.7%, and 9.7%, respectively. Sixteen (8.7%) cases were secondary to acute lymphocytic leukemia (ALL), out of which 56.2% were B-cell lineage. Eleven (5.9%) cases were secondary to chronic lymphocytic leukemia (CLL). Other less common types were chronic myelomonocytic leukemia (CMML), myelodysplastic syndromes (MDS), chronic myeloid leukemia (CML), and acute promyelocytic leukemia (APL) in 9 (4.9%), 7 (3.8%), 5 (2.7%), and 5 (2.7%), respectively. The most common treatment modality was chemotherapy in 109/133 (81.9%) cases with the available data, out of which, 80 (73.4%) had chemotherapy alone, 16 (14.7%) had chemotherapy plus stem cell transplantation (SCT), 8 (7.3%) had chemotherapy plus radiotherapy, 3 (2.8%) had chemotherapy plus surgery and radiotherapy, 1 (0.9%) had chemotherapy plus radiation and SCT, and 1 (0.9%) had chemotherapy plus surgery. Mean duration of follow-up was 11 months (range, 1 day-100 months). In terms of outcomes, 61 (33.15%) patients were alive upon follow-up, out of which, 19 (31.1%) in remission, 18 (29.5%) disease-free, 17 (27.9%) with persistent disease, 2 (3.3%) had a recurrence, and 5 (8.2%) outcome not mentioned. Moreover, 91 (49.46%) patients died from disease. For the reported data, the average interval from leukemia diagnosis to death was 4.4 months (range, 3 days-15 months) for AML and 7.6 months (range, four days-25 months) for ALL (Table 2). Interestingly, at the time of our patient's LC diagnosis in our institution, cytogenic analysis revealed a novel inv(11)(p15q23) chromosomal aberration that herald MDS-to-AML transformation. Discussion In this review, several findings are noteworthy. First, males were more commonly affected. Second, 109 (59.2%) patients were older than 50 years of age. Third, LC noted as the initial presentation of systemic disease in more than a third of patients, whereas ALC was the initial presentation in only around 9% of patients. Fourth, multiple cutaneous lesions were more prevalent, with nodules being the most common presentation. Fifth, AML was the most predominant type overall, found in almost 45% of cases, followed by ALL, CLL, CMML, and other less common types. Sixth, chemotherapy was the most common treatment modality overall in more than 80% of patients with reported data. Seventh, almost half of patients died from the disease or complications related to it. Distinctly, very few studies in the literature reported this unique AML association with chromosome 11 aberrations. Conclusion LC is relatively rare and has a dismal prognosis. It most likely presents as the initial manifestation of leukemia, and physicians could easily misdiagnose this condition if managed without a biopsy. In this study, we intend to promote early recognition among physicians and highlight our unique cytogenetic findings. This could support future endeavors and develop novel patient-specific therapeutic strategies that exploit chromosomal aberrations amidst possible leukemogenic mechanisms. Disclosures No relevant conflicts of interest to declare.

