Sarcoid-like Lesions Research Articles

Giant Cells of Various Lesions Are Characterised by Different Expression Patterns of HLA-Molecules and Molecules Involved in the Cell Cycle, Bone Metabolism, and Lineage Affiliation: An Immunohistochemical Study with a Review of the Literature.

Giant cells (GCs) are thought to originate from the fusion of monocytic lineage cells and arise amid multiple backgrounds. To compare GCs of different origins, we immunohistochemically characterised the GCs of reactive and neoplastic lesions (n = 47). We studied the expression of 15 molecules including HLA class II molecules those relevant to the cell cycle, bone metabolism and lineage affiliation. HLA-DR was detectable in the GCs of sarcoidosis, sarcoid-like lesions, tuberculosis, and foreign body granuloma. Cyclin D1 was expressed by the GCs of neoplastic lesions as well as the GCs of bony callus, fibroid epulis, and brown tumours. While cyclin E was detected in the GCs of all lesions, p16 and p21 showed a heterogeneous expression pattern. RANK was expressed by the GCs of all lesions except sarcoid-like lesions and xanthogranuloma. All GCs were RANK-L-negative, and the GCs of all lesions were osteoprotegerin-positive. Osteonectin was limited to the GCs of chondroblastoma. Osteopontin and TRAP were detected in the GCs of all lesions except xanthogranuloma. RUNX2 was heterogeneously expressed in the reactive and neoplastic cohort. The GCs of all lesions except foreign body granuloma expressed CD68, and all GCs were CD163- and langerin-negative. This profiling points to a functional diversity of GCs despite their similar morphology.

Granulomatous and Sarcoid-like Immune-Related Adverse Events following CTLA4 and PD1 Blockade Adjuvant Therapy of Melanoma: A Combined Analysis of ECOG-ACRIN E1609 and SWOG S1404 Phase III Trials and a Literature Review.

Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSLs) affecting different organs. This study sought to evaluate GSL incidence in patients with high-risk melanoma treated with cytotoxic T-lymphocyte antigen 4 (CTLA4) or programmed cell death 1 (PD1) blockade adjuvant therapy in two clinical trials: ECOG-ACRIN E1609 and SWOG S1404. Descriptions and GSL severity ratings were recorded. Data were collected from ECOG-ACRIN E1609 and SWOG S1404. Descriptive statistics along with GSL severity grades were reported. Additionally, a literature review for such cases was summarized. A total of 11 GSL cases were reported among 2878 patients treated with either ICI or with High-Dose Interferon Alfa-2b (HDI) in ECOG-ACRIN E1609 and SWOG S1404 trials. Cases were numerically more commonly reported with ipi10, followed by pembrolizumab, ipi3, and HDI, respectively. Most of the cases were grade III. Further, organs involved included lung, mediastinal lymph nodes, skin and subcutaneous tissue, and eye. Furthermore, a summary of 62 reports in the literature was described. GSLs following anti-CTLA4 and anti-PD1 antibody therapy in patients with melanoma were reported unusually. Reported cases ranged in grade from I to III and appeared manageable. Careful attention to these events and their reporting will be essential to better guide practice and management guidelines.

Sarcoid-like lesions obfuscating the diagnosis of disseminated Mycobacterium genavense infection in a patient with IL-12Rβ1-associated immunodeficiency

