Treatment and Response Evaluation Challenges in a Pregnant Woman With B-Cell Lymphoblastic Leukemia and Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is a cancer predisposing syndrome caused by pathogenic germline TP53 gene mutations with important therapeutic and prognostic implications for many types of cancer. A small proportion of LFS patients develop B-cell lymphoblastic leukemia (B-ALL) in adult years. Standard treatment often proves inadequate, but immunotherapy has provided new treatment options. The current case report presents a pregnant woman with LFS and newly diagnosed B-ALL with hypodiploidy developed after treatment for early-onset breast cancer. We describe the treatment course, treatment-related complications and provide laboratory data crucial for evaluating and modifying treatment for this difficult clinical case. Our findings support the need for close collaboration between clinicians and experts on immunophenotyping. Through our report, we show that immunotherapy is feasible in patients with LFS and B-ALL, despite a poor initial response to induction therapy.

Case Report: Polyvinylpyrrolidone deposition disease from repeated injection of opioid substitution drugs: report of a case with a fatal outcome.

Background: Intravenous injection of oral opioid substitution drugs (OSD) is widespread among injecting drug users. Several OSDs contain the polymer polyvinylpyrrolidone (PVP) as an excipient. Parenterally administered PVP of high molecular weight may accumulate in tissues and organs. This phenomenon was first described in the 1950s, when PVP was utilised in medication for parenteral use. We report a case of an opioid-addicted patient with extensive PVP-deposition caused by repeated injections of OSDs. Case presentation: A 30-year-old male drug addicted patient in opioid substitution therapy (OST) was repeatedly referred to his local hospital in a poor general condition. Work-up revealed severe normocytic anaemia, renal insufficiency, pancreas insufficiency and pathological fractures. Biopsies from fractured bones, bone marrow and gastric mucosa showed extensive infiltrates of histiocytes with intracytoplasmic vacuoles. Vacuole content stained slightly bluish in hematoxylin and eosin stain, red in Congo red stain and black in periodic acid methenamine silver stain. The morphological appearance and staining properties were in accordance with the diagnosis of PVP deposition. The patient had been injecting both buprenorphine tablets and a specific methadone syrup for several years. The methadone syrup contained large amounts of high molecular weight PVP, making it the most likely cause of the deposition. His health quickly deteriorated and he died, impaired by multi-organ failure and cachexia, five years after the first diagnosis of PVP-deposition. The autopsy revealed extensive PVP-deposition in all sampled organs and tissues. Conclusions: Histological investigation and the correct identification of PVP in the biopsies led to the discovery of a severe adverse effect from long-standing misuse of a drug. The disseminated PVP deposition likely contributed to multi-organ dysfunction and cachexia with a fatal outcome. The deposited PVP likely originated from repeated injections of a certain methadone syrup.

Polyvinylpyrrolidone deposition disease in patients with intravenous opioid use: a case series.

The polymer polyvinylpyrrolidone (PVP) is an excipient widely used in prescription drugs. Depending on the molecular weight (MW), parenterally administered PVP may accumulate in various tissues. Consequently, moderate and high MW PVP have only been used in oral preparations since the late 1970s. Surprisingly, starting in 2009, pathology departments in Norway received biopsies revealing PVP deposition, all from patients with a history of intravenous drug use. We identified 13 patients with PVP deposition and re-evaluated 31 biopsies and two autopsies. Common indications for biopsy were renal insufficiency, anemia, pathological fractures, and abdominal complaints. We observed PVP deposits in all biopsies (kidney, hematopoietic bone marrow, bone, gastrointestinal tract, lymph node, and skin) and all sampled tissue from the autopsies. Overall, the clinical findings could be related to PVP deposits in the biopsies. In the most seriously affected patients, PVP deposition caused severe organ dysfunction and contributed to the fatal outcomes of two patients. All patients except for one were prescribed opioid substitution drugs (OSDs), and most of the patients admitted to having injected such medications. Several OSDs contain PVP. One methadone formulation that was marketed in Norway from 2007 to 2014 contained large amounts of very high MW PVP, making it the most likely source of PVP deposition. Although the presumed source of PVP in these patients has now been withdrawn from the market, pathologists should be aware of PVP deposits when evaluating biopsies from this patient group.