A Phase II Study of Bisantrene in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background Relapsed/refractory acute myeloid leukemia (R/R AML) remains a significant therapeutic challenge and while meaningful therapeutics gains have been achieved with the introduction of novel agents, clinical outcomes remain unsatisfactory. Anthracyclines constitute an essential component of induction chemotherapy for AML patients, however owing in part to the cardiotoxicity concerns, they are not broadly prescribed in R/R AML settings. Bisantrene, an anthracene with anthracycline-like activity, was shown in earlier studies to be an effective salvage therapy in R/R AML with no discernible cardiotoxicity. In this study, we assessed the clinical efficacy of bisantrene in a cohort of heavily pre-treated R/R AML patients. Aims To investigate the safety and efficacy of bisantrene in adult patients with R/R AML. Methods This phase 2, single center study (NCT03820908) enrolled adult R/R AML to receive bisantrene (250 mg/m2 daily for 7 days) which was administered via an intravenous infusion over 2 hours on days 1-7. Patient therapy was limited to one completed cycle of bisantrene including those who had achieved a partial response. Disease assessment included routine blood work and bone marrow studies which were performed at baseline and subsequently at blood count recovery or suspected disease progression. Next generation sequencing (NGS) was performed at baseline for all patients with adequate pre-study samples. Results In all, 10 patients were recruited to the study with a median of 3 lines of prior therapy including 7 patients who had relapsed following allogeneic stem cell transplantation. With regard to disease burden, three patients had an antecedent myeloid disorder while 4 patients had extramedullary disease at study recruitment. The most frequently reported grade ≥3 treatment attributed hematologic AE was thrombocytopenia whereas the most frequently reported grade ≥3 treatment attributed non-hematologic AE was mucositis. Of the ten patients, one (10%) achieved a complete remission and three patients achieved a partial remission resulting in an overall response rate of 40% with one patient being bridged to transplantation. NGS of patient samples identified a wide array of mutations associated with activated signaling, splicing, and epigenetic modification (table 1). Conclusion In conclusion, in the present study bisantrene induced clinical responses in 4 of 10 patients with R/R AML with acceptable toxicity. Given its marked activity in patients with leukemia cutis, chroromas and CNS disease, we speculate that bisantrene-based chemotherapy may have a significant applicability in patients with extramedullary disease. In view of the observed efficacy and low related toxicity, a follow-up study combining bisantrene with complementary anti-leukemic therapy is planned. Disclosures Canaani: Abbvie: Consultancy, Honoraria, Research Funding. Benjamini:Abbvie Inc: Consultancy, Research Funding. Avigdor:Takeda, Gilead, Pfizer: Consultancy, Honoraria; Janssen, BMS: Research Funding.

Clinical Characteristics, Management, and Outcomes of Patients with Aleukemic Leukemia Cutis: A Systematic Review

Introduction Aleukemic Leukemia cutis (ALC) is the primary extramedullary cutaneous infiltration of neoplastic leukemic cells that occasionally precede systemic leukemia diagnosis. This study aimed to investigate the clinical characteristics, management, and outcomes of ALC patients to expand our knowledge of this rare entity. Patients and methods PubMed, ScienceDirect, Scopus, Web of Science, CINAHL, SpringerLink, and Google Scholar academic databases search for "Aleukemic Leukemia Cutis" case reports between 2000 and 2020. Results The mean age at the time of diagnosis of the 32 histologically-proven ALC cases included in the study was 38.8 (range, 0-85) years with a male: female ratio of 1.13:1. Regarding the age groups, we recorded 5 (15.6%), 6 (18.8%), 3 (9.4%), 3 (9.4%), 1 (3.1%), 4 (12.5%), and 10 (31.2%) patients in the age groups of <1, 1-19, 19-30, 31-40, 41-50, 51-60, >60 years, respectively. The mean interval between ALC presentation and leukemia-diagnosis was 9.7 (range, 0-48) months, including a patient with a 20-months interval who underwent chemotherapy and cord-blood stem cell transplantation (SCT) later found to have acute myeloblastic leukemia (AML) relapse at 84-months from the initial ALC diagnosis. Lesions were multiple in 87.5% and solitary in 12.5% of cases, located most commonly, in decreasing order, in the trunk, extremities, head, and neck in 36.4%, 29.1%, 27.3%, and 7.2 % of cases, respectively. Nodules, macules, papules, and plaques were the four most common lesions in 32.4%, 20.6%, 20.6%, and 11.8% of cases, respectively, whereas swelling, patches, and ulcers were uncommon. Lesions were described as erythematous and violaceous in 35.3%, and 2.9% of cases, respectively, with mean tumor dimensions of 4.7 (range, 0.2−13) cm. Following ALC diagnosis, a clinically identifiable systemic disease was detected in 12/32 (37.5%) cases, out of which AML was the most common type, found in 7 (58.3%) cases, followed by precursor B-cell acute lymphoblastic leukemia (preB ALL) in 2 (16.6%) case. Less common types were myelodysplastic syndromes (MDS), acute promyelocytic leukemia (APL), and biphenotypic acute leukemia (BAL) constituted 3 (25.0%) cases collectively. Among 25 patients with available data on treatment modalities, the most common overall was chemotherapy in 22 (88.0%) cases, out of which 13 (59.1%) had chemotherapy alone, 6 (27.3%) had chemotherapy plus SCT, and 3 (13.6%) cases had chemotherapy plus either radiotherapy, surgery plus chemoradiation or electron beam therapy. The mean duration of follow-up was 16.6 months (range, seven days-100 months). Furthermore, of the 27 patients with reported data, 12 (44.4%) were alive upon follow-up, out of which 7 (58.3%) disease-free, 4 (33.3%) in remission, and 1 (8.3%) with persistent disease, and fifteen (55.6%) patients died of the disease. Discussion Our study's main findings are as follows: First, 14 (43.7%) patients were older than 50 years of age, with an incidence only slightly higher in males than females. Second, lesions were mostly multiple and may take various forms of presentation, with nodules being the most common finding in over one-third of cases. Third, concurrent diagnosis of systemic disease was reported in 37.5% of cases with AML constituting 58.3% of cases. Fourth, chemotherapy was the mainstay of the treatment, followed by SCT in almost one-third of the cases. Notably, more than half of the patients died within months after ALC diagnosis. Conclusion ALC pathology remains not well delineated, and despite all assorted interventions; still, most patients succumb within months of diagnosis. Increased awareness among primary care physicians and dermatologists, amalgamated with further research to further investigate its pathology and determine extramedullary molecular targets, could eventually improve outcomes of this rare but life-threatening ailment. Disclosures No relevant conflicts of interest to declare.

