Reduced Corticosteroid Exposure Is Safe and Does Not Reduce Disease Control among Hodgkin Lymphoma Patients Treated with Escalated BEACOPP (eBEACOPP).

Background and Objectives: eBEACOPP is the most effective chemotherapy regimen for younger patients with early unfavorable (EU) and advanced-stage (AS) Hodgkin lymphoma (HL), albeit with significant toxicities. The 14-day/cycle prednisone course contributes to side effects, including osteoarticular events like avascular bone necrosis (AVN). Our center has been using eBEACOPP since 2009 for AS and 2014 for EU patients. In 2016, we reduced prednisone treatment to 7-10 days to lessen AVN risk. We analyzed the effects of this approach. Materials and Methods: We retrospectively collected data on patients who received at least two cycles of eBEACOPP for first-line HL treatment. Results: A total of 162 patients (33 EU, 129 AS) were included. Their median age was 31 (range 19-59 years), and 88 were males. A total of 94 patients received full corticosteroid courses, and 68 received reduced corticosteroid courses. The overall response rate (ORR) was 98%. Different corticosteroid dosings had no significant effect on ORR, febrile neutropenia episodes, or hospital admissions. After a median follow-up (mFU) of 58 months, the 5yPFS for the entire cohort was 98% vs. 95% for the standard course vs. the short corticosteroids course, respectively (p = 0.37), while the 5yOS was 98% vs. 99% for the standard course vs. short corticosteroids course, respectively (p = 0.87). In AS patients intended to be treated with six eBEACOPP cycles, 5yPFS and 5yOS were 100% vs. 97% and 100% vs. 99% for standard vs. short corticosteroid courses, respectively (p = 0.56 and p = 0.17). In EU patients, 5yPFS was 97% (standard) vs. 95% (short) (p = 0.98) and 5yOS 100% vs. 93.3% (p = 0.87). Osteoarticular events were numerically lower in patients receiving the shorter prednisone course, both in the whole cohort and in the subgroup of patients treated with six cycles of eBEACOPP, but this difference failed to reach statistical significance. Conclusions: eBEACOPP provides excellent and durable first-line disease control. Shortening the corticosteroid course does not compromise efficacy, potentially reducing toxicity. However, longer follow-ups and larger studies are needed for confirmation.

Glomerular filtration rate is an independent prognostic factor in patients with B-large cell lymphoma.

Chronic kidney dysfunction is associated with increased mortality in multiple cancer types. Preliminary evidence suggests the same to be true for B-large cell lymphomas (B-LCL). To analyze the relationship of glomerular filtration rate (GFR) and outcome of B-LCL in detail we collected data on outcomes of 285 consecutive patients with newly diagnosed B-LCL treated at our institution with standard rituximab-containing regimens who did not have preexisting kidney disease or urinary tract obstruction at presentation. Median age was 59, range 18 to 87, 145 were male and 140 females. Forty-four had GFR < 60 mL/min, 123 had 60 to 90 mL/min, and 118 > 90 mL/min. Median follow-up of surviving patients was 49 months and estimated 3-year survival 76%. In univariate analysis age (P < .001), GFR (P = .014), stage (P < .001), performance status (P = .044), chemotherapy regimen (P < .01), and international prognostic index (IPI) (P < .001) were statistically significant prognostic factors. In multivariate analysis, age and GFR remained the only independent prognostic factors. Subtracting 1 from the IPI score of patients who had GFR > 90 mL/min and IPI > 1 resulted in a prognostic index that divides patients into 3 prognostic groups (low risk = 0-1, intermediate risk = 2-3 and high risk = 4-5) with an acceptable patient distribution frequency (38%, 39%, and 23%, respectively) and improved statistical significance and separation in comparison to IPI (5-year survival rates of 92%, 74%, and 42%, respectively). GFR is an important independent prognostic factor for B-LCL that should be taken into account in clinical decision making and data analysis and probably be incorporated in prognostic indices.

R-CHOEP14 in younger high-risk patients with large B cell lymphoma: an effective front-line regimen with cardiac toxicity: a real-life, single-center experience.

