BACKGROUND: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy.
METHODS: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity.
CONCLUSIONS: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free light chain (FLC) analysis. Alerted by two index cases with clinical impact due to failure of the FLC analysis to indicate a disease progression, we aimed to identify any clinical consequences due to known differences between FLC analysis methods. We applied two FLC analysis methods (Freelite Binding Site [FBS] and N-Latex Siemens [NLS]) on all patients with MM and monoclonal gammopathy of uncertain significance diagnosed/followed up at Södra Älvsborg Hematology Unit, from April to December 2022. From a total of 123 patients with malignant plasma cell disorder, we identified five cases (4.1%) where solely the FBS method, as opposed to NLS, urine and serum electrophoresis, could support diagnosis or detect progression. The consequences of this discrepancy included not only change of diagnosis or delayed therapy but also change of treatment. Our findings indicate that a stronger awareness of the potential weaknesses of different FLC methods is needed, which calls for a closer collaboration between clinical chemists and hematologists.

The diagnosis of multiple myeloma requires detection of paraproteinemia and confirmation of monoclonal bone marrow infiltration, along with signs of end-organ damage. Despite the increasing prevalence, serum paraproteinemia is not routinely measured. We examined the relationship between alterations in routine hematological parameters and the development of paraproteinemia in a case-control study. Data was retrieved from a laboratory database in the capital region of Denmark between 01/01/2012 and 31/12/2022. Patients were included if they had a test for paraproteinemia (n = 134,740) and at least one prior hematological parameter (white blood cells, hemoglobin and platelet count) with a minimum follow-up of 1 year.Between 96,999 and 103,590 patients were included in each of the three hematological groups. We found white blood cell count and the presence of paraproteinemia followed an inverse J-shaped curve, with the highest presence below 3 × 109/L and above > 9 × 109/L. The adjusted OR below and above the nadir of 4 × 109/L was 1.61 (95% CI 1.25; 2.08, p < 0.0001) and 1.03 (95% CI 1.03; 1.04, p < 0.0001). Hemoglobin levels were inversely associated the presence of paraproteinemia, with the highest association below 6 mmol/L with an OR of 1.30 (95% CI 1.28; 1.32, p < 0.0001) adjusted for age and gender. Platelet count followed a U-shaped curve with the highest association at < 100 × 109/L. The adjusted OR below and above the nadir of 250 × 109/L was 1.13 (95% CI 1.10; 1.17, p < 0.0001) and 1.10 (95% CI 1.08; 1.12, p < 0.0001) respectively. In conclusion, all three parameters showed significant association with later paraproteinemia.

Recent advances in the treatment of plasma cell disorders (PCDs) have provided a wealth of therapy alternatives and improved overall survival tremendously. Various types of PCDs are associated with kidney injury and end-stage kidney disease in a considerable number of patients. Kidney transplantation (KTx) is the best option for renal replacement therapy in select patients in terms of both quality of life parameters and overall survival. Even with modern therapies, all PCDs carry the risk of hematologic progression, whereas histologic recurrence and graft loss are other prevailing concerns in these patients. The risk of mortality is also higher in some of these disorders compared with KTx recipients who suffer from other causes of kidney disease. Unlike solid cancers, there is no well-defined \"waiting time\" after hematologic remission before proceeding to KTx. Thus, clinicians are usually reluctant to recommend KTx to patients who develop end-stage kidney disease due to PCDs. This review aims to provide the current evidence on KTx outcomes in patients with monoclonal gammopathy of renal significance and multiple myeloma. Although immunoglobulin light chain amyloidosis is a monoclonal gammopathy of renal significance subtype, KTx outcomes in this group are mentioned in another chapter of this issue.