BackgroundSarcoidosis is a systemic inflammatory disease that is characterized by non-caseating epithelioid-cell granulomas upon histology. However, similar histological findings may also be seen with certain infections. Thus, differentiation from infection is pivotal to ensure appropriate treatment. Here, we present a case of a disseminated infection with Mycobacterium genavense owing to an interleukin 12 receptor subunit beta 1 (IL-12Rβ1) associated immunodeficiency in a previously healthy female who was initially misdiagnosed with sarcoidosis. M. genavense is a nontuberculous mycobacterium which can cause lymphadenopathy, gastrointestinal and bone marrow infiltration in immunocompromised patients. With this case report we aim to highlight that an infection with M. genavense on the ground of a genetic defect of mycobacterial immune control may represent a rare differential diagnosis of sarcoidosis.Case presentationA 31-year-old female was referred to our hospital with progressive lymphadenopathy, hepatosplenomegaly, pancytopenia and systemic inflammation. She had previously been evaluated for generalized lymphadenopathy in another hospital. At that time, lymph node biopsies had revealed sarcoid-like lesions and a systemic corticosteroid treatment was initiated based on a putative diagnosis of sarcoidosis. When her condition worsened, she was transferred to our university clinic, where the diagnosis of disseminated M. genavense infection owing to an inborn interferonopathy was made. Her family history revealed that her brother had also suffered from IL-12Rβ1 deficiency and had died from a systemic infection with M. genavense at the age of 21. The patient received antimycobacterial treatment combined with subcutaneous type I interferon, which eventually led to a gradual improvement over the next months.ConclusionsDifferentiating between sarcoidosis and sarcoid-like lesions secondary to infections may be challenging, especially when pathogens are difficult to detect or not expected in an apparently immunocompetent patient. Patients with IL-12Rβ1-associated immunodeficiency may be asymptomatic until adulthood, and disseminated M. genavense infection on the grounds of an IL-12Rβ1-associated immunodeficiency may represent a rare differential diagnosis of sarcoidosis.

The Development of Novel Primer Sets to Specifically Amplify Each of the Five Different Deltapapillomaviruses That Cause Neoplasia after Cross-Species Infection.

Bovine papillomavirus (BPV) types 1 and 2 are recognized as the main cause of equine sarcoids. However, some studies report that up to a quarter of these tumors do not contain detectible BPV1 or BPV2 DNA. The absence of detectible BPV1 or BPV2 in these sarcoids suggests the possible involvement of other papillomavirus types. Currently, five deltapapillomaviruses are recognized to cause mesenchymal neoplasia after cross-species infection. In addition to BPV1 and BPV2, BPV13 has been associated with equine sarcoids in Brazil, BPV14 has been associated with feline sarcoids, and Ovis aries papillomavirus 2 caused a sarcoid-like lesion in a pig. To investigate the cause of equine sarcoids, PCR primers were developed to specifically amplify each of the five different deltapapillomaviruses that have been associated with mesenchymal neoplasia. The specificity of these primers was confirmed using samples of formalin-fixed tissue known to contain each PV type. These primers allow rapid and sensitive detection of deltapapillomavirus DNA in equine sarcoids. As studies have revealed marked regional variability in the cause of equine sarcoids, these primers will be useful to determine the predominant PV type causing sarcoids in a region. Additionally, there is a single report describing mixed infections by BPV1 and BPV2 in equine sarcoids. The specific primer sets are expected to enable more sensitive detection of mixed infections in equine sarcoids. Determining the cause of equine sarcoids is important as vaccines are developed to prevent these common malignant neoplasms.

1069P Granulomatous and sarcoid-like immune adverse events following CTLA4 and PD1 blockade adjuvant therapy of high-risk melanoma: A combined analysis of ECOG-ACRIN E1609 and SWOG S1404 phase III trials

Treatment with immune checkpoint inhibitors (ICIs) has been linked to granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs. Accurate diagnosis and reporting of such rare events are essential to clinical practice and patient care.

Granulomatous and sarcoid-like immune related adverse events (irAEs) in melanoma patients following CTLA4 blockade adjuvant therapy: An analysis of 1670 high-risk patients.

