Manifestation Of Chronic Lymphocytic Leukemia Research Articles

Behçet's disease-like clinical manifestations of chronic lymphocytic leukemia during good response to ibrutinib.

Behçet's disease-like clinical manifestations of chronic lymphocytic leukemia during good response to ibrutinib.

Acral Solitary Nodule as a First Clinical Manifestation of Chronic Lymphocytic Leukemia

Leukemia cutis is a rare cutaneous manifestation of chronic lymphocytic leukemia (CLL) which mostly occurs in the late stages of the disease. We reported an unusual case of a patient with leukemia cutis that developed before the diagnosis of CLL and mimicked cutaneous leishmaniasis (CL). A 52-year-old female presented with an ulcerative nodule on the right forearm. The lesion initially was suspected of being cutaneous leishmaniasis; however, the examination of skin lesion biopsy revealed a dense, diffuse, and monomorphous infiltration of lymphocytes in the dermis. Furthermore, immuno-histochemistry analysis of skin lesion biopsy was indicative of small lymphocytic lymphoma (SLL). The result of laboratory tests showed high white blood cell and lymphocyte counts. The results of bone marrow smear, flow cytometric analysis, and computed tomography of the abdomen and pelvis were suggestive of CLL/SLL (stage I). This case has clinical implications for early diagnosis and management of CLL/SLL.

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.

Cerebral Localization of Chronic Lymphocytic Leukemia Simulating Progressive Multifocal Leukoencephalopathy: The Lessons from a Case

Background: Central neurological involvement is the most frequent extra hematological manifestation of chronic lymphocytic leukemia; it is multifactorial and rarely due to a cerebral localization of the disease. We report a case of cerebral localization of chronic lymphoid leukemia whose clinical and radiological aspects were very suggestive of progressive multifocal leukoencephalopathy. Case Presentation: A 65-year-old patient who was HIV-negative (human immunodeficiency virus), had consulted for bilateral axillary, cervical and inguinal lymphadenopathy associated with major asthenia and hyper lymphocytosis (lymphocyte count was 11 giga/l). Chronic lymphocyticleukemia with TP53 mutation was diagnosed and treatment with Ibrutinib 420 mg/day was initiated. After 2 months of treatment, the evolution was marked by the onset of neurological disorders whose clinical-radiological presentation and temporal evolution had led to the diagnosis of progressive multifocal leukoencephalopathy. In the absence of virological evidence in the cerebrospinal fluid analysis, a stereotactic biopsy of the brain lesions had been performed, making it possible to formally rule out this infectious hypothesis and to demonstrate cerebral invasion by tumour cells. Immuno-chemotherapy combining Rituximab-Cyclophosphamide-Doxorubicin-Vincristine-Prednisone-Ibrutinib (RCHOP-Ibrutinib) with intrathecal chemotherapy resulted in a very good clinical-radiological response. Conclusion: The appearance of neurological manifestations in the context of chronic lymphocytic leukemia must systematically lead to a search for a cerebral localization of the disease. In the absence of virological evidence in the cerebrospinal fluid, any suspicion of progressive multifocal leukoencephalopathy in this context should lead to the histological study of brain lesions.

Leukemia Cutis As an Early Presentation or Relapsing Manifestation of Chronic Lymphocytic Leukemia

