Waldenström's macroglobulinemia - clinical symptoms and review of therapy yesterday, today and tomorrow.

BACKGROUND: Waldenström macroglobulinemia (WM) is a lymphoplasmocytic lymphoma with immunoglobulin M monoclonal protein. The incidence of this disease is very low (0.4/100,000), so that this disease can be regarded as an orphan's disease. It means that new drugs are often tested and registered for more frequent diseases. PURPOSE: In this review we will focus on the efficacy of the new drugs for WM. RESULTS: The current treatment options for symptomatic WM patients include alkylating agent cyclophosphamide and anti-CD20 monoclonal antibodies. Therapy with rituximab and bendamustin resulted in longer therapeutic response then therapy with rituximab, cyclophosphamide and dexamethasone. Many drugs, used in multiple myeloma (MM), shoved promising results in WM patients. Bortezomib is effective in WM, but its neurotoxicity is higher in WM than in MM patients. Therefore, new proteasome inhibitors, carfilzomib and ixazomib, are better tolerated as documented in several studies. New types of antiCD20 antibody (obinutuzumab) can be used in patients with rituximab intolerance. in five of our patients with WM, obinutuzumab and bendamustin reached deeper responses than therapies administered in previous lines of therapy. Oral Bruton tyrosine kinase (BTK) inhibitor ibrutinib alone and in combination with rituximab have extended the treatment options for WM patients. New BTK inhibitors (e. g. acalabrutinib, zanubrutinib, and vecabrutinib) were tested and their lower toxicity (atrial fibrillation) was documented. Moreover, the BCL2 inhibitor venetoclax is newly tested. CONCLUSION: New antiCD20 antibody (obinutuzumab) is of advantage in patients with WM with rituximab intolerance as well as bendamustin and new proteasome inhibitors (ixazomib and carfilzomib) or new BTK inhibitors with lower cardiotoxicity. Many of the abovementioned drugs do not have official registration for WM and can be administrated with the consent of the health care provider only. Thus, this work brings evidence of their efficacy.

Therapy of Castleman's disease with siltuximab - case report and review of literature.

BACKGROUND: Idiopathic multicentric Castleman disease (iMCD) is characterized by constitutional symptoms, enlarged lymph nodes and laboratory test abnormalities, which are primarily related to the overproduction of interleukin-6 (IL-6). This form (iMCD) was treated earlier with cytostatics used for lymphoma, later with bio-logic therapy as rituximab, immunodulatory drugs and proteasome inhibitors, and in the last years with an anti-IL-6 antibody, siltuximab. Siltuximab is a human-mouse chimeric immunoglobulin G1k monoclonal antibody against human IL-6 approved in the European Union for the treatment of iMCD. In view of the limited treatment options for iMCD, this case report aimed to evaluate the efficacy and safety of siltuximab in the management of this condition. CASE: We describe a young woman with iMCD diagnosed at the age of 25 years. For first line treatment, rituximab and dexamethasone were used without any cytostatic because the patient wished to give birth to a healthy child in the future. However, the response after this first line therapy was short. In addition, after 3 years from the start of rituximab + dexamethasone therapy, it was necessary to administer treatment for the relapse of iMCD. We decided for siltuximab in this young woman, still aged < 30 years, and started administration of siltuximab in 3-week intervals. RESULTS: After administration of first two infusions of siltuximab, all inflammatory markers returned to normal value. Moreover, serum hemoglobin and albumin levels as well as C-reactive protein normalized after the first two administrations of siltuximab. The clinical response continue, siltuximab is still administered in 3-week intervals. PET/CT with fluorodeoxyglucose confirmed a very good anatomic and metabolic response to the treatment. Siltuximab demonstrated a favorable safety profile, and the prolonged treatment was well tolerated. CONCLUSION: This result is encouraging and demonstrates the potential of siltuximab as treatment of CD. As earlier published, this case confirms that significantly elevated inflammatory markers in a patient with CD predict a good response to siltuximab.

Gamma-heavy chain disease.

BACKGROUND: Gamma-heavy chain disease is a rare disease, described so far in approximately 150 cases. The aim of this work was laboratory dia-gnostics of immunoglobulin heavy chain disease. MATERIALS AND METHODS: A 60-year-old patient was referred to the University Hospital in Ostrava for suspected marginal zone lymphoma from gastric bio-psy. Staging examinations including bone marrow trepanobio-psy and PET/CT were added; special examinations required serum protein electrophoresis, immunofixation electrophoresis, determination of polyclonal immunoglobulins, free light chains, and immunoglobulin heavy/light chain pairs. Isoelectric focusing in agarose gel followed by affinity immunoblotting and SDS electrophoresis was added due to unclear findings. RESULTS: 0.1 % of plasma cells were found in the bone marrow, of which 87 % were clonal (pathological) plasma cells, followed by the cyt cytotype LAMBDA + CD38 + CD138 + CD45 + CD19 + CD56- CD27 + CD81- CD117-. Monoclonal heavy chains were found in the patients serum. No monoclonal immunoglobulin heavy or light chains were detected in urine. The PET/CT examination showed generalized lymphadenopathy, splenomegaly and inhomogeneous accumulation of fluorodeoxyglucose in axillary and appendicular skeleton, but without the presence of typical osteolytic lesions. CONCLUSION: Monoclonal heavy chains of immunoglobulins are a rare disease. In contrast to the detection of a complete paraprotein molecule, additional methods must be used to confirm them. The finding of monoclonal heavy chain gamma in the serum of the study patient is related to the presence of marginal zone lymphoma, which was proven from a gastric bio-psy. The study was supported by the project of MH CZ - DRO - FNOs /2017 (Biobank in Teaching Hospital Ostrava) The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

Chemopreventive effects of combination of honokiol and magnolol with α-santalol on skin cancer developments.

