AGGRESSIVE B CELL LYMPHOMA WITH METASTATIC SPINAL CORD COMPRESSION: TREAT THE PATIENT, NOT THE DISEASE.

INTRODUCTION: The management of malignant spinal cord compression (mSCC) is a demanding task. The main challenges of mSCC include various manifestations and unpredictable outcomes with indiscriminate treatment recommendations. Because of attendant urgency with potentially devastating health consequences, the SCC is an emotionally disturbing experience whose management could take an impulsive rather than rational approach. The treatment strategy is particularly problematic when mSCC is caused by a malignant lymphoma with its protean attributes. CASE REPORT: A 68-year-old female presented with generalized body pain and weight loss. Imaging studies revealed a vast bulk of the disease involving lymph nodes, spleen, visceral organs, musculature, marrow, and bones including vertebrae with extension into the spinal canal. A biopsy of the chest wall mass showed high-grade diffuse large B cell lymphoma. A magnetic resonance imaging (MRI) of the spine demonstrated diffuse marrow replacement by the tumor of the thoracic and lumbar spine with compression of the cord. The prompt treatment with corticosteroids and immunochemotherapy (ICT) was recommended, but the patient elected to seek a second opinion. After two doses of radiation therapy (RT), the patient's general condition rapidly deteriorated and she was hospitalized for systemic ICT. Despite the treatment, her condition continued to deteriorate, and she died three weeks after the presentation. CONCLUSION: The presented case demonstrates some hitherto unaddressed challenges in evaluation and treatment of mSCC caused by aggressive non-Hodgkin lymphoma (LSSC). The case scrutinizes the role of MRI in uncommon clinical situations. The case has also exposed some ethical issues associated with the proper management of LSCC.

The role of staging in multiple myeloma.

INTRODUCTION: The importance of cancer staging is determined by how accurately it can predict prognosis, and how useful it is for treatment decisions. Compared to other malignancies, multiple myeloma (MM) staging proved more challenging because of unreliable prognostic factors and wide-ranging life expectancy. As traditional MM staging continues to evolve, it requires reassessment of its prognostic and predictive value. AREAS COVERED: The studies that included prognostic and predictive value of MM stages from 1975 through 2023 were selected for this review using PubMed, MEDLINE platforms. The history and evolution of MM staging are revisited, including its role in predicting survival, treatment planning and potential practical implications for the future. The role of MM staging for oncological practice and patient counseling is discussed. EXPERT OPINION: The utility of the traditional MM staging remains unsatisfactory because it lacks a strong connection with the disease biology, prognosis or treatment planning. Additionally, it demonstrates a modest value for patient counseling because individual prognosis is subject to under- or overestimation, and the median survival or survival rates are difficult concepts to grasp. Although the role of MM stages may change in the future, the current research upholds the notion that MM staging benefits more medical research and clinical trials than oncological practice.

Can Gilbert's syndrome mitigate chronic lymphocytic leukemia?

The study links two intriguing observations about chronic lymphocytic leukemia and Gilbert's syndrome - the oxidative stress affecting the former, and the anti-oxidative effects of the latter. Our pilot study showed that compared to the general CLL population, the GS/CLL cohort less commonly required therapy and demonstrated a reduced CLL-related mortality. Our findings prompt a speculation that elevated bilirubin in GS could hypothetically attenuate the oxidative stress thereby exerting a safeguarding effect on leukemia pathogenesis. We believe that this hypothesis-generating study could open new avenues for exploring oxidative stress as a potential pathogenetic and, hypothetically, therapeutic target for mitigating CLL.

Atypical "accelerated" chronic lymphocytic leukemia with abnormal lymphocyte chromatin clumping, bone involvement, and exceptional response to Imbruvica.

BACKGROUND: The "accelerated" chronic lymphocytic leukemia (aCLL) is a relatively rare form of CLL progression. The expanded proliferation centers in aCLL have been associated with adverse prognostic features and propensity to more aggressive behavior with shorter survival. CASE: An atypical case of aCLL with distinct features is described. A 66-year-old female presented with a marrow replacing process associated with multiple osseous metastases and trivial lymphadenopathy. Bone biopsy revealed an unspecified low-grade B cell lymphoproliferative disorder that demonstrated a suboptimal response to standard chemotherapy. Subsequent lymph node biopsy demonstrated findings consisted with aCLL. The distinguishing features of the case were, in addition to bone involvement, the lagging peripheral lymphocytosis and a striking pattern of the chromatin clumping with a prominent "shattered" appearance reminiscent of Pelger-Huet-like dysplastic anomaly. A targeted next-generation sequencing (NGS) assay detected pathogenic mutations in TP53 and SF3B1. In contrast to chemotherapy, the case demonstrated an excellent response to imbruvica. CONCLUSION: The noted peculiarities could potentially distinguish this case as a novel, rare variant of aCLL.