Introduction Cutaneous infiltration (Leukemia cutis) by CLL is regarded as specific sign of skin involvement, these findings can vary in presentations; they can be localized or generalized in the form of erythematous papules, plaques, nodules, and large tumors, however ulceration is uncommon. Skin lesions in general can be seen in 25% of patients with CLL. It is unclear what is the impact of cutaneous infiltration by CLL on prognosis, mainly because most cases are sporadic, either in case reports or series, with no consistency in the modality of treatment. Patients and methods A systematic search of the Medline database (PubMed), Google Scholar was performed to identify English language articles published from Jan 2000 to June 2019 with the following search terms: Leukemia cutis - CLL, cutaneous - CLL, skin - CLL, cutaneous - chronic lymphocytic leukemia, skin - chronic lymphocytic leukemia. Only patients with confirmed CLL Leukemia cutis were included in this analysis. Results A total of 56 cases were identified, with median age of 66 years (range from 39-90), of these cases 43 (76.8%) were males and 12 (21.4%) were females, with ratio of 3.6 : 1. Head and neck were the most common involved sites, interestingly it was very common on the earlobes, followed by trunk and extremities. The most common clinical presentation was papulonodular skin lesions, others like erythematous patches were seen, but ulceration was uncommon. Most cases had leukemia cutis as the initial presentation of CLL. The median time before relapse with skin involvement was 5.5 years (range 1 to 21 years). Most patients were diagnosed at early stage. Majority were treated with chemotherapy, others managed by observation, local radiotherapy or chemoimmunotherapy. In general, 35 (62.5%) cases had cutaneous response to treatment (25 CR and 10 PR). Discussion CLL skin infiltration is not uncommon, but it is not well described in the literature, here in our review we revisited specific cutaneous infiltration by CLL, we emphasized on Leukemia cutis rather than general secondary skin manifestations in CLL. Many cases had CLL skin involvement at the site of old herpetic lesions, which raises the hypothesis of monoclonal B-cells antigenic recruitment, rather than true metastasis. Most presentations came as first sign of the disease, and mostly in early stage. It was also observed that skin infiltration by CLL does not affect prognosis, as most patients attained complete or partial remission with very low progression rate. Because of the rarity of the disease, treatment modalities varied widely, and there was no consensus on treatment, yet all treatment modalities resulted in cutaneous response rate of 62.5%. The best modality of treatment in cutaneous CLL is based on the staging, lesions distribution (localized vs. generalized) and co-morbidities. Conclusion Leukemia cutis is rare but rather a recognized complication of CLL, most likely presents as papulonodular lesions as initial sign of the disease, furthermore most patients present in early stage, it is observed that all patients ≤60 year old had early stage disease, patients with early stage and localized leukemia cutis can benefit from observation alone strategy, on the other hand all patients with advanced stage were >60 year old, and intervention in these patients is warranted, in other situations treatment is individualized based on staging, lesions distribution (localized vs. generalized) and comorbidities. Leukemia cutis did not affect the prognosis of the disease. Disclosures No relevant conflicts of interest to declare.

Whipple's Disease as the First Manifestation of Chronic Lymphocytic Leukaemia.

Whipple’s disease is a rare multisystemic infectious disease that can mimic lymphoproliferative disorders and must be considered in the differential diagnosis of febrile syndromes. The authors describe the case of a 55-year-old man who presented to the Emergency Department with dyspnoea and abdominal pain. He had a 2-month history of fever, night sweats, asthenia and unintentional weight loss. Upon clinical examination he had bilateral inguinal lymphadenopathy. Blood tests showed iron-deficit anaemia and high C-reactive protein. Abdominal ultrasound showed mesenteric and iliac adenopathies and hepatosplenomegaly. The patient was admitted to the Internal Medicine department for additional testing. Flow cytometry analysis of peripheral blood showed CD5-positive monoclonal B-cell expansion. Excisional biopsy of a retroperitoneal adenopathy guided by computed tomography showed periodic acid–Schiff-positive bacilli inside the macrophages, further identified as Tropheryma whipplei through polymerase chain reaction. Bone marrow biopsy showed a scarce positive CD5 lymphoid population and haematopoietic alterations related to infection. The patient started treatment for T. whipplei with complete symptom resolution. This is the first case describing the simultaneous diagnosis of Whipple’s disease and chronic lymphocytic leukaemia in a patient with constitutional symptoms, fever and lymphadenopathies.LEARNING POINTSWhipple’s disease can mimic lymphoproliferative disorders and should be considered in the differential diagnosis of lymphadenopathy and fever, even in the absence of gastrointestinal symptoms.Most patients with chronic lymphocytic leukaemia are asymptomatic, but a minority have B symptoms and increased risk of infections.An accurate clinical history and differential diagnosis are fundamental; if the authors had not had a high level of suspicion, this patient could have been diagnosed with just chronic lymphocytic leukaemia and may have died if Whipple’s disease had been left untreated.