α-Santalol is active component of sandalwood oil and has been shown to have chemopreventive effects against chemically and UVB-induced skin cancer development in mice. α-Santalol is also shown to have skin permeation enhancing effects. Honokiol and magnolol isolated from Magnolia officinalis bark extract have also been shown to have chemopreventive effects against chemically and UVB-induced skin cancer in mice. This study was conducted to investigate the combination effects of α-santalol, honokiol and magnolol to study any additive/synergistic effects to lower the doses required for chemoprevention. Pretreatment of combinations of α-santalol with honokiol and magnolol significantly decreased tumor multiplicity upto 75% than control, α-santalol, honokiol and magnolol alone in SKH-1 mice. Combination of α-santalol with honokiol and magnolol also decreased cell viability, proliferation, and enhanced apotosis in comparison to α-santalol, honokiol and magnolol alone in Human epidrmoid carcinoma A431 cells. Overall, the results of present study indicated combinations of α-santalol with honokiol and magnolol could provide chemoprevention of skin cancer at lower doses than given alone.

Cerebrospinal fluid cytologic findings in multiple sclerosis. A comparison between patient subgroups.

OBJECTIVE: To compare cytologic findings in cerebrospinal fluid (CSF) in various subgroups of multiple sclerosis (MS) patients. STUDY DESIGN: CSF from 77 patients with clinically definitive or probable MS was examined by means of qualitative cytology. After the cell count was determined in a Fuchs-Rosenthal chamber, slides were prepared by the cytosedimentation method and stained with May-Grünwald-Giemsa stain and oil red O and, whenever possible, with Papanicolaou stain and toluidine blue. In addition to the differential cell count, the lymphocyte/monocyte ratio, percentage of activated forms in the lymphocytic and monocytic series, presence and percentage of lymphoplasmacytes and mature plasma cells, presence of lipophages, lymphophages and presence of mitotic figures were evaluated. RESULTS: The following statistically significant differences were found between the various MS subgroups: (1) higher prevalence of mitotic figures in the primary progressive MS subgroup; (2) higher prevalence of foam cells and lymphophages and lower prevalence of CSF pleocytosis in more severely disabled patients; (3) lower cell count, lower prevalence of CSF pleocytosis, lower lymphocyte/monocyte ratio and lower prevalence of lymphoplasmacytes in treated patients; and (4) higher prevalence of mature plasma cells and lipophages in MS patients with disease of longer duration. CONCLUSION: The differences observed in the various MS subgroups may reflect certain aspects of MS pathogenesis. Qualitative CSF cytology may therefore be useful for both clinicians and neuroimmunologists. Qualitative cytology of CSF is an important diagnostic method that should never be omitted from an examination of CSF from patients with MS.

Scrotal cestodiasis in a dog.

Scrotal cestodiasis was diagnosed from a surgical biopsy specimen from an 8-year-old Miniature Poodle. Peritoneal cestodiasis with secondary scrotal cestodiasis was suspected and could be explained by migration of the parasite along the vaginal tunics. Subsequent necropsy confirmed severe peritoneal cestodiasis due to Mesocestoides sp. It appears that scrotal cestodiasis may be an early indicator of peritoneal cestodiasis in male dogs and diagnostic pathologists and clinicians should be aware of this condition.

Intracranial squamous cell carcinoma in a cow.

An exophthalmic right eye was surgically removed from a nine year old Holstein cow. Subsequent post mortem examination revealed a large intracranial mass at the base of the brain which was diagnosed as a squamous cell carcinoma. The orbital and sphenoid bones were intact and it is believed that the neoplasm entered the cranial cavity from the orbit via the foramen orbitorotundum. Both intracranial squamous cell carcinoma and extension of orbital neoplasia through foramina are rare.

Encephalitozoonosis in squirrel monkeys (Saimiri sciureus).

Twenty-two cases of naturally occurring encephalitozoonosis in squirrel monkeys are reported from breeding colonies of the Delta Regional Primate Research Center, Covington, La. Characteristic foci of granulomatous inflammation and organisms were demonstrated in brains, kidneys, lungs, adrenals, and livers. Vasculitis and perivasculitis were also common lesions in several organs. At least seven cases were congenital while ten others occurred in monkeys less than nine months old. Granulomatous placentitis, previously unreported in any species due to Encephalitozoon cuniculi, was present in one monkey.