Immunoglobulin-Storing Histiocytosis: A Case Based Systemic Review.

Crystal-storing histiocytosis (CSH) is a rare event in disorders associated with monoclonal gammopathy and is mostly associated with the accumulation of immunoglobulins (Igs) in the cytoplasm of histiocytes. In this article, we present a case of a 75-year-old female with IgG kappa monoclonal gammopathy of undetermined significance (MGUS) and signs of a non-crystallized version of immunoglobulin-storing histiocytosis (IgSH) in a vertebra corpus. Furthermore, we performed a literature review based on all cases of storing histiocytosis identified by literature search between 1987 and 2020 and identified 140 cases in total. The median age at diagnosis was 60 years (range 18-91), with an equal sex distribution (51% men). The majority of the patients had an underlying neoplastic B-cell disorder, most often multiple myeloma (MM), MGUS, or lymphoplasmacytic lymphoma (LPL). The main affected organ systems or tissue sites were bone (n = 52), followed by head and neck (n = 31), kidney (n = 23), lung (n = 20), and gastrointestinal (GI)-tract (n = 18). IgG was the main immunoglobulin class involved, and most cases were associated with kappa light chain expression. We conclude that IgSH is a rare disease entity but should be considered with unusual findings in several organ systems associated with monoclonal gammopathy, especially with kappa light chain expression.

Severe nephritis as initial sign of Waldenström's macroglobulinemia.

Waldenström's macroglobulinemia (WM), characterized with monoclonal immunoglobulins of type M and lymphoplasmacytic lymphoma, is a rare clonal Bcell disorder. WM usually present as an indolent lymphoma, and renal involvement is, in contrast to multiple myeloma, very rarely seen. We present a patient presenting with severe nephritis and nephrotic range proteinuria of more than 9 g/day as initial manifestations of WM. Furthermore, we discuss diagnostic and therapeutic approaches for this rare manifestation of the disease, in the light of recent research and treatment recommendations.

Philadelphia chromosome positive AML arising from JAK2-positive myelofibrosis.

BACKGROUND: A feature of myeloproliferative neoplasia is transforming to more aggressive and malignant myeloid neoplasia, including acute myeloid leukemia. Different pathogenesis mechanisms participate in transformation, including transformation of existing potential preleukemic clones, since JAK2-mutant myeloproliferative neoplasms often transform to JAK2 wild-type acute myeloid leukemia. CASE PRESENTATION: Here, we present an 80 year old man with a JAK2-V617F mutant primary myelofibrosis. After 10 months the disease transform into a Philadelphia chromosome positive acute myeloid leukemia, detecting the cytogenetic aberration; t(9;22)(q34;q22) encoding the rare BCR-ABL1 fusion gene; e6a2. The patient had treatment response to tyrosine kinases, illustrating the potential benefits of such approach in treating these patients subset. CONCLUSION: The case illustrates the potential of leukemic transformation to Philadelphia chromosome positive myeloid malignancies from potential existing preleukemic clones, and the awareness of such an evolution among patients with myeloproliferative neoplasms. Tyrosine kinases have potential effect also in patients presenting without chronic myeloid leukemia and with rare BCR-ABL1 fusion transcripts, and should probably be a part of the treatment approach.

A randomised trial of endobronchial ultrasound guided sampling in peripheral lung lesions.

