Bone marrow reactive T-cell infiltrates have been frequently observed in patients affected by follicular lymphoma after rituximab treatment. In some studies, bone-marrow T-cell expansion has been associated with an effective anti-tumor response and favorable prognosis. In this manuscript, we report on a particularly brisk CD4+ T-cell reaction occurring after rituximab treatment for follicular lymphoma and involving the peripheral blood in addition to the bone marrow. Peripheral blood T-cell reaction was mainly composed of effector-memory CD4+ T cells and may reflect the expansion of an effective anti-tumor immunity.

BACKGROUND: Contrasting with the lymphopenia classically reported after administration of glucocorticoids, a lymphocytosis has been sometimes observed in patients after glucocorticoid administration. We here determine prospectively the timing and magnitude of methylprednisolone (mPDN)-induced lymphocytosis and study the effects of concomitant propranolol administration on lymphocyte count (Ly).
METHODS: Ly was measured before and 24 to 72hours after initiating mPDN treatment in 20 patients with immune-mediated inflammatory disorders (IMID). After one week, patients with increased Ly were divided in two groups receiving, in addition to mPDN, either propranolol or a placebo; Ly was determined 4 days later. Lymphocyte subpopulations and mPDN plasma levels were determined in subsets of the patients. Values are expressed as median with 25%-75% interquartile range.
RESULTS: A 73.4% (37-305) increase of Ly was observed in 18/20 patients as soon as 48 (48-72) hours after initiating mPDN (32mg; 16-32). Lymphocytosis (Ly≥4000/μL) was observed in 7 patients and hyperlymphocytosis (Ly≥5000/μL) in 4 of them. The increase in Ly was noted both for B and T cells. Median mPDN plasma levels (n=13) were 97.4ng/mL (IQR 67-489) and 3.2 (IQR 2.1-5.1) respectively 8hours and 24hours after oral mPDN administration. No significant change in Ly was shown under propranolol (p=0.570).
CONCLUSIONS: A morning lymphocytosis observed during mPDN treatment occurs in the very first days of mPDN administration. Our results do not support the hypothesis of an increased adrenergic tone responsible for this phenomenon. Identifying this unexpected etiology of lymphocytosis could mitigate the need for unnecessary supplementary investigations in clinical practice.

Headache and neurological deficits with cerebrospinal fluid (CSF) lymphocytosis (HaNDL) is a rare condition characterised by recurrent episodes of headache and transient neurological deficits. This case report presents a young patient initially diagnosed with hemiplegic migraine, having a normal brain CT, with focal cerebral perfusion mismatch not restricted to a single vascular territory on CT angiography. Brain MRI revealed a cytotoxic lesion of the splenium in the corpus callosum (CLOCC), a feature also reported in migraine. However, recurrent headaches with neurological deficits prompted further investigations with CSF analysis and brain MRI, confirming HaNDL and demonstrating reversibility of CLOCC. Recognising HaNDL as a differential diagnosis is essential in patients with recurrent headaches with focal neurological deficits, given the differences in therapeutic approach. The relationship between migraine and HaNDL is not fully understood, but they may share a pathophysiological link. Awareness of this is crucial for accurate diagnosis.

BACKGROUND Morvan fibrillary chorea (Morvan syndrome) is a rare disorder marked by a collection of neurological symptoms such as myokymia, peripheral nerve excitability, neuromyotonia, autonomic instability, memory impairment, and delirium. Morvan syndrome is suspected to occur through antibodies directed against voltage gated potassium channels (VGKC), and has been linked with several autoimmune conditions and hematologic malignancies. We present a case of Morvan syndrome in association with monoclonal B cell lymphocytosis. Upon our literature review, we believe this to be the first documented case of Morvan syndrome associated with monoclonal B cell lymphocytosis. CASE REPORT The present case report describes a 75-year-old man with Morvan\'s syndrome. The patient had a diverse neurologic presentation with encephalopathy, progressive neuropathic pain, muscle fasciculations, myokymia, sensory deficits, and Bell\'s palsy. Ultimately, a paraneoplastic antibody panel revealed a positive titer of contactin-associated protein-like IgG (CASPR) and VGKC antibody. Flow cytometry showed a small population of abnormal lambda-restricted B cells. Given his symptoms, positive CASPR antibody, and flow cytometry findings, he was diagnosed with Morvan syndrome associated with monoclonal B cell lymphocytosis. He was treated with IV methylprednisolone and IVIG, with immediate improvement in neurologic symptoms. CONCLUSIONS Morvan syndrome presents with a spectrum of neurologic symptoms and is associated with autoantibodies against VGKC through anti-CASPR2 antibodies. Classically, Morvan syndrome presents as a paraneoplastic disease secondary to thymomas. Our case demonstrates that there is an association between B cell lymphoproliferative disorders and Morvan syndrome.