9582 Background: Granulomatous and sarcoid-like lesions (GSL) affecting the skin, lungs, thoracic lymph nodes, eyes and other organs following treatment with immune checkpoint inhibitors (ICIs) have been described in sporadic reports in the literature but the true incidence is unknown. Methods: We sought to estimate the incidence of GSL in the context of prospectively conducted ECOG-ACRIN E1609 phase III adjuvant trial in high-risk resected melanoma (N=1670 patients) testing ipilimumab 3 mg/kg (ipi3) and 10 mg/kg (ipi10) versus high-dose interferon-α (HDI). Descriptive statistics were used to calculate the incidence. Results: Among 1670 total patients treated with ICIs or with HDI in E1609, 1034 were treated with ipilimumab and 636 with HDI. Six GSL cases were reported among 1670 total patients treated with ipilimumab or with HDI as summarized in the table along with the corresponding CTCAE grades. More cases were observed with ipi10, followed by ipi3 and HDI, respectively. Organs involved included skin and subcutaneous tissue (granuloma annulare, granulomatous dermatitis), eye (ocular sarcoidosis), lymph nodes (noncaseating granulomatous lymphadenitis), lung and mediastinal lymph nodes (sarcoidosis, granulomatous inflammation). Conclusions: The incidence of granulomatous and sarcoid-like lesions (GSL) with adjuvant ipilimumab therapy in high-risk melanoma is rare. Reported cases ranged in grade from 1-3 and appeared manageable. Since most cases are asymptomatic, it is possible that GSLs are under-recognized and therefore, under-reported. A larger analysis including patients treated with anti-PD1 antibodies is currently underway. Clinical trial information: NCT01274338. [Table: see text]

1301P - Deep learning radiomics distinguishes intrapulmonary disease from metastases in immunotherapy-treated melanoma patients

BackgroundMelanoma patients have shown sarcoid-like lesions as an immune-related adverse event to anti-PD-1 immunotherapy. Proper discrimination is essential for accurate treatment decision. Aim of the study is to distinguish granulomatous disease (GD) from pulmonary metastases (MET) and enlarged intrapulmonary lymph nodes (LN) in melanoma patients treated with immune checkpoint blockade by using deep learning. MethodsRetrospective (2012-2018) analysis of 165 melanoma patients treated with anti-PD-1 immunotherapy. All patients underwent standardized imaging-based tumor response assessment with contrast enhanced computed tomography (CT) (follow up interval 8-10 weeks) during treatment. Only patients with intrapulmonary lesions were included (n=132, f=72, median age 63 (IQR 55-74ys). All lesions were clustered in 4 different classes: (1) MET, (2) LN, (3) GD, and (4) small (2-5mm) indeterminate calcified granulomas (GC). GD was histologically proven (guided biopsy or operative excision). All LNs and GCs were identified in CT examinations (1-6 years) prior to diagnosis. For all lesions, a labeled region of interest was extracted by an experienced radiologist (11 years). Automatic classification of intrapulmonary lesions was performed by deep learning (VGG-like model). ResultsIn total, 4409 lesions were labeled (2746 METs (62.3 %), 1143 LNs (25.9%), 328 GC (7.4%), 192 GD (4.4%)). The model predicted instances of these classes for GD, GC or LN with a significant area under the receiver operating curve (ROC) of 0.66, 0.70 and 0.68, respectively (p-value <0.001). The performance of the algorithm was independent of imaging protocol (e.g. contrast enhancement, slice thickness, and reconstructed imaging kernel (soft versus sharp)) with AUC 0.65 for all. ConclusionsDeep learning can help to discriminate between intrapulmonary granulomatous disease, indeterminate calcified granulomas and intrapulmonary lymph nodes in anti-PD-1 treated melanoma patients. Further model development is needed to overcome the imbalanced “real clinical scenario” data to classify granulomatous disease in melanoma patients treated with anti-PD-1 immune checkpoint inhibitor blockade for implementation in the clinical workflow. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Sarcoid-Like Lesions Mimicking Pulmonary Metastasis: A Case Series and Review of the Literature