Białaczka skóry w przebiegu przewlekłej białaczki limfocytowej leczona ibrutynibem

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Osmola M, Gierej B, Waszczuk-Gajda A, et al. A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib. Medycyna Paliatywna/Palliative Medicine. 2019;11(4):180-183. doi:10.5114/pm.2019.93186. APA Osmola, M., Gierej, B., Waszczuk-Gajda, A., Kłosowicz, A. D., Hałaburda-Rola, M., & Jędrzejczak, W. et al. (2019). A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib. Medycyna Paliatywna/Palliative Medicine, 11(4), 180-183. https://doi.org/10.5114/pm.2019.93186 Chicago Osmola, Małgorzata, Beata Gierej, Anna Waszczuk-Gajda, Agata D Kłosowicz, Marta Hałaburda-Rola, Wiesław Wiktor Jędrzejczak, and Grzegorz W Basak et al. 2019. "A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib". Medycyna Paliatywna/Palliative Medicine 11 (4): 180-183. doi:10.5114/pm.2019.93186. Harvard Osmola, M., Gierej, B., Waszczuk-Gajda, A., Kłosowicz, A., Hałaburda-Rola, M., Jędrzejczak, W., Basak, G., and Ziarkiewicz-Wróblewska, B. (2019). A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib. Medycyna Paliatywna/Palliative Medicine, 11(4), pp.180-183. https://doi.org/10.5114/pm.2019.93186 MLA Osmola, Małgorzata et al. "A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib." Medycyna Paliatywna/Palliative Medicine, vol. 11, no. 4, 2019, pp. 180-183. doi:10.5114/pm.2019.93186. Vancouver Osmola M, Gierej B, Waszczuk-Gajda A, Kłosowicz A, Hałaburda-Rola M, Jędrzejczak W et al. A rare manifestation of chronic lymphocytic leukaemia – leukaemia cutis treated with ibrutinib. Medycyna Paliatywna/Palliative Medicine. 2019;11(4):180-183. doi:10.5114/pm.2019.93186.

Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review.

ENWEndNote BIBJabRef, Mendeley RISPapers, Reference Manager, RefWorks, Zotero AMA Szukalski Ł, Sysakiewicz-Buda M, Męcińska-Jundziłł K, Białecka A, Czyż J, Czajkowski R. Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2019;36(6):778-780. doi:10.5114/ada.2019.91427. APA Szukalski, Ł., Sysakiewicz-Buda, M., Męcińska-Jundziłł, K., Białecka, A., Czyż, J., & Czajkowski, R. (2019). Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 36(6), 778-780. https://doi.org/10.5114/ada.2019.91427 Chicago Szukalski, Łukasz, Martyna Sysakiewicz-Buda, Kaja Męcińska-Jundziłł, Agnieszka Białecka, Jarosław Czyż, and Rafał Czajkowski. 2019. "Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review". Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii 36 (6): 778-780. doi:10.5114/ada.2019.91427. Harvard Szukalski, Ł., Sysakiewicz-Buda, M., Męcińska-Jundziłł, K., Białecka, A., Czyż, J., and Czajkowski, R. (2019). Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, 36(6), pp.778-780. https://doi.org/10.5114/ada.2019.91427 MLA Szukalski, Łukasz et al. "Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review." Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii, vol. 36, no. 6, 2019, pp. 778-780. doi:10.5114/ada.2019.91427. Vancouver Szukalski Ł, Sysakiewicz-Buda M, Męcińska-Jundziłł K, Białecka A, Czyż J, Czajkowski R. Cutaneous manifestation of chronic lymphocytic leukemia: a case report and a literature review. Advances in Dermatology and Allergology/Postępy Dermatologii i Alergologii. 2019;36(6):778-780. doi:10.5114/ada.2019.91427.

An unusual manifestation of chronic lymphocytic leukemia

An unusual manifestation of chronic lymphocytic leukemia

Chronic lymphocytic leukemia skin infiltration mimicking an ICD pocket infection: a case report

BackgroundWe are presenting a case report on an unreported and unusual cutaneous manifestation of chronic lymphocytic leukemia in a patient with an implantable cardioverter-defibrillator (ICD).Case presentationA 65-year-old man with a history of chronic lymphocytic leukemia (CLL), previously treated with chlorambucil, was referred in October 2013 for extraction of a single chamber ICD due to a suspected device-related infection in the pulse generator area (left-hand side of Fig. 1). The ICD system (Current VR, St. Jude Medical, USA) had been implanted in November 2009. The patient complained of painless erythema with pruritus in the pocket area. Inflammatory blood parameters were C-reactive protein 17.3 mg/L and leucocytes 29.0 × 109/L. Due to the atypical appearance of the pocket area we did not extract the device. Instead, we created an exploratory excision in the skin induration, which had been present for approximately 6 weeks, and conducted a microbiological and histological examination. All cultivation examinations were negative. However, we did histologically show skin infiltration by CD-5 positive low-grade B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL). Re-initiation of chemotherapy was not necessary and the skin induration completely disappeared within 2 months (right-hand side of Fig. 1).ConclusionsComplete removal of an ICD system carries considerable risk. In patients with a history of hematological disease, it is crucial to exclude cutaneous manifestations of the disease prior to device removal.