Genomic Analysis of Congenital Myeloid Sarcoma Identifies Significant Bone Marrow Involvement in the Absence of Morphologic Blasts

Myeloid sarcoma is a tumor mass consisting of blasts at extramedullary sites, most frequently the skin and soft tissues. Skin involvement, also termed leukemia cutis, is a well-described entity in congenital leukemia and is present in approximately 50% of patients diagnosed within the first 4 weeks of life. Most cases of congenital leukemia cutis harbor KMT2A rearrangements, as do up to 80% of cases of infantile leukemia, and are typically accompanied by bone marrow involvement. Here we describe a rare CIC-rearrangement as the driver mutation for a case of congenital cutaneous myeloid sarcoma in a newborn female who was noted at birth to have a violaceous, nodular rash. Skin biopsy of the nodular rash shortly after birth with immunohistochemical staining was consistent with myeloid sarcoma. Bilateral bone marrow aspirates and biopsies were also performed, but failed to reveal an aberrant blast population by morphology and flow cytometry. Cytogenetics of the cutaneous myeloid sarcoma was significant for t(10;19)(q23;q13.2) and fluorescence in situ hybridization performed on the tumor confirmed a CIC-rearrangement. CIC-rearranged sarcomas are a new entity of undifferentiated small round cell sarcoma characterized by fusion events involving the CIC gene but are not a known to be driver mutations in myeloid neoplasms. Despite the absence of a blast population in the bone marrow, 75% of analyzed metaphases carried the t(10;19)(q23;q13.2). To further explore the underlying genomic events, whole genome, exome, and transcriptome sequencing was performed on both sarcoma and bone marrow specimens. Sequencing revealed an in-frame CIC-NUTM2A fusion gene present in both the skin and the bone marrow which has been previously described in a single case of undifferentiated soft tissue sarcoma. There were no large-scale chromosomal losses or gains and no copy neutral loss of heterozygosity events. Two exonic single nucleotide variations (SNVs) were detected, both of which were limited to the skin sarcoma and not predicted to be pathogenic. In vitro and in vivo modeling demonstrated that the CIC-NUTM2A fusion protein was highly leukemogenic. Colony forming assays performed using transduced murine bone marrow revealed that the CIC-NUTM2A fusion conferred self-renewal in contrast to CIC, NUTM2A, and the reciprocal NUTM2A-CIC product which failed to serially replate (p<0.001). Transplantation of CIC-NUTM2A modified murine bone marrow cells resulted in a fully penetrant myeloid leukemia with a median survival of 21 days in primary transplants and 16 days in secondary transplants. Transcriptome analysis of these tumors revealed a distinct gene expression profile when compared to several classic myeloid associated fusion genes including AML1-ETO and MLL-AF6. To further understand the acquisition of a malignant phenotype by morphology between the bone marrow and the sarcoma, targeted deep sequencing was performed for all tier 1, 2 and 3 mutations identified by whole genome and exome sequencing. A shared ancestral clone was identified in both specimens along with three subclones specific to the sarcoma. Four SNVs acquired in the sarcoma were found to be present in regulatory regions of genes that were also differentially expressed between the sarcoma and the bone marrow including C6orf120, SMURF1, TJAP1, and PID1. PID1 was found to be downregulated in the malignant sarcoma specimen and has been previously shown to be a regulator of the AKT/PI3K pathway. Low PID1 expression has been associated with poor outcomes in other malignancies, including pediatric glioblastoma. A genome wide CRISPR screen of our CIC-NUTM2A positive murine leukemia cells revealed an enrichment for PID1 deficient cells as well as PTEN confirming the cooperativity between CIC-NUTM2A and the AKT/PI3K pathway (p=0.009 and p=0.005 respectively). In conclusion, we describe a rare fusion gene, CIC-NUTM2A, which leads to an aggressive myeloid malignancy in both humans and mice. Targeted deep sequencing demonstrated the clonal evolution from the bone marrow and acquisition of a cooperating mutation targeting the AKT/PI3K pathway in a subset of extramedullary cells that led to morphologic transformation. A thorough interrogation of the bone marrow in patients with myeloid sarcoma is warranted even in the absence of morphologic and immunophenotypic blasts by flow cytometry to optimally track residual disease during treatment. Disclosures No relevant conflicts of interest to declare.