Currently, there is no consensus regarding optimal front-line treatment for younger high-risk patients with large B cell lymphoma. American recommendations list only R-CHOP as standard, while European also include R-ACVBP and R-CHOEP14. We have been routinely using the latter regimen at our institution since 2011 and performed this retrospective real-life single-center study to analyze outcomes. Between September 2011 and April 2019, 66 newly diagnosed patients aged 18 to 60 years with B-large cell lymphoma and high-risk age-adjusted International Prognostic Index score were scheduled to receive 6 or 8 cycles of bi-weekly chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, etoposide, steroids, and rituximab (R-CHOEP14). After a median follow-up of 4.7 years, the estimated 3-year progression-free survival was 87% (95% CI 80-96%) and 3-year overall survival 90% (95% CI 83-98%). Grade ≥ 3 hematological side effects occurred in 83% and infectious in 41% of patients; one patient died of toxicity. Grade ≥ 2 cardiac toxicity occurred in 21% of patients, more frequently than previously reported. The cumulative 5-year risk of congestive heart failure with all-cause mortality as the competing risk was 17%. R-CHOEP14 is a very effective and manageable regimen for younger high-risk patients with B-large cell lymphoma, but the risk of cardiotoxicity warrants further investigations.

Influence of Blood Count, Cardiovascular Risks, Inherited Thrombophilia, and JAK2 V617F Burden Allele on Type of Thrombosis in Patients With Philadelphia Chromosome Negative Myeloproliferative Neoplasms.

INTRODUCTION: Thrombosis is the most common complication in Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms patients. PATIENTS AND METHODS: In a cohort of 258 Ph- myeloproliferative neoplasm patients, the difference between patients with and without thrombosis was analyzed according to genetic thrombophilia factors, JAK2 V617F status and burden allele, blood count, cardiovascular risk factors and age. Patients were also divided in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) subgroups as well as by the type of thrombosis. RESULTS: Analysis of cardiovascular risk factors regarding arterial thrombosis showed that PV patients with thrombosis had higher incidence of diabetes (P = .030), ET patients more often had hypertension (P = .003) and hyperlipidemia (P = .005), while PMF patients had hyperlipidemia (P = .046) and at least one cardiovascular risk factor (P = .044). Moreover, leukocytes > 18 × 109/L and V617F burden allele > 25.7% were statistically significantly different in PV patients (P = .019 and borderline significant at P = .055, respectively), while in ET patients leukocytes > 9.2 × 109/L (P < .001) and age at diagnosis of > 55 years were statistically significantly different (P = .002). PMF patients with V617F burden allele ≤ 34.8% were more prone to thrombosis (P = .032). When comparing patients with and without venous thrombosis, cutoff value of V617F burden allele > 90.4% was significant for PV patients with thrombosis (P = .036), as was > 56.7% for PMF patients with thrombosis (P = .046). Platelets ≤ 536 × 109/L and age at diagnosis > 54 years showed statistically significant difference for ET patients with thrombosis (P = .015 and P = .041, respectively). CONCLUSION: On the basis of our results, a new scoring system for thrombosis risk in PV could be made, while PMF prognostic model may be expanded for better recognition of potential thrombotic risk factors.

High incidence of aseptic hip necrosis in Hodgkin lymphoma patients treated with escalated BEACOPP receiving methylprednisolone.

BACKGROUND: Escalated BEACOPP (eBEACOPP) is an effective but fairly toxic regimen for the treatment of Hodgkin lymphoma (HL). Avascular necrosis (AVN) of femoral head was previously reported to increase in patients treated with eBEACOPP, but so far, no systematic analysis of its frequency has been published. AIMS: To analyse the frequency and identify possible risk factors for AVN development in patients treated with eBEACOPP. METHODS: We identified 26 patients treated with eBEACOPP for newly diagnosed high-risk advanced-stage HL, 25 of whom were alive at the time of study. All patients were invited to participate in a cross-sectional study; 17 patients responded and were evaluated by magnetic resonance imaging and orthopaedic examination. RESULTS: Six patients (35.3%) were diagnosed with AVN after receiving eBEACOPP treatment. AVN was not correlated with age, gender, number of received eBEACOPP cycles, irradiation therapy or cumulative dose of steroids administered. There were significantly more cases of AVN in patients receiving methylprednisolone than prednisone (P = 0.01). CONCLUSION: The use of methylprednisolone was shown to be a risk factor for the development of AVN in patients treated with eBEACOPP and should not be the corticosteroid of choice in the treatment of patients with HL.