BACKGROUND: The diagnostic complexities that arise in radiographic distinction between ectopic pleural thymoma and other thoracic neoplasms are substantial, with instances of co-occurring T-cell lymphocytosis and osseous metastasis being exceedingly rare.
METHODS: A 51-year-old woman was admitted to our hospital with dyspnea and chest pain. Upon imaging examination, she was found to have diffuse and nodular pleural thickening on the left side, collapse of the left lung and a compression in the second thoracic vertebrae. All lesions showed significant 18F-FDG uptake on 18F-FDG PET/CT examination. Furthermore, she exhibited T-cell lymphocytosis in her peripheral blood, lymph nodes, and bone marrow. After ruling out malignant pleural mesothelioma (MPM), lung cancer with pleural metastasis, and T-cell lymphoma, the definitive diagnosis asserted was ectopic pleural thymoma with T-cell lymphocytosis and bone metastasis.
CONCLUSIONS: Physicians need to expand their knowledge of the imaging features of ectopic pleural thymoma. Cases with T-cell lymphocytosis may exhibit increased aggressiveness and prone to bone metastasis.

Hyper-reactive malarial splenomegaly syndrome (HMSS) is a massive enlargement of the spleen due to an exaggerated immune response to repeated attacks of malaria.  Tropical splenomegaly syndrome (TSS) is the most frequent cause of massive tropical splenomegaly in malarious areas [1-2].  It is seen more commonly among residents of endemic areas of malaria.  It occurs mainly in tropical Africa, but also in parts of Vietnam, New Guinea, India, Srilanka, Thailand, Indonesia, South America, and the Middle East. TSS is characterized by massive splenomegaly, hepatomegaly, marked elevations in levels of serum IgM, and malaria antibody.

Our understanding of risk factors for the development of chronic lymphocytic leukemia (CLL) is still incomplete and includes genetic and environmental factors. CLL is one of the most familial of all cancers, yet common high-penetrance risk alleles have not been identified. Genome-wide association studies have identified many common variants with low relative risks, whereas exome-wide rare variant analysis has implicated ATM in CLL causation. Environmental factors have also been challenging to identify given the limited understanding of the relevant time period of exposure relative to diagnosis, and the inability to quantify past exposures. Agent Orange and glyphosate herbicides have perhaps the most data to support their role. CLL is preceded by a precursor condition called monoclonal B-cell lymphocytosis (MBL), which could therefore be considered a risk factor, but which itself is likely caused by the same risk factors that ultimately give rise to CLL. Although virtually all people with CLL have a preceding MBL phase, most people with MBL will not develop CLL.

A 10-year-old neutered male Maltese dog was presented for an investigation of lymphocytosis. The dog was up-to-date on vaccinations and deworming. Physical examination did not reveal any significant abnormalities. A complete blood cell count (CBC) showed mild leukocytosis with moderate lymphocytosis, basophilia, and moderate neutropenia, but no significant left shift or toxic change. Serum biochemistry and urinalysis were unremarkable. All performed tests for infectious agents common in this geographical region were negative. No significant abnormalities were found on abdominal ultrasound examination. Multiparametric flow cytometry of peripheral blood showed a CD8+ T-cell lymphocytosis, and PCR for antigen receptor rearrangement revealed a clonal expansion of the T-cell receptor gamma chain genes. A clinical diagnosis of chronic lymphocytic leukemia (CLL) was made, and follow-up was recommended. On Day 48 post-presentation, the CBC showed mild non-regenerative anemia (NRA), moderate leucocytosis due to moderate to marked lymphocytosis, basophilia, and a marked increase in hyposegmented neutrophils with mild toxic change in the absence of neutrophilia or neutropenia. Treatment with chlorambucil and prednisolone was initiated. On Days 87 and 197 post-presentation, the CBC showed mild NRA, with progressively decreasing numbers of hyposegmented neutrophils. The dog remained without clinical signs. Basophilia and probable pseudo-Pelger-Huët anomaly were possibly secondary to CLL. To the authors\' knowledge, this is the first report of these two hematologic conditions secondary to CLL in dogs. Recognition of a pseudo-Pelger-Huët anomaly is clinically relevant to avoid misinterpretation as a marked left shift due to severe inflammation and prevent unnecessary urgent therapeutic actions.

