Cutaneous Biopsy Research Articles

Secondary Multiple Cutaneous Metastases from Primary Gastric Signet-Ring Cell Adenocarcinoma

A 60-year-old man was diagnosed with gastric cancer by endoscopy in our cancer center. Preoperative CT scan showed thickening of the cardia and enlarged lymph nodes in hepatogastric space. Consequently, he accepted total gastrectomy and Roux-en-Y reconstruction. Immunohistochemical detection showed intense positivity for GST-n and Pgp antibodies and negativity for EGFR, ERCC1, P53, Ki67 and HER-2. Surprisingly, within one month, the patient had multiple asymptomatic cutaneous nodules in the left neck, right subclavian, left armpit, left upper abdomen, lower abdomen, right groin and lumbodorsal region. Abdominal CT scan showed a 22 × 22 mm high-density lesion in the splenorenal space, as well as cutaneous nodules in the left upper abdomen, lower abdomen and right groin. Histopathologic examination of cutaneous biopsy showed a poorly differentiated signet-ring cell carcinoma consistent with a diagnosis of secondary metastasis of primary gastric carcinoma. The patient received “DOF” chemotherapy which do benefit to halt the disease progression. He decided not to continue with chemotherapy and died of multiorgan metastasis 2 months later.

A young girl with H syndrome and coeliac disease

H syndrome is an autosomal recessive genodermatosis with reports dating back to the last decade. This syndrome is caused by mutations in the SCL29A3 gene. The clinical characteristics of this syndrome consist of dermatological manifestations, including hyperpigmented, hypertrichotic, and indurated patches and plaques. It affects various systems by causing heart anomalies, hepatosplenomegaly, hypogonadism, and low height. This is the case of a 19-year-old girl from the northwest of Iran who was born of a cousin marriage. The primary manifestations included low height, underdeveloped secondary sex characteristics, and typical dermatological manifestations. This patient was examined mostly because of digestive and endocrine problems and thus had not been subject to extensive dermatological examinations until the skin biopsies mirrored manifestations similar to histiocytoses (e.g., Rosai-Dorfman disease and granuloma annulare). The patient was eventually diagnosed with H syndrome by a dermatologist from the clinical symptoms. H syndrome is an autosomal recessive genodermatosis that affects different organs and is diagnosed by a set of typical and systemic cutaneous symptoms and biopsies. In this patient, an endoscopic examination of the upper gastrointestinal tract was carried out due to reports of anemia. A biopsy of the atrophic duodenum region revealed the existence of coeliac disease. However, the comorbidity of coeliac disease and H syndrome has not been previously reported.

Granulomatous Skin Diseases in a Tertiary Care Portuguese Hospital: A 10-Year Retrospective Study.

Granulomatous skin diseases comprise an extensive group of pathologies whose diagnosis usually requires a histopathological examination. At this level, various types of granulomas can be distinguished, namely tuberculoid, sarcoid, necrobiotic, suppurative, xanthogranuloma, and foreign-body granulomas. This study aimed to determine the frequency and pattern of different granulomatous skin lesions in the Dermatopathology Department of Hospital de Santa Maria (Lisboa, Portugal). A retrospective study of all skin biopsies with granulomatous lesions received during a period of 10 years (2008-2017) was performed. Clinical and histopathological characteristics of the selected cases were analyzed, and the lesions were categorized according to histological type of granuloma and etiology. Foreign-body granulomas secondary to ruptured cyst, folliculitis, or suture material were excluded. From a total of 48,253 cutaneous biopsies performed in this period, 461 (1%) granulomatous lesions were included in our study. In the analysis according to type of granuloma, necrobiotic granulomas were the most frequent (N = 111; 27.0%), followed by sarcoidal (N = 72; 17.5%), tuberculoid (N = 51; 12.4%), suppurative (N = 45; 10.9%), foreign body (N = 40; 9.7%), and xanthogranulomas (N = 26; 6.3%). The remaining 20% corresponded to granulomas of other types. During these 10 years, the most frequent etiology was granuloma annulare (N = 98; 88.3%), followed by sarcoidosis (N = 47; 65.3%). Histopathology is a fundamental tool in the diagnosis of granulomatous skin diseases, allowing for the categorization of various types of granulomas and often guiding further investigation of these patients. The geographical area has an influence on the types of granulomas observed, as evidenced by comparing this study with others previously published.

Persistent Facial Oedema and Erythema in a Woman, An Uncommon Manifestation of Chronic Cutaneous Lupus Erythematosus.