Comparison of Branded and Generic Imatinib Plasma Concentrations in Patients With Chronic Myelogenous Leukemia: Unicentric Study.

INTRODUCTION: For over a decade, imatinib has been the first-line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Doubts on the bioequivalence and bioavailability of emerging generic compounds have been expressed. Adequate imatinib plasma concentration ([IPC] ≥1000 µmol/L) is associated with a better chance of optimal treatment response in patients with CML. In this study, we compared the achieved IPCs between the branded compound and its 2 generic forms. PATIENTS AND METHODS: IPCs were compared in 24 consecutive patients with CML in the first chronic phase who changed from branded to generic imatinib. The median age was 49 years (range, 22-76 years). Fifteen of them were male. Six patients were switched to Neopax, 13 to Imakrebin, and 5 patients received both generics consecutively. All compounds were used in an equivalent dose of 400 mg orally once daily for at least 1 month before plasma concentrations were measured. High-performance liquid chromatography was used to determine imatinib plasma concentration from a specimen collected 21 to 24 hours after the last dose. RESULTS: The median IPC achieved with branded imatinib was 1454 µmol/L (range, 485-2707 µmol/L) with 18 patients (75%) having IPC ≥ 1000 µmol/L. For Neopax and Imakrebin, median IPCs were 1717 µmol/L (range, 1249-3630 µmol/L) and 1458 µmol/L (range, 707-880 µmol/L), respectively, with 11 of 11 (100%) and 16 of 18 (89%) patients having IPC ≥ 1000 µmol/L. No significant difference in measured IPCs between all 3 compounds was found (P > .257). CONCLUSION: When taken at equivalent doses, imatinib generics are bioequivalent and comparable in clinical efficacy and have the potential for substantial savings in the treatment cost for CML.

High-dose ifosfamide and mitoxantrone (HDIM) in patients with relapsed or refractory Hodgkin's lymphoma.

Relapsed/refractory Hodgkin's lymphoma (HL) is treated with salvage chemotherapy and autologous stem cell transplantation (ASCT). Optimal chemotherapy is unknown. We retrospectively analyzed outcomes of 58 patients treated with 2 cycles of high-dose ifosfamide and mitoxantrone (HDIM). HDIM consisted of ifosfamide 5 g/m(2)/day and MESNA 5 g/m(2)/day in continuous 24-h infusion (days 1 and 2), MESNA 2.5 g/m(2) over 12 h (day 3), and mitoxantrone 20 mg/m(2) (day 1) administered every 2 weeks. Stem cells were collected after the first cycle. Responding patients proceeded to ASCT. Toxicity was acceptable. Stem cell mobilization was successful in 96 % of patients. Overall response rate was 74 % (89 % in relapsing and 45 % in refractory patients) with 31 % complete remissions. After a median follow-up of 54 months, 5-year event-free survival was 56 % (69 % for relapsing and 35 % for refractory patients), and 5-year overall survival was 67 % (73 % for relapsing and 55 % for refractory patients). Significant adverse prognostic factors were refractoriness to previous therapy and HDIM failure. No differences in outcomes were noted between patients with early and late relapses or between complete and partial responders. HDIM is a well-tolerated and effective regimen for relapsed and refractory HL with excellent stem cell mobilizing properties. Patients failing HDIM may still benefit from other salvage options.

Nodular Prurigo Associated with Mycosis Fungoides - Case Report.