Persistent polyclonal B-cell lymphocytosis is a rare disease with chronic lymphocytosis of polyclonal origin, which is more frequent in mostly asymptomatic middle-aged female smokers. The hallmark of this entity is the presence of bilobed/binucleated B lymphocytes, which are polyclonal as demonstrated by immunophenotyping; an elevated IgM level is common. This disease shows, in most cases, an indolent course over many years and, although controversial, it may rarely convert to malignant lymphoma. In addition to smoking, a genetic predisposition for persistent polyclonal B-cell lymphocytosis is likely. Recurrent genetic aberrations have been described. The differential diagnosis includes non-Hodgkin\'s lymphoma and a clear distinction between both entities is of the utmost importance because treatment is generally not indicated in the former: instead, regular follow-up is recommended. The authors describe the case of a 46-year-old female smoker, who presented with chronic lymphocytosis, elevated IgM and circulating binucleated lymphocytes. Excluding lymphoma was important considering the unusual presentation with constitutional symptoms and splenomegaly.
A linfocitose policlonal persistente de células B é uma doença rara, caracterizada por linfocitose crónica policlonal, que ocorre mais frequentemente em mulheres fumadoras de meia-idade, que se apresentam assintomáticas ou com sintomas inespecíficos. A presença de linfócitos B binucleados é considerada a assinatura citomorfológica desta entidade. A imunofenotipagem comprova a sua origem policlonal, observando-se muitas vezes uma elevação da IgM sérica. É controverso se existe um risco aumentado de desenvolvimento de linfoma. A predisposição genética é também um fator de risco, além do tabagismo. Apesar da sua natureza policlonal, alterações genéticas recorrentes estão descritas. Na linfocitose policlonal persistente de células B a abordagem terapêutica consiste habitualmente numa vigilância regular, o que reforça a importância do seu reconhecimento. Os autores descrevem o caso de uma mulher de 46 anos, fumadora, com linfocitose crónica, IgM elevada e linfócitos binucleados. O diagnóstico diferencial com linfoma assumiu particular importância, considerando os sintomas constitucionais e esplenomegalia que apresentava.

UNASSIGNED: High-count monoclonal B-cell lymphocytosis (HCMBL) is a precursor condition to chronic lymphocytic leukemia (CLL). We have shown that among individuals with HCMBL, the CLL-International Prognostic Index (CLL-IPI) is prognostic for time-to-first therapy (TTFT). Little is known about the prognostic impact of somatically mutated genes among individuals with HCMBL. We sequenced DNA from 371 individuals with HCMBL using a targeted sequencing panel of 59 recurrently mutated genes in CLL to identify high-impact mutations. We compared the sequencing results with that of our treatment-naïve CLL cohort (N = 855) and used Cox regression to estimate hazard ratios and 95% confidence intervals (CIs) for associations with TTFT. The frequencies of any mutated genes were lower in HCMBL (52%) than CLL (70%). At 10 years, 37% of individuals with HCMBL with any mutated gene had progressed requiring treatment compared with 10% among individuals with HCMBL with no mutations; this led to 5.4-fold shorter TTFT (95% CI, 2.6-11.0) among HCMBL with any mutated gene vs none, independent of CLL-IPI. When considering individuals with low risk of progression according to CLL-IPI, those with HCMBL with any mutations had 4.3-fold shorter TTFT (95% CI, 1.6-11.8) vs those with none. Finally, when considering both CLL-IPI and any mutated gene status, we observed individuals with HCMBL who were high risk for both prognostic factors had worse prognosis than patients with low-risk CLL (ie, 5-year progression rate of 32% vs 21%, respectively). Among HCMBL, the frequency of somatically mutated genes at diagnosis is lower than that of CLL. Accounting for both the number of mutated genes and CLL-IPI can identify individuals with HCMBL with more aggressive clinical course.