Bilateral auricular lymphoplasmacytic lymphoma: barely mere coincidence.

We describe the first case of LPL simultaneously involving both auricles. Affected ears were the first manifestation of the disease that led to the diagnosis. The lack of appreciable systemic disease allowed sparing the patient from immunochemotherapy. Radiation therapy was used as a single modality and secured a stable remission. A putative pathogenesis of the paired auricular lymphoma is discussed and a literature review presented. While the role of genetic predisposition in our patient was uncertain, we postulate that symmetric ear lymphoma could have been caused by a combined effect of the homing of malignant lymphocytes whose localized growth was triggered by the hazardous environmental exposure.

Mean corpuscular volume, hematocrit and polycythemia.

Mean corpuscular volume (MCV) as a measure of the size of red blood cells (RBCs) has been pivotal in the diagnosis and morphologic classification of anemias for over a century. Despite its ubiquitous use and time-honored diagnostic value, one essential attribute of MCV has remained under the radar. It has been long underappreciated that the size of RBC correlates with the amount of hemoglobin (Hb) that it accommodates and, therefore, is an important determining factor of the total Hb level. By scrutinizing this basic principle, it has become possible to uncover a hitherto obscured relationship between MCV, hematocrit (Hct) and RBCs described as a dynamic equilibrium. This principle is shown to be invaluable in interpreting RBC parameters, particularly for the evaluation of patients with polycythemia.

Smoldering multiple myeloma 40 years later: a story of unintended disease.

Introduction: Smoldering multiple myeloma (SMM) is a clonal plasma cell (PC) disorder considered a prelude to MM due to its greater malignant potential compared to monoclonal gammopathy of undetermined significance (MGUS). Despite tectonic changes in the SMM landscape that occurred since it was first distinguished four decades ago, SMM continues to represent a complex and controversial entity causing a great deal of diagnostic and management turmoil.Areas covered: Author addresses increasingly complicated, ambiguous, as well as some overlooked and misjudged aspects of SMM such as the disease identity, relationship to its counterparts, MGUS and overt MM, its niche in the modern classification of monoclonal gammopathies and management. The PubMed search (1980-2020) was conducted and the current NCCN guidelines reviewed in reference to the diagnosis and treatment of smoldering multiple myeloma.Expert opinion: A plethora of clinical and biological evidence points to SMM as a source of the ongoing and expanding uncertainty of this condition and calls into question its authenticity as a discrete entity. Until comprehensive testing can predict the progression of pre-myeloma conditions with the utmost precision, attempts at preemptive treatments will fail to answer the basic question of who will benefit from the early treatment and who will not.

Elevated Hemoglobin and Macrocytosis: A Neglected Association to Become a Diagnostic Tool (A Case Report).

INTRODUCTION: The landmark value of mean corpuscular volume (MCV) in the diagnosis and classification of anemias has been established more than a century ago. In contrast, the importance of MCV assessment in patients with elevated hemoglobin and hematocrit is not nearly as appreciated. CASE PRESENTATION: This case describes a patient who exhibited long-standing macrocytosis (elevated MCV) that contributed to elevated hemoglobin and hematocrit levels thus mimicking a diagnosis of polycythemia vera. CONCLUSION: The case demonstrates that discounting the MCV effect on hemoglobin/hematocrit levels can lead to potential errors in interpretation of blood tests and misdiagnosis.

An upsurge of the serum free light chains as a possible missing link in tumour lysis syndrome in multiple myeloma.

Multiple myeloma (MM) is a slow-growing malignancy characterized by a low proliferation rate of plasma cells and a relatively rare incidence of tumour lysis syndrome (TLS). Three myeloma patients developed TLS following cytotoxic therapy (two after radiation treatment) that was associated with an abrupt increase of serum free light chains (FLC). All three patients demonstrated extramedullary plasmacytomas that exhibited aggressive features compared to the original myeloma. The findings suggested that an abrupt liberation (rather than slow secretion) of FLC from myeloma cells may trigger a fulminant cast nephropathy and present an unrecognized risk factor and potentially aggravating component of TLS.