Manifestations of chronic cutaneous lupus erythematosus are variable. Periorbital and facial swelling occurs in dermatomyositis and systemic lupus, but it has been rarely reported as a manifestation of exclusively cutaneous lupus. A 48-year-old woman presented with a 16-year history of asymptomatic, bilateral swelling and erythema of her face with marked worsening after sun exposure. No systemic symptoms were associated. A complete evaluation did not reveal other findings. Cutaneous biopsy showed features of lupus erythematosus. She was treated with photoprotection, topical tacrolimus, hydroxychloroquine and azathioprine with a partial response. Facial swelling with erythema represents quite an unusual manifestation of chronic cutaneous lupus erythematosus. Dermatomyositis, systemic lupus and Morbihan disease are the main differential diagnoses.LEARNING POINTSPeriorbital and facial swelling with erythema are clinical manifestations of dermatomyositis and systemic lupus erythematosus. However, these manifestations represent quite an unusual presentation of chronic cutaneous lupus erythematosus.The periorbital area is most frequently affected, while extensive facial involvement is much more unusual.A complete evaluation and cutaneous biopsy are essential to make the diagnosis and to rule out other disorders such as dermatomyositis, systemic lupus erythematosus and Morbihan disease.

The Assessment of Polysaccharides, Mucosubstances and Colagen IV in Kindler Syndrome

Kindler syndrome is a rare autosomal recessive genodermatosis characterized by particular fragility of the skin and mucosa, manifesting in the appearance of bullae in minor traumas, photosensitivity, diffuse cutaneous atrophy and progressive poikiloderma. It is caused by mutations in the FERMT1 gene encoding kindlin-1. We present the case of a 12-year-old girl diagnosed with Kindler syndrome showing the classical clinical features affecting the skin, in addition to nail involvement, gingivitis, periodontitis, growth retardation, mental retardation, esophageal and anal stenosis. The histopathological examination of a cutaneous biopsy revealed the presence specific features of Kindler syndrome. Keywords: Kindler syndrome, photosensitivity, esophageal and anal stenosis, skin biopsy

A rare entity of chronic ulcerative stomatitis - A case report

A rare entity of chronic ulcerative stomatitis - A case report - IJOHD- Print ISSN No: - 2395-4914 Online ISSN No:- 2395-499X Article DOI No:- 10.18231/j.ijohd.2019.053, International Journal of Oral Health Dentistry-Int J Oral Health Dent

Could a Cutaneous Lesion Mean Gastric Cancer? Case Report of a Rare Diagnostic Tool and the Management of a Cardiac Complication during Chemotherapy

Cutaneous presentation of gastric cancer is very rare. This case report is about a patient with a metastatic gastric cancer in which the diagnosis was made by a cutaneous biopsy. Following this unusual diagnostic tool, the patient had an intracardiac thrombus, during the chemotherapy regimen, which wasn’t a contraindication for pursuing chemotherapy treatment for over 12 months. This case report is presented to make clinicians aware of a possible atypical sign of presentation of gastrointestinal tract cancer, as well as the importance of clinical suspicion of a well-known problem affecting cancer patients such as venous thromboembolism and its repercussions in the treatment options.

Kaposi’s Disease (KS) in a Senegalese Child Living with HIV

Kaposi’s Disease or Kaposi’s Sarcoma (SK ) is a multifocal malignant proliferation induced by viral growth factors, including interleukin 6 of human herpes virus type 8 (HHV8). We describe four forms of this disease who poses a real public health problem in East and Central Africa. The purpose of our observation was to report a rare condition in a Senegalese HIV-positive child. It was an 11-year-old girl from a region in central Senegal. She was an orphan of both parents, tested and monitored since the age of 5 for HIV infection 1. She was on the 1st line protocol. Due to a lack of support and good observance, she was referred to us at the age of 11 for follow-up in our structure in the suburbs of Dakar. The initial follow-up assessment showed a very low CD4 count and a very high viral load. Before the lack of clinical and immune-virological response, a genotypic resistance test was performed and showed immunological and virological failure. The initial development was marked by the appearance of lesions which were highly suggestive of Kaposi’s disease. She was on 2nd line treatment. The histopathological aspect of cutaneous biopsy was very suggestive of Kaposi’s disease. The subsequent course after ART and bleomycin treatment was clinically marked by regression of skin lesions. Virologically, it was marked by a fall in the viral load. Immunologically there was a gradual recovery of CD4 levels which came back to normal. Our observation demonstrates that absence of effective antiretroviral therapy for HIV increases the risk to develop Kaposi’s sarcoma.