Dermatologic manifestations in pediatric patients after liver and HSCT: A 20-year retrospective cohort study.

LT and HSCT are now potentially curative treatments for many medical conditions. Dermatologic manifestations are one of the sequelae after transplantation. To study the prevalence and associated risk factors of dermatologic manifestations after pediatric LT and HSCT. A 20-year retrospective cohort study was conducted in children, aged ≤15years, who received LT or HSCT from January 1, 1997, to December 31, 2017. Medical records were reviewed for data collection until December 31, 2018. A total of 70 LT and 51 HSCT recipients were included. The percentages of overall dermatologic manifestations after LT and HSCT were 64.3% and 64.7%, respectively. Viral infection was the most common manifestation in both groups, with mucocutaneous HSV infection as the most prevalent. One HSCT recipient developed leukemia cutis. GVHD was revealed in 27.5% of HSCT recipients. Impetigo and xerosis were significantly observed in patients using azathioprine and prednisolone. Approximately two-thirds of pediatric LT and HSCT recipients experienced dermatologic manifestations, potentially associated with immunosuppressive agents. Thus, regular skin examination and optimized immunosuppression would be beneficial in these recipients.

Leukemia Cutis in a Patient with Rare Indolent T-Prolymphocytic Leukemia - A Case Report and Review of the Literature