Background: The association of sarcoid-like lesions and malignancy is well described. Nonetheless, pulmonary lesions in malignant disease are typically presumed metastatic, and do not routinely receive histological validation. Here, we report on pulmonary sarcoid-like lesions identified in patients with a primary malignancy where pulmonary metastatic disease was suspected. Methods: Patients who underwent thoracic surgical procedures for confirmation or treatment of suspected pulmonary metastasis were retrospectively analysed. Results: In 8/186 patients (4.3%), histology revealed sarcoid-like lesions. In these cases, there were no clinical symptoms suggestive of sarcoidosis. All underlying primary malignancies in the sarcoid-like patients were treated with curative intent. The median age of patients with sarcoid-like lesions was 46.3 years (range 26–61). The median interval between primary diagnosis of malignancy and diagnosis of pulmonary lesions was 188 days (range 0–794), with thoracic surgical intervention performed at a median of 250 days (range 183–675). FDG-avidity was demonstrated in the sarcoid-like lesions in 2 out of 3 patients who underwent PET-CT. Conclusion: Sarcoid-like lesions may be challenging to identify and can mimic pulmonary metastases. Therefore, considering sarcoidosis as a differential diagnosis whenever first pulmonary metastasis is suspected is warranted. Carefully considered, histological validation of initial suspected pulmonary metastasis may avoid subsequent over- or undertreatment.

Noncaseating granulomatous diseases in germ cell cancer patients–A single-center experience

ObjectivesIn patients with testicular Germ Cell Tumors (GCT) noncaseating granulomatous diseases such as Sarcoid Like Lesions (SLL) or Sarcoidosis can mimic metastasis due to hilar or mediastinal lymphadenopathy. Due to the clinical and prognostic impact, exclusion of malignant diseases is mandatory. Material and methodsRetrospectively, data from 636 GCT patients, who were seen in the course of tumor surveillance/follow-up were collected. Focus was put on the detection of tumor relapse vs. noncaseating granulomatous reactions. For the differential diagnosis of thoracic lymphadenopathy or pulmonary infiltrates either bronchoscopy (e.g., endobronchial ultrasound-guided transbronchial needle aspiration, endobronchial ultrasound-guided transbronchial needle aspiration) or thoracic surgery was performed. Both GCT patients with either tumor relapse or coexisting SLL were compared to GCT patients without SLL and tumor relapse. ResultsTwenty-nine patients suffered from suspected tumor relapse. Whereas thoracic relapses were suspected in 15 patients on chest computed tomography, thoracic relapse was confirmed in 5 cases by open surgery. In 2 cases open surgery yielded reactive lymphadenitis, and in 8 cases SLL was diagnosed either via EBUS-TBNA (n = 7) or thoracoscopic wedge resection plus lymphadenectomy (n = 1). With focus on overall survival, no relevant difference was found between all tested subgroups (P = 0.265; logrank test). ConclusionsIn GCT patients, the coexistence of noncaseating granulomatous disease is common. Minimal invasive bronchoscopic techniques can serve for the cytopathologic exclusion of malignant thoracic manifestations. In our monocenter patient group the coexistence of SLL did not have any prognostic impact on overall survival.

English

Crohn’s granuloma is a sarcoid-like lesion, with collections of monocyte/macrophages cells (epitheloid histiocytes) and other inflammatory cells, including lymphocytes and eosinophils with occasional giant cells. They are seen rarely in extraintestinal sites. Crohn’s granuloma is highly characteristic of Crohn’s disease. It responds to treatment of Crohn’s disease. A case report of 31 year old male patient with IBD colitis having Crohn’s granuloma on left elbow. On treatment with prednisolone frequency of intestinal symptoms decreased and the ulcerative lesion also healed. Then azathioprine was given for definitive management.

Sarcoid-like lesion is a frequent benign cause of lymphadenopathy in neoplastic patients: Table 1–