Crops of Papules and Papulonodular Plaques- An Unusual Presentation of Cutaneous Metastasis- A Case Report

Cutaneous Metastasis refers to a growth of neoplastic cells in the skin originating from an internal malignancy. Morphologically the metastasis could take multiple morphologies. We report a case of cutaneous metastasis in a female of age 34years. She initially presented with a 2 years history of progressive appearance of multiple asymptomatic clusters of monomorphic papulonodular lesions widespread on her trunk, lower limbs and genitalia later developed dyspnoea and weight loss. Chest CT showed moderate pleural effusion and multiple lymphadenopathies and right sided lung mass/consolidation. Histopathological evidences of cutaneous biopsy revealed cutaneous Metastasis consistent with the lung primary.

Mummified Cells are a Common Finding in Cutaneous Hodgkin Lymphoma and Can Be Used as a Diagnostic Clue.

Specific cutaneous involvement in Hodgkin lymphoma is rare. In cutaneous lesions, the diagnosis is usually based on the recognition of diagnostic Reed-Sternberg cells and its variants. In nodal Hodgkin lymphoma, so-called mummified cells (cells with condensed cytoplasm and pyknotic eosinophilic or basophilic nuclei) are often seen. They are sometimes conspicuous and easy to recognize, thus serving as a clue to the diagnosis. Our objective was to study cases of cutaneous Hodgkin lymphoma to identify the occurrence of mummified cells. We studied 12 patients (4 women and 8 men; age range 23-80 years). In 6 patients, cutaneous and extracutaneous disease was identified almost simultaneously; in 4 patients, lymph node disease preceded cutaneous involvement; and in the remaining 2 patients, the skin lesions were the presenting sign, whereas lymph node involvement occurred later. Histopathological, immunohistochemical, and molecular-genetic studies, including rearrangements for TCR, IgH genes, and PCR for EBV, were performed. Cutaneous biopsy specimens revealed either a multinodular or diffuse infiltrate, included small lymphocytes, eosinophils, plasma cells, and macrophages, but in all cases, diagnostic Reed-Sternberg cells and its variants were identified. Mummified cells were detected in 9 cases, either as occasional scattered mummified cells often requiring a search (6 cases) or being conspicuous, grouped and therefore easily identified (3 cases). Immunohistochemically, in all 7 cases studied, mummified cells were positive for both CD30 and CD15. It is concluded that mummified cells are encountered in a majority of cases of cutaneous Hodgkin lymphoma.

Intravascular Colonization of Kaposi Sarcoma: Expanding the Spectrum of Specific Infiltrates of B-Cell Chronic Lymphocytic Leukemia

B-cell chronic lymphocytic leukemia (CLL), a low-grade malignancy consisting of CD5(+), CD23(+), and CD43(+) small B lymphocytes, is the most frequent leukemia in the western world. Patients with CLL may exhibit skin changes characterized by histopathologic evidence of infiltration by atypical B lymphocytes, also known as "specific cutaneous infiltrates of CLL"; in addition, CLL is known to be associated with an increased risk of second cancers, including Kaposi sarcoma (KS). The combination of KS and CLL within the same cutaneous biopsy specimen has only rarely been described. We report a peculiar case of KS occurring in a patient with CLL, in which histopathological evaluation of KS lesions revealed prominent accumulation of CLL lymphocytes within neoplastic vascular spaces. We believe that our findings represent a novel example of intravascular colonization of vascular neoplasms by neoplastic lymphoid cells, further expanding the evergrowing spectrum of specific cutaneous infiltrates of CLL.

Dermatologic Manifestations in HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis

Abstract- The human T cell lymphotropic virus type-1 (HTLV-1) is associated with adult T cell leukemia/lymphoma (ATL) and other disorders, including a slowly progressive demyelinating paraparesis, known as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Dermatologic manifestations are common in patients infected with HTLV-1 infection. In this study, we evaluated the dermatologic lesions associated with HAM/TSP patients in Mashhad, Iran. Dermatological findings of 37 patients with HAM/TSP were investigated and compared with those of an HTLV-1 negative control group. A cutaneous biopsy was performed as needed, and the results were statistically analyzed. Results of the present study showed that 34 cases with HAM/TSP (91.9%) and 24 cases in the control group (64.9%) had at least one skin lesion or history of skin lesion before (P=0.010). Xerosis was found in 22 persons (59.5%) in the case group and 4 persons in the control group (10.8%) (P=0.000). Only xerosis was significantly associated with HAM/TSP. Skin manifestations were quite frequent in patients with HAM/TSP. Xerosis was significantly associated with HAM/TSP