Mycosis fungoides (MF) is the most common type of cutaneous lymphoma and accounts for approximately 50% of all lymphomas arising primarily in the skin. The three types of MF lesions are patches, plaques, and tumors, according to which the disease is traditionally divided into three clinical stages. The clinical course can be protracted and take years or decades. In the final stage, MF evolves to a systemic form of the disease. Nodular prurigo (NP) is still a condition of unknown etiology characterized by papulonodular eruption and intense pruritus. Multiple diseases, including dermatological, systemic, and psychiatric diseases, have been assumed to cause NP. Pruritic skin lesions have been known to precede clinically evident B and T cell lymphomas for years. In the literature, pruritus and NP have been reported in patients affected by systemic Hodgkin and non-Hodgkin lymphomas. Only two cases of cutaneous lymphoma as underlying disease in patients with PN have been reported in the literature. We report a rare case of a patient with concomitant non-Hodgkin skin lymphoma - MF and NP. Our female patient with a 10-year history of MF stage IIb during the last three years had been presenting for regular check-up with itchy, newly formed, rarely disseminated nodules 5-8 mm in diameter on the forearms and lower legs. Sharply limited erythematosquamous, slightly infiltrated foci (as part of MF as the underlying disease) were visible on the trunk and extremities. Extracutaneous involvement of MF was excluded. We performed a biopsy on a nodule from the lower leg to rule out tumor stage MF; the biopsy confirmed NP. We conclude that prurigo nodules should not be confused with tumor stage MF. NP is a therapeutic challenge for any dermatologist. Any underlying diseases should be treated first.

Immunoglobulin heavy/light chain analysis enhances the detection of residual disease and monitoring of multiple myeloma patients.

AIM: To evaluate the clinical utility of incorporating a novel heavy/light chain immunoassay (HLC) into the existing methods for the assessment of multiple myeloma (MM) patients. METHODS: Convenience sera samples from 90 previously treated IgG and IgA MM patients in different disease stages were analyzed. The study was conducted in Clinical Hospital Center Zagreb between 2011 and 2013. The collected sera were analyzed by standard laboratory techniques (serum protein electrophoresis, quantification of total immunoglobulins, serum immunofixation, serum free light chain [FLC] assay) and HLC assay. RESULTS: HLC ratios outside the normal range were found in 58 of 90 patients, including 28 out of 61 patients with total immunoglobulin measurements within the normal range and 5 out of 23 patients in complete response. Both elevated HLC isotype level and abnormal HLC ratio correlated with the parameters of tumor burden, including percentage of plasma cells in the bone marrow (P<0.001 and P=0.002, respectively) and an abnormal serum FLC ratio (for both P<0.001). In addition, abnormal HLC isotype level correlated with serum beta-2-microglobulin level (P=0.038). In terms of prognosis, abnormal HLC isotype level and abnormal HLC ratio were significantly associated with shorter overall survival (P<0.001 and P=0.002, respectively). Interestingly, suppression of the uninvolved (polyclonal) isotype pair, but not other non-myeloma immunoglobulin isotypes, was also associated with a shorter overall survival (P=0.021). In a multivariate analysis, an abnormal HLC ratio and ß2-microglobulin level >3.5mg/L were independent risk factors for survival. CONCLUSION: The new HLC assay has greater sensitivity in detecting monoclonal protein, correlates with tumor burden markers, and affects patients' outcome.

Radiotherapy of primary cutaneous follicle center lymphoma: case report and review of literature.

Primary cutaneous follicle center lymphoma is an indolent primary cutaneous B-cell lymphoma originating from the follicle center cells, composed of a combination of centrocytes (small and large cleaved cells) and centroblasts (large noncleaved cells) with a follicular, follicular/diffuse, or diffuse growth pattern. Lesions are mostly located on the head, neck and trunk. A case is presented of a 56-year-old male patient with primary cutaneous follicle center lymphoma, with lesions involving the skin of the back, shoulders, presternal area and right forearm. As the patient presented a disseminated cutaneous form of the disease that involved several anatomical regions, complete work-up was followed by superficial fractionated radiotherapy of eight fields in VI expositions, with total irradiation dose of 1400 cGy upon the following fields: right and left pectoral region, left and right shoulders, right suprascapular region, and proximal third of the right forearm. Total irradiation dose applied upon each field for the lesions located on the left and right side of the back was 1500 cGy. This therapy resulted in significant reduction of visible tumor. The patient was regularly followed up on outpatient basis for 12 months of radiotherapy, being free from local recurrence and systemic spread of the disease.

Prognostic significance of survivin and caspase-3 immunohistochemical expression in patients with diffuse large B-cell lymphoma treated with rituximab and CHOP.

