Histopathological Presentation Research Articles

An ANN model for the differential diagnosis of tuberculosis and sarcoidosis.

Sarcoidosis is often misdiagnosed as tuberculosis and consequently mistreated owing to inherent limitations in histopathological and radiological presentations. It is known that the differential diagnosis of Tuberculosis and Sarcoidosis is often non-trivial and requires expertise and experience from clinicians. Therefore, it is of interest to describe a multilayer neural network model to differentiate pulmonary tuberculosis from Sarcoidosis using signal intensity data from blood transcriptional microarray. Genes that are significantly upregulated in Pulmonary Tuberculosis and Sarcoidosis in comparison with healthy controls were used in the model. The model classified Pulmonary Tuberculosis and Sarcoidosis with 95.8% accuracy. The model also helps to identify gene markers that are differentially upregulated in the two clinical conditions.

Advanced pulmonary sarcoidosis.

Mortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies that help to better phenotype these patients, discuss new treatment options, and suggest areas where additional research is needed. Diagnosis and management of advanced pulmonary sarcoidosis has changed as new technologies and treatment options have emerged. Clinical phenotypes of advanced disease have evolved to show overlap in presentation with other interstitial lung diseases. Assessment involves more advanced imaging modalities. New promising treatment options are being studied. Pulmonary rehabilitation and lung transplantation are being utilized to improve health-related quality of life and survival. Patients with advanced pulmonary fibrosis can have variable clinical, radiographic, histopathologic presentation. Given the poor health-related quality of life and high rates of mortality, medical therapy and pulmonary rehabilitation may benefit these patients. Lung transplantation should be considered in those with end-stage disease.

Histopathological Grading of Oral Mucosal Chronic Graft-versus-Host Disease: Large Cohort Analysis.

Graft-versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n=112). Oral mucosal biopsy sections (n=303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosin-stained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n=47) and healthy (n=15) specimens. Remaining biopsy specimens (n=199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P < .001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease.

Embryonic rhabdomyosarcoma of the petrous bone in a child: a case report

Rhabdomyosarcoma (RMS) is a cancer of skeletal muscle origin, and the second most common soft tissue sarcoma encountered in childhood. The head and neck are common sites though the temporal bone is rare. Rhabdomyosarcoma represents 3.5% of all malignancies in children aged 0-14 years, with approximately 250 new cases diagnosed each year. Despite the more intensive management modalities including surgery and combination chemo-radiation, the outcome for patients with metastatic disease remains poor. Here, we report a case of temporal bone Embryonic RMS in a three and half year-old male who was seen at Mulago National Referral Hospital, Kampala in 2016 and describe the clinical, radiological and histopathological presentation of relevance to RMS. Key Words: rhabdomyosarcoma, temporal bone, mesenchymal tissue, parameningeal, chronic suppurative otitis media, multi-modality therapy, Kampala

Relationship between the immunohistological examination and fluorescence visualization of oral squamous cell carcinoma.

Disorders of the oral mucosa are considered easy to diagnose since they can be visualized and examined directly. A change in the color of the oral mucosa reflects histopathological changes and is an important diagnostic parameter. However, the subjective perception of color varies. To determine the extent of resection for oral mucosa conditions, it is necessary to digitize the color and perform objective assessments. In recent years, fluorescence visualization devices and analysis software that measure tissue luminance G have been employed for the identification of oral mucosa diseases. Fluorescence visualization is presumably based on the decrease in epithelial flavin adenine dinucleotide content and luminance G values due to the destruction of collagen cross-links [fluorescence visualization loss (FVL)]. However, cases with differences between luminance values and histopathological presentation exist. Therefore, additional factors may affect fluorescence visualization. The present study used a portable, non-contact oral mucosa fluorescence visualization device for luminance measurements in seven patients with oral squamous cell carcinoma. Furthermore, Picro-Sirius Red and immunohistochemical staining were performed for CK13, CK17, Ki67, p53 and E-cadherin in the FVL(+) (lesion) and FVL(−) (resection stump) areas to elucidate the principle of fluorescence visualization. Fluorescence was significantly lower in the FVL(+) than in the FVL(−) areas, and the mean luminance G value was 56. The Picro-Sirius Red stain revealed collagen destruction in the FVL(+) areas but no collagen disruption in the FVL(−) areas. CK13 was negative in the FVL(+) and positive in the FVL(−) areas, whereas the opposite pattern was observed for CK17. In the FVL(+) area, p53 staining was positive. E-cadherin expression was enhanced in the FVL(−) areas and reduced in the FVL(+) areas. Furthermore, the luminance G value tended to be lower in cases with weaker E-cadherin staining. The aforementioned results suggest that decreased E-cadherin expression may be a factor that regulates fluorescence visualization.

Acneiform Presentations of Folliculotropic Mycosis Fungoides.