Genomic characterization of high-count MBL cases indicates that early detection of driver mutations and subclonal expansion are predictors of adverse clinical outcome.

High-count monoclonal B-cell lymphocytosis (MBL) is an asymptomatic expansion of clonal B-cells in the peripheral blood without other manifestations of chronic lymphocytic leukemia (CLL). Yearly, 1% of MBLs evolve to CLL requiring therapy; thus being critical to understand the biologic events that determine which MBLs progress to intermediate/advanced CLL. In this study, we performed targeted deep-sequencing on 48 high-count MBLs, 47 of them with 2-4 sequential samples analyzed, exploring the mutation status of 21 driver genes and evaluating clonal evolution. We found somatic non-synonymous mutations in 25 MBLs(52%) at the initial time-point analyzed, including 13(27%) with >1 mutated gene. In cases that subsequently progressed to CLL, mutations were detected 41 months (median) prior to progression. Excepting NOTCH1, TP53 and XPO1, which showed a lower incidence in MBL, genes were mutated with a similar prevalence to CLL, indicating the early origin of most driver mutations in the MBL/CLL continuum. MBLs with mutations at the initial time-point analyzed were associated with shorter time-to-treatment (TTT). Furthermore, MBLs showing subclonal expansion of driver mutations on sequential evaluation had shorter progression time to CLL and shorter TTT. These findings support that clonal evolution have prognostic implications already at the pre-malignant MBL stage, anticipating which individuals will progress earlier to CLL.

Mutations in Driver Genes and Changes in Clonal Dynamics Are Associated with Shorter Time to Treatment in MBL Cases

Mutations in Driver Genes and Changes in Clonal Dynamics Are Associated with Shorter Time to Treatment in MBL Cases

Central Nervous System Involvement By Chronic Lymphocytic Leukemia

INTRODUCTION. Although uncommon, involvement of the central nervous system (CNS) is the most common extramedullary manifestation of Chronic Lymphocytic Leukemia (CLL). Nonetheless, a broad array of conditions can lead to neurologic symptoms in CLL patients and distinguishing between clinically significant CLL involvement of the CNS and other etiologies can be challenging. The actual prevalence of CNS involvement by CLL is unknown, the only available data being case reports and small case series.METHODS. Between 01/1995 and 11/2014, 186 of the 4317 (4%) patients with CLL followed at our center underwent an MRI of the CNS (e.g. brain, spine) and/or a lumbar puncture (LP) with cerebral spinal fluid (CSF) analysis to evaluate neurologic symptoms. As the mere presence of CLL cells in the CSF is not diagnostic of clinically significant CNS disease, a final diagnosis of clinically significant CNS involvement by CLL was established by the collaborative review of the pathologist, neurologist and treating hematologist based on comprehensive work-up and multi-disciplinary evaluation.RESULTS. After evaluation, the etiology of neurologic symptoms was clinically significant involvement of the CNS by CLL in 19 (10%) patients, CNS Richter Syndrome (RS) in 15 (8%), infection in 42 (23%), autoimmune conditions in 31 (17%), other cancer in 9 (5%), and another etiology in 70 (37%). The sensitivity of LP to detect clinically significant CNS involvement by CLL was 89%, however its specificity was only 42% where CLL cells were also frequently observed in the CSF in concomitance with inflammatory processes, such as infections and autoimmune disease. Factors associated with clinically significant CNS involvement by CLL/RS were mutated IGHV (p=0.04), low CSF glucose (p=0.02), elevated CSF total nucleated cells (TNC)(p=0.004), lymphocytes (p=0.02) and CLL cells, both as absolute count (p=0.05) and percentage of TNC (p=0.02). Median OS among patients with clinically significant CNS involvement by CLL or RS were 21 and 11 months, respectively. Median OS for patients with neurological symptoms secondary to infection was 6 months, to autoimmune process was 63 months, to other cancers was 19 months, and to other non-CLL related etiologies was 37 months.CONCLUSIONS. Clinically significant CNS involvement by CLL and RS are rare conditions. Neurologic symptoms in patients with CLL are attributable to non-CLL-related etiologies in the majority of cases, even when CLL B-cells are present in the CSF. Analysis of the CSF has high sensitivity but limited specificity to distinguish clinically significant CNS involvement by CLL from other etiologies. Comprehensive evaluation is required before attributing neurologic symptoms to CLL. DisclosuresNo relevant conflicts of interest to declare.