To the Editor: Sarcoidosis is a systemic granulomatous disease of unknown origin, characterised by the widespread development of noncaseating epithelioid cell granulomas in more than one organ system. Clinical and radiographic aspects of sarcoidosis and malignancy might mimic one another, making the distinction between the two difficult in some cases. Cancer and sarcoidosis have been associated in some case series but this association remains controversial; several studies from the literature suggest that this association is not fortuitous [1, 2]. Sarcoidosis may precede, follow or occur concurrently with cancer, both haematological malignancies and solid tumours [2]. We wanted to evaluate the incidence of morphological features of sarcoidosis in patients followed up for previous cancer who develop hilar/mediastinal lymphadenopathies with no pulmonary lesions. We performed a retrospective chart review of all patients who were referred to our pulmonology department (Morgagni Hospital, Forli, Italy) in the period between January 2007 and December 2011 with a new onset of hilar/mediastinal lymphadenopathies (with no pulmonary lesions) during follow-up for previous malignancies. Patients underwent endobronchial ultrasound (EBUS) or transoesophageal ultrasound (EUS) trans-bronchial needle aspiration (TBNA) under deep sedation ( i.v. propofol). Lymphadenopathies were diagnosed 49±69 months after the diagnosis of previous malignancy …

SKIN SARCOID-LIKE LESIONS IN CVID WITH POOR OUTCOME

Event Abstract Back to Event SKIN SARCOID-LIKE LESIONS IN CVID WITH POOR OUTCOME Roberto Paganelli1, 2*, Maria C. Turi1, Marika D'Urbano2, Alessia Paganelli1, 2 and Eleonora Celletti1 1 Università G. d'Annunzio of Chieti-Pescara, Medicine and Sciences of aging, Italy 2 Center for Sciences of Aging, Biogerontology and Cytokines, Italy Common variable immunodeficiency (CVID) is a heterogenous immunodeficiency disorder characterized by different clinical presentations. In about 10% of cases they present with granulomatous lesions occurring in spleen, lymphnodes, liver, lungs, skin or conjunctiva. Most patients belong to group-I CVID classification, either with B cells<1% or absent CD21low. The histopathology is similar to sarcoidosis, but its association with CVID occurs in a limited percentage of cases. We describe a CVID case, female aged 56yrs observed in November, 2009, but with clinical history dating from before 1988, with recurrent sinopulmonary infections, chronic diarrhea, low IgG (403 mg/dl) with absent IgA and IgM, treated since 2004 with IVIgs (20g every 2 months); she was diagnosed with cutaneous sarcoidosis in 2006 after a biopsy of a lesion on the left leg. Cutaneous granulomatous lesions appeared soon after in the periocular and perioral regions of the face and in both legs. Calcium levels, ACE, G6PDH were normal, Mantoux test neg, no visceral granulomas were detected by HRTC and US. We started sc Igs which allowed reconstitution of protective levels (to 686 mg/dL serum IgG), and treatments (HCQ, steroids and dapsone) unsuccessful for cutaneous and sinopulmonary new lesions suggesting sarcoidosis. An ocular CMV infection developed, leading to severely impaired sight, lip basal carcinoma and granulomatous lesions of the tongue. Leukopenia was constantly present, with 23% lymphocytes, 88% CD3+, 34% CD4+, 1,3% total and no memory switched B cells. Malignant lymphoma developed late in 2012. Management of this CVID subgroup is difficult and controversial. Keywords: CVID, Sarcoidosis, Skin Diseases, Granuloma, IVIg, Lymphoma, Non-Hodgkin, memory B cells Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Paganelli R, Turi MC, D'Urbano M, Paganelli A and Celletti E (2013). SKIN SARCOID-LIKE LESIONS IN CVID WITH POOR OUTCOME. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01065 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Roberto Paganelli, Università G. d'Annunzio of Chieti-Pescara, Medicine and Sciences of aging, Chieti scalo, Chieti, 66013, Italy, roberto.paganelli2@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Roberto Paganelli Maria C Turi Marika D'Urbano Alessia Paganelli Eleonora Celletti Google Roberto Paganelli Maria C Turi Marika D'Urbano Alessia Paganelli Eleonora Celletti Google Scholar Roberto Paganelli Maria C Turi Marika D'Urbano Alessia Paganelli Eleonora Celletti PubMed Roberto Paganelli Maria C Turi Marika D'Urbano Alessia Paganelli Eleonora Celletti Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Prognostic Significance of a New Grading System of Lymph Node Morphology After Neoadjuvant Radiochemotherapy for Esophageal Cancer