Survivin is an inhibitor of apoptosis whose expression may be associated with inferior outcome in patients with diffuse large B-cell lymphoma (DLBCL) treated without rituximab. Caspase-3 is the final caspase of the apoptotic cascade and its pattern of expression may also be related to patients' outcome. In this study we investigated immunohistochemical expression of survivin and caspase-3 (CPP32) in 57 patients with DLBCL treated with rituximab and CHOP (R-CHOP). According to previously published criteria, we separately analyzed correlation of different types of survivin expression with patients' outcome. Nuclear survivin was expressed in only 26% of cases, cytoplasmic survivin was expressed in 81% of cases while application of immunoreactivity scoring system yielded 58% of survivin positive cases. Caspase-3 was expressed in 77% of cases. There were no significant correlations between any type of survivin expression and response to treatment or survival of the patients. The expression of caspase-3 was also not associated with patients' outcome. We conclude that survivin and caspase-3 have no significant prognostic significance in patients with DLBCL treated with R-CHOP.

FNA based diagnosis of head and neck nodal lymphoma.

Fine-needle aspiration (FNA) biopsy has become a well established technique in the diagnosis, staging, and follow-up of patients with head and neck lesions. As in lymphoma diagnostics, FNA serves as a screening method in evaluating potentially affected lymph node for open or core biopsy. According to the World Health Organization classification of lymphoid neoplasms, today it is important to recognize cell morphology and reveal its phenotype, then combine it with different genotypic information and clinical data to provide appropriate therapy. The aim of this study was to assess the efficacy of FNA and immunocytochemistry based lymphoma diagnostic in head and neck region. We conducted a retrospective study during a period of three years where cases with either FNA diagnosis or clinical suspicion of newly recognized or relapsing lymphoma were reviewed. In the study were included patients that were referred to our laboratory from hematology department, in whom head and neck lymphadenopathia was found and lymph node FNA preceded other procedures. Two hundred eighty-five aspirations from 248 patients fulfilled study criteria. Adequate specimens were diagnosed as lymphoma in 100 cases (36%), in 65 male and 35 female patients, 76 in patients with newly discovered disease and 24 in patients with prior lymphoma diagnosis. Overall sensitivity of FNA specimens in the diagnosis of head and neck lymphomas was 90%, specificity 88%, predictive value of a positive result 97%, and predictive value of negative result 61%. Based on our results FNA corroborated with immunophenotyping by immunocytochemistry can be method of choice in primary lymphoma diagnosis as a method complementary to histopathology in lymphoma diagnostics.

Lack of prognostic significance of the germinal-center phenotype in diffuse large B-cell lymphoma patients treated with CHOP-like chemotherapy with and without rituximab.

The influence of the germinal-center B-cell (GCB) and the non-GCB phenotypes of diffuse large B-cell lymphoma (DLBCL) on the outcome of 92 patients treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like chemotherapy, with or without rituximab was determined in this study. The differentiation between the GCB and non-GCB types was arrived at by immunohistochemistry using previously published criteria. Thirty-nine patients had the GCB and 53 had the non-GCB type of DLBCL. Forty-nine patients were treated with rituximab and chemotherapy; 43 were treated with chemotherapy alone. The GCB and non-GCB group did not differ in their international prognostic index factors and score, presence of bulky disease, or frequency of rituximab treatment. Median follow-up of the surviving patients was carried out for 37 months. There was no difference between the GCB and non-GCB groups in both overall response rates (67 vs. 70%, respectively) and estimated rates of 3-year event-free (46 vs. 49%, respectively) and overall (54 vs. 56%, respectively) survival. In addition, no differences of the outcomes were observed between the subgroups treated with or without rituximab. The patients of this study with immunohistochemically determined GCB-type DLBCL did not have an improved prognosis, irrespective of whether they had received rituximab or not.

CD43 expression is an adverse prognostic factor in diffuse large B-Cell lymphoma.