Initial Diagnosis of a Common Hematological Malignancy in a Screening Colonoscopy

Extra-medullary (EM) manifestations of chronic lymphocytic leukemia (CLL) are relatively rare. Previous reports of EM-CLL suggest that the skin, CNS, and GI tract are the most commonly affected sites. In the majority of EM-CLL cases, EM involvement by CLL is only discovered after a primary diagnosis of CLL is made. GI involvement in CLL is generally associated with advanced stages of the disease in which the disease has transformed into large B cell lymphoma (i.e. Richter syndrome). Here we report a case of colonic involvement by CLL in a 50-year-old man who presented for a screening colonoscopy. This case is unique as the patient neither had a previous diagnosis of CLL nor experienced any of the associated symptoms. An asymptomatic 50-year-old man presented for his first screening colonoscopy. His past medical history was unremarkable except for prior squamous cell and basal cell skin carcinomas. Colonoscopy revealed grade 1 internal hemorrhoids and a 5 mm non-bleeding sessile polyp in the transverse colon which was resected for histological evaluation. Review of the specimen demonstrated multiple lymphoid aggregates composed of CD20 (+), CD5 (+), CD23 (+), LEF1 (+), Cyclin D1 (-) cells, which is consistent with involvement by CLL/small lymphocytic lymphoma (SLL). Blood counts were essentially normal, and no evidence of lymphoma or other pathologic abnormalities were found in the upper GI tract. A CT scan of the chest, abdomen, and pelvis revealed a small degree of lymphadenopathy above and below the diaphragm. The patient was diagnosed with stage IIIAE CLL/SLL. Further immunohistochemical analysis of the colon specimen indicated that the neoplastic cells did not express ZAP-70. Expression of ZAP-70 by the neoplastic cells is a reliable indication of the unmutated IgVH status in these cells. Considering that the unmutated IgVH status in the neoplastic cells is associated with a more aggressive clinical course of CLL, lack of ZAP-70 expression suggested an indolent course of disease. Immediate treatment was deferred, as the watch-and-wait approach is often the standard of care for low-risk CLL patients. This case is remarkable for at least two reasons: it demonstrates that the possibility of GI involvement in CLL should not be reserved only for later stages of the disease, and it emphasizes the need for the pathologists to remain vigilant for immunophenotype suspicious lymphoid aggregates even in the absence of a known CLL/SLL diagnosis.

Vasculitis Associated with Chronic Lymphocytic Leukemia

A patient is present who has chronic lymphocytic leukemia (CLL) and developed a vasculitis involving the skin and large vessels along with immune complex mediated glomerulosclerosis. Both vasculitis and immune complex nephritis are rare manifestations of CLL.

Thyroid nodule: first manifestation of chronic lymphocytic leukaemia

The presence of chronic lymphocytic leukaemia (CLL) cells in the thyroid gland is most likely due to a secondary involvement by a systemic disease. The reported incidence of CLL involving the thyroid is extremely low, representing about 3-4% of all thyroid lymphoproliferative neoplasm. We report a rare case of CLL presenting initially in the thyroid gland. Systemic disease was detected as a result of thyroid investigation. An 85 years old woman, with multinodular goiter without adenophaties, was referred to our department, carrying a fine needle aspiration biopsy (FNAB) report of a private institution referring "lymphoid monomorphic proliferation" and suggesting a "Core-needle biopsy" for further investigation. She was euthyroid (TSH-0.5 uU/mL (0.4-4.0), thyroid antibodies negative, including TRab). The patient denied systemic symptoms and at physical examination there were no adenophaties or organomegalies. FNAB analysis was repeated. Although the patient denied constitutional symptoms and there were no relevant findings in physical examination, technetium 99m thyroid gamagraphy (GG) and blood count were additionally asked. FNAB analysis concluded lymphocytic tiroiditis, but thyroid GG revelled global hypocaptation and blood count showed 173.4 x 109 leukocyte/L with 94% lymphocyte. An ecoguided FNAB with flow cytometry identified thyroid infiltration by monotonous population of blasts with phenotype consistent with CLL/malignancy of mature B-cells. CLL/malignancy of mature B-cells was also detected in peripheral blood analysis, suggesting systemic disease with secondary thyroid involvement. The patient started chemotherapy with rituximab and chlorambucil with good response. Pos-treatment GG revelled "Increased levels of uptake in the middle third of the right lower lobe, with low uptake of the remaining parenchyma". In conclusion, good communication with the pathologist can improve diagnostic accuracy and dictate appropriate therapy. The use of techniques such as flow cytometry, immunoglobulin gene rearrangements, and immunohistochemistry has improved diagnostic accuracy and obviated more invasive procedures, such as core needle or open surgery biopsy. Apart from chemotherapy, immunochemotherapy with anti-CD20 and anti-CD52 monoclonal antibodies can be used in the treatment of CLL.