Along with primary tumor response, lymph node (LN) status after radiochemotherapy is one of the most important prognostic factors for advanced esophageal carcinoma. We investigated the influence of neoadjuvant radiochemotherapy on histomorphologic parameters of LNs. One hundred ninety-two patients with esophageal carcinoma underwent surgery after preoperative radiochemotherapy. Response of primary tumor was graded as "minor" or "major." Two matched subgroups were chosen: 20 patients with minor response and 20 patients with major response. Histomorphologic criteria of LNs underwent univariate and multivariate analyses and correlated with tumor response and prognosis statistics. The LNs from 40 patients (N = 1276) were examined (median number of LNs per patient, 31). Of patients with minor response, 65% showed LN metastasis; of those with major response, 20% did so (p = 0.011). Major responders had significantly lower rates of capsular and central fibrosis and vascular transformation and had more sarcoidlike lesions. Logistic regression analysis did not distinguish these parameters between major and minor responders. The 5-year survival rate was 55% for major responders and 10% for minor responders (p = 0.025), 47% for patients with LN metastasis (LNM) and 18% for patients with LNM (p = 0.041). An optimal prognostic factor, LN morphologic grading, was defined as follows: low risk, no LNM and less than 3 LNs with central fibrosis; medium risk, no LNM and central fibrosis in 3 or more LNs or LNM with an LN ratio of less than 0.05; high risk, all other cases. The 5-year survival rate was 56%, 25%, and 0% for patients considered to have low, medium, and high risk, respectively, according to LN morphologic grading (p < 0.003). With the inclusion of this classification in the Cox regression analysis, no other factors showed prognostic relevance. Grading of LN morphology after neoadjuvant radiochemotherapy is the most important prognostic factor for patients with esophageal cancer.

Pathology and immunohistochemistry of papillomavirus-associated cutaneous lesions in Cape mountain zebra, giraffe, sable antelope and African buffalo in South Africa

Skin lesions associated with papillomaviruses have been reported in many animal species and man. Bovine papillomavirus (BVP) affects mainly the epidermis, but also the dermis in several species including bovine, the best-known example being equine sarcoid, which is associated with BVP types 1 and 2. This publication describes and illustrates the macroscopic and histological appearance of BPV-associated papillomatous, fibropapillomatous or sarcoid-like lesions in Cape mountain zebra (Equus zebra zebra) from the Gariep Dam Nature Reserve, 2 giraffes (Giraffa camelopardalis) from the Kruger National Park, and a sable antelope (Hippotragus niger) from the Kimberley area of South Africa. An African buffalo (Syncerus caffer) cow from Kruger National Park also had papillomatous lesions but molecular characterisation of lesional virus was not done. Immunohistochemical staining using polyclonal rabbit antiserum to chemically disrupted BPV-1, which cross-reacts with the L1 capsid of most known papillomaviruses, was positive in cells of the stratum granulosum of lesions in Giraffe 1, the sable and the buffalo and negative in those of the zebra and Giraffe 2. Fibropapillomatous and sarcoid-like lesions from an adult bovine were used as positive control for the immunohistochemistry and are described and the immunohistochemistry illustrated for comparison. Macroscopically, both adult female giraffe had severely thickened multifocal to coalescing nodular and occasionally ulcerated lesions of the head, neck and trunk with local poorly-circumscribed invasion into the subcutis. Necropsy performed on the 2nd giraffe revealed neither internal metastases nor serious underlying disease. Giraffe 1 had scattered, and Giraffe 2 numerous, large, anaplastic, at times indistinctly multinucleated dermal fibroblasts with bizarre nuclei within the sarcoid-like lesions, which were BPV-1 positive in Giraffe 1 and BPV-1 and -2 positive in Giraffe 2 by RT-PCR. The sable antelope presented with a solitary large lesion just proximal to the right hind hoof, which recurred after excision, and was BPV-1 positive by RT-PCR. Other wart-like growths were present elsewhere on the body. The Cape mountain zebra either succumbed from their massive lesions or were euthanased or removed from the herd because of them. The lesions wereBPV-1 and/or -2 positive byRT-PCR. The buffalo lesions were wart-like papillomatous projections in the inguinal and udder region. Stratum granulosum cells that stained immunohistochemically positive in the various species appeared koilocyte-like, as described in human papillomaviral lesions.