Abstract Introduction/Objective T-cell prolymphocytic leukemia (T-PLL) is rare, comprising 2% of mature lymphocytic leukemias in adults. Clinical course is usually aggressive, however, 20-30% patients can have an indolent early phase. Most patients present with extensive disease with peripheral blood lymphocytosis, hepatosplenomegaly, and lymphadenopathy. T-PLL has a higher incidence in patients with ataxia-telangiectasia. Methods We present a case of a 67-year old man with history of somatic mutation of ataxia-telangiectasia gene (ATM) and multiple malignancies, including melanoma, skin and laryngeal squamous cell carcinomas, adrenal adenoma and spindle cell lung tumor (diagnosed on biopsy), who developed leukemia cutis during an indolent phase of T-PLL. Results Initial diagnosis of T-PLL was on routine complete blood count when patient had mild atypical lymphocytosis (5.5 x 109/L). Flow-cytometry immunophenotyping detected CD4 + 8 positive mature T-cells with no aberrant loss of T- cell antigens, and molecular studies confirmed clonal T-cell receptor beta and gamma gene rearrangements. T-PLL associated leukemia cutis was diagnosed on a leg skin nodule biopsy 10 months later. Subsequent bone marrow biopsy demonstrated low level involvement by T-PLL. The patient’s T-PLL followed an indolent trajectory for three years and treatment was withheld until symptomatic presentation. Rapid disease progression was heralded with emergence of widespread T-PLL leukemia cutis, rapidly increasing lymphocytosis, extensive lymphadenopathy, splenomegaly and increasing LDH levels. Conclusion Skin involvement is reportedly identified in 20% to 50% of T-PLL cases in some series. Skin manifestations can be heterogenous with a broad clinical differential. T-PLL associated leukemia cutis may not be recognized owing to the overall low incidence and in skin lesions appearing during an undiagnosed indolent early phase of T-PLL.We highlight the importance of accurate evaluation of non-specific skin lesions in early detection of T- PLL. Being aware of this diagnosis and early engagement in an interdisciplinary approach may allow for better outcomes of this aggressive malignancy.

AML-030: The Diagnostic Yield and Safety of Skin Biopsies in Patients with Acute Myeloid Leukemia During Intensive Chemotherapy - A Retrospective Cohort Study

Context Skin eruptions are common in acute myeloid leukemia (AML). However, data on the safety and diagnostic yield of skin biopsies in affected patients are scarce. Objective To evaluate the yield and safety of skin biopsies obtained from adult patients with AML during hospitalization for intensive chemotherapy. Methods The database of a tertiary university-affiliated medical center was retrospectively searched for patients with AML who underwent biopsies for skin eruptions during hospitalization in 2007-2018. Clinical, laboratory, and outcome data were collected. Results Of 216 consecutive patients diagnosed with AML, we identified 35 patients who underwent 37 skin biopsies: 22% at presentation and the remainder after chemotherapy commencement. Histopathological diagnoses were drug eruption (24.3%), infection (11%), leukemia cutis (16.2%), Sweet syndrome (5.5%), and a reactive process (8%); in 35% of biopsies, findings were inconclusive. Tissue cultures, performed in 16 patients, were positive in 4 (25%). Only in 8% of cases did the biopsy results lead to a change in management. One patient had bleeding and fever as a result of the biopsy. Conclusions Our study suggests that skin biopsies are relatively safe to perform in patients with AML undergoing intensive chemotherapy, although their diagnostic yield is limited.

Leukaemia cutis as a specific skin involvement in chronic myelomonocytic leukaemia and review of the literature: Acknowledgments.

The skin involvement of myeloid leukaemia is conventionally divided into specific malignant lesions and non-specific benign lesions, and these categories are also applicable in chronic myelomonocytic leukaemia (CMML). According to the 2016 World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues, CMML is defined as a myeloid neoplasm with characteristics of myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs). As a specific cutaneous sign of extramedullary infiltration, leukaemia cutis (LC) is a rare occurrence in patients with CMML, and only approximately 89 cases have been reported in the literature thus far. The clinical features of LC are varied, and LC in CMML exhibits heterogeneous histopathologic features, with manifestations as cutaneous nodules or papules that are composed of blast cells showing either granulocytic or monocytic differentiation. Skin biopsy and further immunohistochemical examination are essential at the time of diagnosis to evaluate pathological type and determine the clinical course. Generally, once diagnosed as LC in CMML, this unusual skin lesion might be an indicator of transformation to acute myeloid leukaemia (AML) and is associated with a poor prognosis. The main treatment is allogeneic stem cell transplantation (ASCT). Therefore, early diagnosis and accurate identification have important therapeutic and prognostic significance in CMML patients with skin infiltration.