Deregulated expression of circadian clock and clock-controlled cell cycle genes in chronic lymphocytic leukemia

Circadian rhythms are endogenous and self-sustained oscillations of multiple biological processes with approximately 24-h rhythmicity. Circadian genes and their protein products constitute the molecular components of the circadian oscillator that form positive/negative feedback loops and generate circadian rhythms. The circadian regulation extends from core clock genes to various clock-controlled genes that include various cell cycle genes. Aberrant expression of circadian clock genes, therefore, may lead to genomic instability and accelerated cellular proliferation potentially promoting carcinogenesis. The current study encompasses the investigation of simultaneous expression of four circadian clock genes (Bmal1, Clock, Per1 and Per2) and three clock-controlled cell cycle genes (Myc, Cyclin D1 and Wee1) at mRNA level and determination of serum melatonin levels in peripheral blood samples of 37 CLL (chronic lymphocytic leukemia) patients and equal number of age- and sex-matched healthy controls in order to indicate association between deregulated circadian clock and manifestation of CLL. Results showed significantly down-regulated expression of Bmal1, Per1, Per2 and Wee1 and significantly up-regulated expression of Myc and Cyclin D1 (P < 0.0001) in CLL patients as compared to healthy controls. When expression of these genes was compared between shift-workers and non-shift-workers within the CLL group, the expression was found more aberrant in shift-workers as compared to non-shift-workers. However, this difference was found statistically significant for Myc and Cyclin D1 only (P < 0.05). Serum melatonin levels were found significantly low (P < 0.0001) in CLL subjects as compared to healthy controls whereas melatonin levels were found still lower in shift-workers as compared to non-shift-workers within CLL group (P < 0.01). Our results suggest that aberrant expression of circadian clock genes can lead to aberrant expression of their downstream targets that are involved in cell proliferation and apoptosis and hence may result in manifestation of CLL. Moreover, shift-work and low melatonin levels may also contribute in etiology of CLL by further perturbing of circadian clock.

Recurrent penile ulcer as a manifestation of chronic lymphocytic leukaemia

Recurrent penile ulcer as a manifestation of chronic lymphocytic leukaemia

Endobronchial obstruction resulting in severe respiratory failure – A rare manifestation of chronic lymphocytic leukemia

Pulmonary involvement in chronic lymphocytic leukemia (CLL) has been previously described and is usually characterized by lymphocytic infiltration in the peribronchial interstitium. Endobronchial involvement is a very rare pulmonary manifestation of CLL unless a transformation to high-grade lymphoma occurs. In the present case we describe an elderly patient with indolent CLL in whom endobronchial involvement led to severe acute respiratory failure.

Massive ascites as a presenting manifestation of chronic lymphocytic leukemia

Ascites is not an uncommon manifestation of certain solid tumors like gastrointestinal malignancies, ovarian cancer and breast cancer. However, it is unusual to encounter ascites in patients with hematological malignancies especially chronic leukemia. The patient described here presented with massive ascites and blood lymphocytosis. Further studies confirmed the diagnosis of chronic lymphocytic leukemia with ascites. The ascitic fluid was exudative, consisting of mature-looking B-lymphocytes, which were morphologically and immunophenotypically similar to peripheral blood and bone marrow cells. The patient was treated with chemotherapy and achieved a good response and diminution of ascitic fluid accumulation.