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A 2-year-old neutered female Small Munsterlander dog was presented for an insect bite. Physical examination revealed a poor body condition, a peripheral lymphadenomegaly, and suspected splenomegaly. A complete blood count (Sysmex XN-V) revealed marked leukocytosis with lymphocytosis and abnormal dot plots. An abnormal monomorphic lymphoid population and marked rouleaux formation were noted on the blood smear. Lymph node aspirates contained an atypical bimorphic population of lymphocytes, either with a plasmacytoid or a blastic appearance. This double population was also found in the spleen, liver, bone marrow, tonsils, and other tissues. Peripheral blood and lymph node clonality assays revealed clonal BCR gene rearrangement. Flow cytometry revealed a mixed population of small-sized B-cells (CD79a+ CD21+ MHCII+) and medium-sized B-cells (CD79a+ CD21- MHCII-) in lymph nodes and a dominant population of small-sized mature B-cells (CD21+ MHCII+) in peripheral blood. Though normoproteinemic, serum protein electrophoresis revealed an increased α2-globulin fraction with an atypical restricted peak, identified as monoclonal IgM by immunofixation. Urine protein immunofixation revealed a Bence-Jones proteinuria. A diagnosis of Waldenström\'s macroglobulinemia was made. Chemotherapy was initiated, but the dog was euthanized 12 months after the initial presentation due to marked clinical degradation.

Cutaneous tuberculosis (CTB) and its paucibacillary forms are rare and difficult to diagnose, especially in immunocompromised patients with significant comorbidity. The aim of the study was to introduce the modern concept of the microbiome and diagnostic chain into clinical practice (patient-centered care) with the presentation of an atypical form of cutaneous tuberculosis with necrotizing non-healing ulcers leading to polymicrobial infection.
The study material included samples from sputum, broncho-alveolar lavage and skin ulcer, taken from a patient developing cutaneous tuberculosis. The microbiological investigation was performed, and identification of the isolates was carried out using genotyping and the matrix-assisted laser desorption ionization-time of flight mass spectrometry.
The immunocompromised patient with humoral abnormality (plasma cell dyscrasia) and severe paraproteinemia developed multiorgan tuberculosis. Although cutaneous manifestation preceded systemic and pulmonary symptoms (approximately half a year), the mycobacterial genotyping confirmed the same MTB strain existence in skin ulcers and the respiratory system. Therefore, the infectious chain: transmission, the portal of entry, and bacterial spreading in vivo, were unclear. Microbial diversity found in wound microbiota (among others Gordonia bronchialis, Corynebacterium tuberculostearicum, Staphylococcus haemolyticus, and Pseudomonas oryzihabitans) was associated with the spread of a skin lesion. The in vitro biofilm-forming capacity of strains isolated from the wound may represent the potential virulence of these strains. Thus, the role of polymicrobial biofilm may be crucial in ulcer formation and CTB manifestation.
Severe wound healing as a unique biofilm-forming niche should be tested for Mycobacterium (on species and strain levels) and coexisting microorganisms using a wide range of microbiological techniques. In immunodeficient patients with non-typical CTB presentation, the chain of transmission and MTB spread is still an open issue for further research.

BACKGROUND: Multiple Myeloma (MM) is a haematological malignancy with increasing global incidence. Diagnosis of MM should be initiated at the primary care level to achieve the best patient outcome. However, this can be delayed due to nonspecific presenting symptoms, such as back pain and fatigue.
OBJECTIVE: The aim of this study was to investigate if commonly requested blood tests could indicate MM in primary care and potentially lead to earlier diagnosis.
METHODS: This retrospective observational study involved an audit of clinical and laboratory data from 109 MM patients, including patients with Active MM (N = 53), Smouldering MM (N = 33), and Free light chain MM (N = 23).
RESULTS: Of the 16 potential biomarkers investigated, the most promising indicator for early detection of active MM and Smouldering MM was an increased Calculated Globulin (CG). The median CG for patients with active MM (50 g/L) was 78.6% higher than the healthy control group (28 g/L). Smouldering MM patients had a median CG value (38 g/L), which was 35.7% higher than the control group. Of interest, the median CG result was only 16.7% higher in the control group than in the free light chain MM group, suggesting CG would not be as effective at detecting this subtype.
CONCLUSIONS: CG is derived from Total Protein and Albumin data, which are commonly measured in routine liver function profiles, thus there is no additional test or cost requirement. Based on these data, CG has potential as a clinical biomarker to support early detection of MM at the primary care level and allow for appropriate targeted investigations.

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