Neoplastic cells parasitized by Mycobacterium leprae: report of two cases of melanocytic nevus and one of basal cell carcinoma

BackgroundLeprosy is a major public health concern in many developing countries. Mycobacterium leprae (M. leprae), the causative agent of leprosy, has the ability to parasitize different types of human cells and tissues. In this article, the uncommon parasitism of nevus and neoplastic and epithelial cells by M. leprae are described using histological sections doubly stained by Fite-Faraco (FF) and immunohistochemistry (IHC), respectively.Case presentationThree patients with borderline-lepromatous and lepromatous leprosy underwent excision of melanocytic nevi (cases 1–2) and basal cell carcinoma (case 3). Histological sections confirmed the clinical diagnosis of melanocytic nevus and basal cell carcinoma, but leprosy lesions were evident in adjacent tissues. FF staining and IHC (CD68, Melan A, and 34βE12) demonstrated the presence of bacilli within the nevus cells and also in the epithelial cells of the basal cell carcinoma.ConclusionsM. leprae has the ability to parasitize different types of cells, including neoplastic cells. Pathologists working in settings where leprosy is endemic should be aware that some cutaneous biopsy specimens may also present with leprosy findings.

Investment of both essential fatty and amino acids to immunity varies depending on reproductive stage.

Trade-offs among the key life-history traits of reproduction and immunity have been widely documented. However, the currency in use is not well-understood. We investigated how reproducing female side-blotched lizards, Uta stansburiana, allocate lipids versus proteins when given an immune challenge. We tested whether lizards would invest more in reproduction or immunity depending on reproductive stage. Females were given stable isotopes (15 N-leucine and 13 C-1-palmitic acid), maintained on a regular diet and given either a cutaneous biopsy or a sham biopsy (control). Stable isotopes were monitored and analyzed in feces and uric acid, skin biopsies, eggs, and toe clips. We found that lizards deposited both proteins and lipids into their healing wounds (immune-challenged), skin (control), and eggs (all) and that catabolism of proteins exceeded incorporation into tissue during wound-healing. Specifically, we found that healed biopsies of wounded animals had more leucine and palmitic acid than the nonregrown skin biopsies taken from unwounded control animals. Earlier in reproduction, lizards invested relatively more labeled proteins into healing their wound tissue, but not into unwounded skin of control animals. Thus, reproduction is sometimes favored over self-maintenance, but only in later reproductive stages. Finally, we documented positive relationships among the amount of palmitic acid deposited in the eggs, the amount of food eaten, and the amount of palmitic acid excreted, suggesting higher turnover rates of lipids in lizards investing highly in their eggs.

Genetic study, histochemical analysis and neuroimaging profile in Brazilian patients with cadasil

Analyze the histochemical aspect of granular osmiophilic material in cutaneous biopsy, evaluate morphometrically white matter in cerebral MRI and study of variants of the NOTCH3 gene in patients with suspected CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy). Human gDNA from freshly drawn peripheral blood samples was extracted using a commercial illustra bloodgenomic Prep Mini Spin Kit. Variants in exons 3 and 4 of the NOTCH3gene were screened by Sanger Sequencing method. Brain morphological evaluation by 3-Tesla MRI. For ultrastructural analysis, skin samples were fixed in 2.5% glutaraldehyde, postfixed in 1% osmium tetroxide, dehydrated in acetone and embedded in Epon. Analysis of vessel wall structure was performed by transmission electron microscopy on skin. 20 suspected cases were evaluated. We found fifteen patients to be heterozygous for the pathogenic allele variant c.457C>T (Arg153Cys; rs797045014*T) from the ten probably unrelated kindreds. One patient is heterozygous for the pathogenic allele c.328C>T (Arg110Cys; rs775836288*T), Figure1. All patients with pathogenic allele had MRI lesions; MRI morphometric analyses revealed higher lesion load in frontal and temporal lobes and in deep areas (internal and external capsule, basal ganglia, thalamus), brainstem and cerebellum; in one case we observed spinal cord involvement. We searched for granular Electron-dense Extracellular Material (GOM) located in the internal part of the media, reaching the basal lamina, in four patients (Figure2). For assessment of CADASIL, association between skin biopsy and electron microscopy, study of pathogenic variants in exons 3 and 4 of the NOTCH3gene and MRI morphometric study, increase the sensitivity for a correct diagnosis.