AIM: The aim of the study was to evaluate endobronchial ultrasound (EBUS) for peripheral lung lesions and to find the most cost effective combination of sampling techniques. MATERIALS: 264 patients with lesions suspicious of malignancy were recruited in Bergen and Aalesund, Norway from 2005 to 2008. METHODS: The study was a prospective randomised cohort study. EBUS was performed with a 1.7 mm rotating probe. X-ray fluoroscopy was used in both arms. The different sampling techniques were evaluated in a cost-effectiveness analysis. RESULTS: The detection rate for cancer was 36% in the EBUS group, 44% in the non-EBUS group (ns). Lesions below 3 cm and lesions assumed difficult to reach had significant lower detection rates in the EBUS group. Lesions visualised by EBUS had a higher detection rate for cancer than lesions not visualised by EBUS (62% vs. 19%, p<0.01). The cost of one additional positive sample was 1211 euro when brushing was added to biopsy. It was not cost effective to add washing or TBNA. CONCLUSION: EBUS did not increase the detection rate for cancer in peripheral lung lesions when bronchoscopy was performed by bronchoscopists at all levels of expertise. Biopsy and brushing was the most cost effective combination of sampling techniques.

Cost minimization analysis for combinations of sampling techniques in bronchoscopy of endobronchial lesions.

BACKGROUND: The choice of sampling techniques in bronchoscopy with sampling from a visible lesion will depend on the expected diagnostic yields and the costs of the sampling techniques. AIMS: The aim of this study was to determine the most economical combination of sampling techniques when approaching endobronchial visible lesions. METHODS: A cost minimization analysis was performed. All bronchoscopies from 2003 and 2004 at Haukeland university hospital, Bergen, Norway, were reviewed retrospectively for diagnostic yields. 162 patients with endobronchial disease were included. Potential sampling techniques used were biopsy, brushing, endobronchial needle aspiration (EBNA) and washings. Costs were estimated based on registration of equipment costs and personnel costs. Sensitivity analyses were performed to determine threshold values. RESULTS: The combination of biopsy, brushing and EBNA was the most economical strategy with an average cost of Euro 893 (95% CI: 657, 1336). The cost of brushing had to be below Euro 83 and it had to increase the diagnostic yield more than 2.2%, for biopsy and brushing to be more economical than biopsy alone. The combination of biopsy, brushing and EBNA was more economical than biopsy and brushing when the cost of EBNA was below Euro 205 and the increase in diagnostic yield was above 5.2%. CONCLUSION: In the current study setting, biopsy, brushing and EBNA was the most economical combination of sampling techniques for endobronchial visible lesions.

Predictors of diagnostic yield in bronchoscopy: a retrospective cohort study comparing different combinations of sampling techniques.

BACKGROUND: The reported diagnostic yield from bronchoscopies in patients with lung cancer varies greatly. The optimal combination of sampling techniques has not been finally established. The objectives of this study were to find the predictors of diagnostic yield in bronchoscopy and to evaluate different combinations of sampling techniques. METHODS: All bronchoscopies performed on suspicion of lung malignancy in 2003 and 2004 were reviewed, and 363 patients with proven malignant lung disease were included in the study. Sampling techniques performed were biopsy, transbronchial needle aspiration (TBNA), brushing, small volume lavage (SVL), and aspiration of fluid from the entire procedure. Logistic regression analyses were adjusted for sex, age, endobronchial visibility, localization (lobe), distance from carina, and tumor size. RESULTS: The adjusted odds ratios (OR) with 95% confidence intervals (CI) for a positive diagnostic yield through all procedures were 17.0 (8.5-34.0) for endobronchial lesions, and 2.6 (1.3-5.2) for constriction/compression, compared to non-visible lesions; 3.8 (1.3-10.7) for lesions > 4 cm, 6.7 (2.1-21.8) for lesions 3-4 cm, and 2.5 (0.8-7.9) for lesions 2-3 cm compared with lesions <= 2 cm. The combined diagnostic yield of biopsy and TBNA was 83.7% for endobronchial lesions and 54.2% for the combined group without visible lesions. This was superior to either technique alone, whereas additional brushing, SVL, and aspiration did not significantly increase the diagnostic yield. CONCLUSION: In patients with malignant lung disease, visible lesions and larger tumor size were significant predictors of higher diagnostic yield, after adjustment for sex, age, distance from carina, side and lobe. The combined diagnostic yield of biopsy and TBNA was significant higher than with either technique alone.