Pathology and immunohistochemistry of papillomavirus-associated cutaneous lesions in Cape mountain zebra, giraffe, sable antelope and African buffalo in South Africa

Skin lesions associated with papillomaviruses have been reported in many animal species and man. Bovine papillomavirus (BVP) affects mainly the epidermis, but also the dermis in several species including bovine, the best-known example being equine sarcoid, which is associated with BVP types 1 and 2. This publication describes and illustrates the macroscopic and histological appearance of BPV-associated papillomatous, fibropapillomatous or sarcoid-like lesions in Cape mountain zebra (Equus zebra zebra) from the Gariep Dam Nature Reserve, 2 giraffes (Giraffa camelopardalis) from the Kruger National Park, and a sable antelope (Hippotragus niger) from the Kimberley area of South Africa. An African buffalo (Syncerus caffer) cow from Kruger National Park also had papillomatous lesions but molecular characterisation of lesional virus was not done. Immunohistochemical staining using polyclonal rabbit antiserum to chemically disrupted BPV-1, which cross-reacts with the L1 capsid of most known papillomaviruses, was positive in cells of the stratum granulosum of lesions in Giraffe 1, the sable and the buffalo and negative in those of the zebra and Giraffe 2. Fibropapillomatous and sarcoid-like lesions from an adult bovine were used as positive control for the immunohistochemistry and are described and the immunohistochemistry illustrated for comparison. Macroscopically, both adult female giraffe had severely thickened multifocal to coalescing nodular and occasionally ulcerated lesions of the head, neck and trunk with local poorly-circumscribed invasion into the subcutis. Necropsy performed on the 2nd giraffe revealed neither internal metastases nor serious underlying disease. Giraffe 1 had scattered, and Giraffe 2 numerous, large, anaplastic, at times indistinctly multinucleated dermal fibroblasts with bizarre nuclei within the sarcoid-like lesions, which were BPV-1 positive in Giraffe 1 and BPV-1 and -2 positive in Giraffe 2 by RT-PCR. The sable antelope presented with a solitary large lesion just proximal to the right hind hoof, which recurred after excision, and was BPV-1 positive by RT-PCR. Other wart-like growths were present elsewhere on the body. The Cape mountain zebra either succumbed from their massive lesions or were euthanased or removed from the herd because of them. The lesions were BPV-1 and/or -2 positive by RT-PCR. The buffalo lesions were wart-like papillomatous projections in the inguinal and udder region. Stratum granulosum cells that stained immunohistochemically positive in the various species appeared koilocyte-like, as described in human papillomaviral lesions.

Early 2′-Deoxy-2′-[18F]Fluoro-d-Glucose PET Metabolic Response after Corticosteroid Therapy to Differentiate Cancer from Sarcoidosis and Sarcoid-like Lesions

We aimed at investigating whether early metabolic response to corticosteroid therapy may be used as a diagnostic tool to discriminate between cancer and sarcoidosis, a well-known cause of false-positive 2-deoxy-2-[F-18]fluoro-D: -glucose-positron emission tomography (FDG-PET) findings in oncology. Two cancer patients with biopsy-proven sarcoidosis or sarcoid-like reaction had multiple thoracic FDG foci. After infectious disease had been excluded, patients received oral corticosteroids for 16 and 14 days, respectively, and underwent posttherapeutic FDG-PET examination. Posttreatment PET revealed a complete metabolic response in both patients, and clinical and imaging follow-up showed no sign of cancer progression. Early metabolic response to systemic corticosteroid treatment may be used as a tool in the establishment of final diagnosis when sarcoidosis is suspected in a cancer patient and could be capable of differentiating cancer from sarcoidosis in the case of coexisting diseases.