Radiation-induced angiosarcoma of the breast: A review.

Angiosarcoma is a rare, aggressive malignant vascular neoplasm with poor prognosis that has a predilection for skin and superficial soft tissue. It can arise spontaneously or in association with factors like chronic lymphedema or radiation therapy. Radiotherapy used to treat invasive breast tumors is a known risk factor for the development of the so-called radiation-induced angiosarcoma (RIAS), a condition that has been described in the literature with increasing frequency. Radiation-induced angiosarcoma of the breast usually arises on the previously irradiated skin area several years after radiotherapy and presents as painless multifocal erythematous patches or plaques similar to a hematoma. Cutaneous biopsy is essential for the diagnosis. Histologically, RIAS is characterized by irregular anastomosing vessels lined by endothelial cells showing nuclear atypia. Treatment is mostly surgical, and mastectomy with negative margins is considered the standard procedure. However, recurrences are common, and an approach combining surgery, chemo- and radiotherapy may be more effective. The purpose of this study is to review the most recent medical literature on RIAS of the breast, with emphasis on its pathophysiology, clinical and histological features and current treatment options.

PI3K (Phosphatidylinositol 3-Kinase) Activation and Endothelial Cell Proliferation in Patients with Hemorrhagic Hereditary Telangiectasia Type 1.

Hemorrhagic hereditary telangiectasia (HHT) type 2 patients have increased activation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway in telangiectasia. The main objective is to evaluate the activation of the PI3K pathway in cutaneous telangiectasia of HHT1 patients. A cutaneous biopsy of a digital hand telangiectasia was performed in seven HHT1 and eight HHT2 patients and compared with six controls. The study was approved by the Clinical Research Ethics Committee of our center. A histopathological pattern with more dilated and superficial vessels that pushed up the epidermis was identified in HHT patients regardless of the type of mutation and was associated with older age, as opposed to the common telangiectasia pattern. The mean proliferation index (Ki-67) was statistically higher in endothelial cells (EC) from HHT1 than in controls. The percentage of positive EC for pNDRG1, pAKT, and pS6 in HHT1 patients versus controls resulted in higher values, statistically significant for pNDRG1 and pS6. In conclusion, we detected an increase in EC proliferation linked to overactivation of the PI3K pathway in cutaneous telangiectasia biopsies from HHT1 patients. Our results suggest that PI3K inhibitors could be used as novel therapeutic agents for HHT.

Skin lesions in chronic myeloid leukemia patients during dasatinib treatment.

PurposeIn our work we sought to define the prevalence rates of cutaneous events during dasatinib therapy in chronic myeloid leukemia (CML) patients and to investigate the clinical and pathological characteristics of these reactions.Patients and methodsIn our institution, 67 CML patients were treated with dasatinib. it was given as first line treatment in 26 (39%) and subsequent treatment in 41 (61%) CML patients. Flow cytometry analysis of peripheral blood and cutaneous biopsy was done on all CML patients with dermatological lesions appearing during dasatinib treatment.ResultsAmong 67 CML patients, 4 (5.9%) showed skin lesions during dasatinib treatment. The cutaneous manifestations were not generalized but mainly located on the back, abdomen, thorax or leg regions. The patients did not show peripheral lymphocytosis at the time when skin lesions appeared. Overall, histological analysis showed that the skin lesions were characterized by a mild perivascular small CD8+ T lymphocytes infiltrate with minimal epidermotropism.ConclusionThe unusual T cytotoxic cutaneous infiltrate demonstrated in our CML cases could be the expression of a dasatinib-promoted lymphocyte expansion. However, the heterogeneity of the dermatologic manifestations reported in our CML patients could also be related to unknown factors specific to each CML patient. Our work highlights the finding that skin lesions may be associated with dasatinib treatment and that they should not be confused with viral or bacterial infections but rather interpreted as the clinical expression of lymphocytosis promoted by this TKI.