BACKGROUND: CD43 is a transmembrane glycoprotein expressed in different hematopoietic cells, including some subsets of B lymphocytes. About a quarter of diffuse large B-cell lymphomas (DLBCLs) express CD43, but its prognostic significance is unknown. PATIENTS AND METHODS: We analyzed the prognostic effect of immunohistochemically determined CD43 expression in 119 patients with newly diagnosed DLBCL. All were treated with CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone)-like chemotherapy, 57 without and 62 with rituximab. RESULTS: A total of 31 DLBCL cases (26%) expressed CD43. Patients with CD43+ and CD43- lymphomas did not differ regarding sex, International Prognostic Index (IPI) factors and score, rituximab treatment, presence of bulky disease, or germinal center subtype. Median follow-up was 45 months. Patients with CD43+ DLBCL had significantly lower complete response rates (59% vs. 80%; P = .019), 2-year event-free survival (EFS) rates (34% vs. 64%; P = .003), and overall survival (OS) rates (45% vs. 76%; P = .002). The prognostic significance of CD43 expression was retained in multivariate analysis (relative risk [RR] 2.04; P = .013 for EFS; RR 2.17; P = .016 for OS). In subgroup analysis, the effect of CD43 expression was significant in patients treated with rituximab and those with low IPI, whereas it was not reached in patients treated without rituximab. The effect was not observed in patients with high IPI. CONCLUSION: These results indicate that CD43 expression is an important independent adverse prognostic factor in DLBCL.

Treatment of multiple relapsing non-melanoma skin cancers in a patient with severe hemophilia A.

Although non-melanoma skin cancers are the most predominant malignancies in the Caucasian population and hemophilia A is one of the most frequent hereditary bleeding disorders, medical literature data about the management of non-melanoma skin cancers in patients with hemophilia are surprisingly scarce. In this case report we describe the treatment of a patient with multiple recurrent non-melanoma skin cancers and severe hemophilia A. The management of such patients could be very challenging, with possible significant bleeding complications, and requires a multidisciplinary approach.

[Anagrelide for treatment of patients with essential thrombocythaemia]. / Anagrelid u lijecenju bolesnika s esencijalnom trombocitemijom.

Anagrelide is an imidazokinazoline derivate that reduces platelet production by interfering with megakaryocyte proliferation and maturation. As a non-cytostatic drug it selectively affects megakaryocyte lineage and therefore anemia and leukocytopenia are not likely to occur. This makes anagrelide adequate for the treatment of chronic myeloproliferative disorders characterized by marked thrombocytemia. In this study we have evaluated efficacy of anagrelide in 14 pretreated patients with essential thrombocytemia. The response was achieved in 11 patients (78%) and was defined as a platelet count lower than 450 x 10(9)/l or 700 x 10(9)/l without thrombohemorrhagic incidents. The therapy was stopped in 6 patients; three patients did not respond to treatment; one had a serious side effect; pregnancy was the reason for discontinuation of therapy in one patient, and in one patient therapy was changed by his own request. We can conclude that anagrelide is an effective and safe drug for pretreated patients with essential thrombocythemia.

Treatment of cancer-related anemia.

Anemia with consequent tissue hypoxia is common problem in cancer patients. Developed via various patophysiological mechanisms, it has deleterious effect on quality of life and survival of patients with cancer. Recognition of symptoms and timely initiation of treatment improve patients' quality of life, as well as efficacy of oncological treatment. Red blood cells transfusions are well known and efficient way of anemia correction. They are "golden standard" in treatment of cancer-related anemia today, and are unavoidable in almost all patients with hemoglobin concentration below 80 g/L. Newest therapy guidelines in developed countries, supported by recent literature, encourage use of recombinant human erythropoietin (rHu-EPO), although detailed meta-analyses and prospective randomized clinical trials have shown that rHu-EPO decreases the need for transfusions in only 9-45% patients with cancer, only if they have mild anemia, rHu-EPO increases incidence of thromboembolic events, and suspicion arises that it supports tumor cells growth and multiplication. Therefore, it is necessary to define subgroups of patients which are best candidates for rHu-EPO therapy, to accomplish lower intensity of transfusion therapy.

Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids.

Erdheim-Chester disease (ECD) is a rare histiocytosis usually affecting the skeletal system, but visceral organs and central nervous system involvement are common as well. Probability exists that immunomodulatory therapies and disorders can play a role in clinical course of the disease. Because of rarity of the disorder, it is hard to classify it and standardize the treatment options, but, according to published material and our experience, cytotoxic chemotherapy and long-term steroids have therapeutic benefit. Although this approach can probably be accepted as standard of care management, novel therapeutic modalities should be explored, and pathogenesis and disorder classification should be cleared out as well. The case of ECD affecting skeletal system and lungs and concomitant laryngeal tuberculosis successfully treated with chemotherapy and long-term steroid therapy is presented.