A Tale of Two Immunodeficiencies: A Case of Multiple Myeloma Associated with Profound Immune Defect Mimicking Common Variable Immunodeficiency Syndrome.

INTRODUCTION: Multiple myeloma (MM) is a clonal plasma cell disorder commonly associated with secondary immune deficiency. By contrast, common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low serum levels of immunoglobulins (IgG, IgA, and/or IgM) and inability to produce specific protective antibodies in response to infections and immunizations. Besides a defective immune system and susceptibility to infections, CVID is associated with autoimmune disorders, gastrointestinal tract inflammation, granulomatous disease, and malignancies. Although MM and CVID both manifest an abnormal immune system homeostasis, the pathogenesis of the immune defect is distinctly different: Quantitative deficiency of the normal plasma cells in the former and qualitative defect in plasma cell maturation in the latter. CASE PRESENTATION: An unusual case of MM associated with profound immunodeficiency mimicking CVID occurred in a 51-year-old man with a history of numerous bacterial infections and low γ-globulin levels. DISCUSSION: A hypothetical connection between MM and CVID is discussed. Patients with MM who have an unusually high burden of infections and profound immune deficit persisting even after successful myeloma therapy merit recognition as a distinct cohort that warrants heightened attention from clinicians and scientists.

Unrecognized Value of Carcinoembryonic Antigen in Recurrent Rectal and Sigmoid Colon Cancer: Case Series.

INTRODUCTION: Carcinoembryonic antigen (CEA) surveillance is recommended in patients with colorectal cancer for detection of potentially resectable metastases. In patients with appropriate symptoms, a highly increased CEA concentration (> 5 times the upper limit of normal) is considered strongly suggestive of cancer. Despite the recognized value, the test is neither absolutely sensitive nor specific for recurrent cancer. Generally, a greater diagnostic value has been assigned to elevated CEA levels, most commonly greater than 5 ng/mL. Fluctuations within the established normal CEA range are not customarily analyzed. CASE PRESENTATIONS: We report here on 11 patients (8 women, 3 men) who, during the postoperative follow-up period, received a diagnosis of recurrent cancer despite their CEA levels exhibiting very subtle increases. Our cohort shared several similar characteristics such as a nonsmoking status, younger age (median, 52 years at initial diagnosis), and exclusive localization of the cancer to the rectosigmoid region. DISCUSSION: This important clinical observation may expand a prognostic value of CEA in a certain category of patients with colorectal cancer.

Phase II trial of irinotecan and carboplatin for extensive or relapsed small-cell lung cancer.

PURPOSE: The regimens of weekly irinotecan with platinum have been used for treatment of metastatic small-cell lung cancer (SCLC). We conducted a multi-institution phase II trial to evaluate a novel 21-day schedule of irinotecan and carboplatin in patients with relapsed or extensive SCLC. PATIENTS AND METHODS: Eighty patients were enrolled with the following characteristics: 39 male patients, 41 female patients; median age, 65 years; and Zubrod performance status, 0 to 1 in 85% and 2 in 15% of patients. Dosing schemas were based on the maximum-tolerated dose derived in a previous phase I study. Chemotherapy-naive patients with extensive SCLC were treated with irinotecan 200 mg/m(2) and carboplatin area under the curve (AUC) of 5 (arm A). Patients, who had previously been treated with chemotherapy and had relapsed disease received irinotecan 150 mg/m(2) and carboplatin AUC of 5 (arm B). In each study arm, the treatment was given every 21 days for up to six cycles. RESULTS: The most common grade 3 to 4 toxicities included neutropenia (54%), thrombocytopenia (22%), anemia (13%), diarrhea (22%), and nausea/emesis (11%) in both study arms. There were three treatment-related deaths owing to neutropenic sepsis. Among 72 assessable patients, response rates of 65% and 50% were observed, respectively, for arm A and arm B. The median survival for both study arms was identical at 10 months (95% CI, 6 to 14 months). A response rate of 65% was observed in the intracranial disease of 14 patients with known brain metastases. CONCLUSION: This 21-day regimen of irinotecan and carboplatin seems promising for the treatment of relapsed SCLC.