Cellulitis of the face associated with SENLAT caused by Rickettsia slovaca detected by qPCR on scalp eschar swab sample: An unusual case report and review of literature

BackgroundTick-borne rickettsioses are infectious diseases caused by obligate intracellular Gram-negative bacteria belonging to the spotted fever groupof Rickettsia. MethodsWe describe an unusual case of SENLAT (Scalp eschar and neck lymphadenopathy after tick bite), caused byRickettsia slovaca, associated with a cellulitis of the face in a 70-year-old woman, and diagnosed using qPCR on a scalp eschar swab. We review the literature regarding cases of SENLAT-associated-cellulitis and case of SENLAT diagnosed by qPCR on scalp eschar swabs. ResultsWe found only one previous report of SENLAT associated with a cellulitis of the face. It was a nine-year-old French girl diagnosed by seroconversion for Rickettsia sp. Our review of the literature showed that qPCR on eschar swab samples is a less invasive method than performing cutaneous biopsy of the eschar and has good sensitivity and specificity (90% and 100%, respectively). ConclusionsWe report the second case of cellulitis of the face associated with the SENLAT syndrome. Detection of Rickettsia by qPCR on swab sample of the scalp eschar is a simple, noninvasive technique allowing rapid diagnosis and treatment when SENLAT is suspected.

PS1161 EFFICACY AND SAFETY OF IBRUTINIB IN RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS PREVIOUSLY TREATED WITH VENETOCLAX IN THE MURANO STUDY

Background:The BCL2 inhibitor venetoclax (Ven) and the Bruton's tyrosine kinase inhibitor ibrutinib (IBR) have complementary mechanisms of action in chronic lymphocytic leukemia (CLL). As data with targeted agents become available for earlier therapy lines, it is important to understand how to sequence these new regimens best in CLL.Aims:To present a post‐hoc series, obtained after follow‐up from the randomized, phase 3 MURANO study (NCT02005471), of patients (pts) with relapsed/refractory (R/R) CLL who received IBR following fixed‐duration treatment with Ven+rituximab (VenR).Methods:389 pts with R/R CLL were enrolled in MURANO and received 6 cycles of bendamustine (B)+R or 6 cycles of VenR followed by Ven monotherapy once daily for up to 2 years. Primary endpoint was investigator‐assessed progression‐free survival (PFS). This case series reports outcomes for pts treated with VenR in MURANO (IBR‐naïve at study inclusion) who developed progressive disease (PD) and were treated subsequently with IBR.Results:PFS was significantly longer in pts who received fixed‐duration VenR compared with those treated with BR (hazard ratio for overall MURANO population: 0.16 [95% confidence interval: 0.12–0.23]; p < 0.001). As of the May 8, 2018 data cut‐off (median follow‐up: 36 months), 28% of pts (55/194) in the VenR arm had experienced a PFS event (i.e. progression or death, whichever occurred first). Eight pts who had received VenR and experienced a PD event were treated subsequently with IBR (median treatment duration at last follow‐up: 13.5 months [range 3–42]). For these pts, the median number of therapy lines preceding VenR treatment was 1 (range: 1–4). Before VenR treatment, 7 pts had received fludarabine+cyclophosphamide+R (FCR), of whom 3 had achieved complete response (CR), 3 partial response (PR), and 1 had stable disease (SD) on FCR. Two FCR‐treated pts (1 with PR and 1 with CR on VenR) were considered refractory to FCR prior to VenR treatment.Before VenR treatment, 3 pts had a chromosome 17p deletion, 5 had mutated TP53, 1 had chromosome 11q deletion, 4 had unmutated IGVH, 6 had lymph nodes (LN) >10 cm and 2 had LN ≥5–<10 cm. Baseline lymphocyte counts ranged from 0.14 to 388.6 × 109/L, platelets from 59 to 228 × 109/L, and neutrophils from 0.38 to 4.37 × 109/L. Best response to VenR included CR in 3 and PR in 5 pts; 5 pts achieved minimal residual disease negativity at some point during VenR treatment. Chromosomal status and blood cell counts before IBR treatment were unavailable. All 8 pts achieved a response to IBR (7 PR, 1 very good PR). At last follow‐up, 6 pts were still on treatment (of whom 1 was due to stop due to PD after 40 months), 2 had stopped due to PD after approx. 3.5 and 7 months; no pts had died.Four pts had IBR dose modification or interruption due to neutropenia (n = 2), clarithromycin treatment (n = 1), or cutaneous nevus biopsy (n = 1). Multiple skin abscesses were observed in 1 pt. Two pts had arthralgia, 1 case of which had nearly resolved on follow‐up, 1 pt had atrial fibrillation, 1 had pneumonia (without hospital admission), and no instances of major bleeding were reported.Summary/Conclusion:IBR demonstrated an acceptable tolerability profile with no new safety signals as well as good clinical activity in this series of R/R CLL pts who received IBR following VenR treatment in MURANO. IBR treatment, therefore, seems an acceptable option for pts with CLL who relapse following VenR. More data will be gathered from the MURANO study for pts treated with VenR who progress and subsequently receive treatment with IBR.image