Solitary plasmacytoma of the lung with coexisting sarcoid-like lesions

Solitary plasmacytoma of the lung with coexisting sarcoid-like lesions

Sarcoid-like lesions associated with the immune restoration inflammatory syndrome in AIDS: absence of polymerase chain reaction detection of Mycobacterium tuberculosis in granulomas isolated by laser capture microdissection

Highly active antiretroviral therapy (HAART)-treated human immunodeficiency virus (HIV)-positive patients can develop granulomatous lesions within the first few weeks of initiating therapy. This immune syndrome, called immune restoration inflammatory syndrome (IRIS), can induce sarcoid-like lesions in tissues. The pathogenesis of these granulomas is currently unknown because no pathogen has been identified to date in the lesions using morphological and/or microbiological approaches. However, the role of certain microbes, such as Mycobacterium tuberculosis, is still debated. The aim of this study was to look for the presence of M. tuberculosis in sarcoid-like lesions occurring in 14 AIDS patients treated with HAART. We used the PCR DNA amplification method in granulomas microdissected from sections stained by hematoxylin-eosin from formalin-fixed, paraffin-embedded specimens. Results were compared to those obtained from microdissected tuberculosis (TB) granulomas (15 patients) and from microdissected sarcoidosis granulomas (12 patients). M. tuberculosis DNA was undetectable from the microdissected sarcoid-like granulomas, whereas DNA from M. tuberculosis was isolated in all the microdissected TB granulomas and was absent in the microdissected sarcoidosis granulomas. Taken together, these data showed that M. tuberculosis DNA is not associated with the presence of sarcoid-like lesions occurring in HIV-positive patients treated with HAART.

EUS-guided fine-needle aspiration of suspected hilar cholangiocarcinoma in potentially operable patients with negative brush cytology.

Despite improvements of diagnostic modalities differentiation between benign and malignant hilar strictures remains a challenge. Hilar neoplasia requires preoperative tissue diagnosis to avoid risk of inappropriate extensive surgery. This is commonly attempted using various techniques at ERCP, which have variable sensitivity and accuracy. We used endosonography-guided fine-needle aspiration (EUS-FNA) for the preoperative diagnosis of hilar cholangiocarcinoma (HC). Prospective evaluation of 44 patients (31 male, mean age: 59 yr) with strictures at the liver hilum were diagnosed by CT and/or ERCP. All were suspicious of HC but had inconclusive tissue diagnosis. They underwent EUS-FNA with linear echo endoscope and 22 gauge needles. Adequate material was obtained in 43 of 44 patients. Cytology revealed HC in 26 and other malignancies in 5 patients; 12 had benign results: sclerosing cholangitis (n = 4), primary sclerosing cholangitis (n = 4), inflammation (n = 3), sarcoid-like lesion (n = 1). There were no significant differences in age, lesion size, or echo features among patients with adenocarcinomas, other malignancies, or benign lesions. Thirty-two patients underwent surgery, 2 had autopsy, 10 were followed up clinically. Four of the benign results were false negatives. No complications occurred. Accuracy, sensitivity, and specificity were 91%, 89%, and 100%, respectively. EUS and EUS-FNA changed preplanned surgical approach in 27 of 44 patients. These results suggest that EUS-FNA is of value as a new, less-invasive approach for tissue diagnosis of hilar strictures of unknown cause. It was technically feasible without significant risks, when other diagnostic tests were inconclusive and was able to change preplanned management in about half of the patients.

Cutaneous sarcoidlike lesions in B-cell chronic lymphocytic leukemia

The development of systemic sarcoidosis in patients with malignancies is a well-known phenomenon. However, cutaneous sarcoidlike lesions are a rare finding. We report 2 patients with B-cell chronic lymphocytic leukemia and hypogammaglobulinemia who presented isolated cutaneous sarcoidlike lesions 9 years after the diagnosis of the hematologic malignancy in one case and after the second course of chemotherapy regimen in the other case. The role of cytokines released from malignant cells and of the hypogammaglobulinemia facilitating an unidentified infectious agent is questionable.