Folliculotropic mycosis fungoides (FMF) is a variant of cutaneous T-cell lymphoma that has clinical overlap with a variety of inflammatory follicular unit disorders. However, we describe distinctive presentations of FMF with acneiform features that can be diagnostically challenging, leading to diagnostic delay. To highlight the importance of histopathologic and immunohistochemical evaluation for diagnostic confirmation of presumed inflammatory follicular unit-based disorders that are unusual in presentation or unresponsive to standard therapies. A cross-sectional retrospective study of 5 consecutive patients with a histopathologic diagnosis of FMF was conducted. The clinical, histopathologic, immunophenotypic, and molecular genetic features of cases are presented. We describe 5 patients with clinical and histopathologic presentations of FMF masquerading as hidradenitis suppurativa, furunculosis, or acne vulgaris (age range 34-66 years, 4:1 female to male). Clinical morphologies included open and closed comedones, inflammatory pustules, papules and nodules, follicular papules with keratotic plugging, cysts, and scarring involving the face, trunk, and intertriginous areas. All patients failed to respond to standard therapies, including topical and oral antibiotics, topical and oral retinoids, or topical corticosteroids, before receiving the diagnosis of FMF. Lesional skin biopsies showed a perifollicular CD4-positive T-lymphocytic infiltrate with pilotropism, intrafollicular mucin deposition, foreign-body granulomatous inflammation, acute inflammation, and follicular epithelial necrosis. None had concurrent systemic mycosis fungoides. Small retrospective cohort study. We present these cases to expand the clinical and histopathologic spectrum of FMF that may strikingly resemble acneiform disorders and to highlight the importance of diagnostic reconsideration with histopathologic evaluation.

Chemical-Associated Vitiligo

An otherwise healthy man in his 40s presented with white macules and patches that appeared on his skin several years ago. Initially, he noticed asymptomatic white discoloration on the ventral aspect of wrists, with subsequent involvement of thehead and neck. He had no relevant medical, drug, or family history, except for thyroid dysfunction in his mother. He worked in a laundry facility, with frequent exposure to detergents. Examination revealed well-demarcated hypopigmented patches without erythema or scaling on the ventral forearms (Figure 1). One patch on the occipital area scalp showed white discoloration of the associated hair (Figure 2). Wood's lamp examination showed no accentuation. Based on the patient’s history of exposure by frequently implicated chemicals, as well as the morphology and distribution of skin lesions, a diagnosis of chemical-associated vitiligo was made.Figure 2Well-defined coalescing hypopigmented patches on ventral forearm.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Chemical-associated vitiligo, an acquired disorder that presents with hypo- or depigmented patches, is thought to be induced by repeated exposure to specific chemicals.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Several chemical compounds have been implicated, most of which contain phenol groups in their chemical structure. Because the phenol group constitutes a part of the amino acid tyrosine, the precursor of melanin, it has been hypothesized that phenol-containing compounds act as tyrosine analogs when applied to the skin, thereby interfering with melanogenesis.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar Others have hypothesized that depigmenting chemicals produce metabolites that are toxic to melanocytes or overwhelm the melanocyte ability to withstand oxidative stress.2Boissy R.E. Manga P. On the etiology of contact/occupational vitiligo.Pigment Cell Res. 2004; 17: 208-214Crossref PubMed Scopus (207) Google Scholar In cases of occupational exposure, as in our patient, the hands and forearms are frequently involved. However, some reports demonstrated that lesions could appear in remote areas: that is, those not in direct contact with chemical substances.3Bonamonte D. Vestita M. Romita P. Filoni A. Foti C. Angelini G. Chemical leukoderma. dermatitis: contact, atopic, occupational, drug.Dermatitis. 2016; 27: 90-99Crossref PubMed Scopus (16) Google Scholar This observation has led to invocation of the autoimmune theory, proposing that chemical-induced stress in melanocytes initiates an autoimmune response, leading to their destruction. Subsequently, this immune response can affect other melanocytes in distant regions that are not directly in contact with the chemical.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar By contrast, idiopathic vitiligo commonly affects the periorificial areas, nipples, and genitals. Chemical-associated vitiligo represents a diagnostic challenge, as it is often difficult to differentiate it from idiopathic vitiligo based on the clinical as well as the histopathological presentation.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar The presence of 3 out of the following 4 criteria are considered sufficient for establishing the diagnosis of chemical-associated vitiligo: acquired vitiligo-like depigmented lesion(s), history of repeated exposure to specific chemical compounds, patterned vitiligo-like macules at site of exposure, and confetti macules.4Ghosh S. Mukhopadhyay S. Chemical leucoderma: a clinico-aetiological study of 864 cases in the perspective of a developing country.Brit J Dermatol. 2009; 160: 40-47Crossref PubMed Scopus (69) Google Scholar Thorough history taking is essential to diagnose chemical-associated vitiligo and identify the possible culprit. Presumably, chemical-associated vitiligo does not confer the same increase in associated autoimmune conditions as does idiopathic vitiligo, although this is not well studied.5Gill L. Zarbo A. Isedeh P. Jacobsen G. Lim H.W. Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: a cross-sectional study.J Am Acad Dermatol. 2016; 74: 295-302Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar In many cases, strict avoidance of the offending chemical agent allows the condition to self-resolve. Moreover, chemical-associated vitiligo tends to respond better to skin-directed treatments than idiopathic vitiligo.1Harris J.E. Chemical-induced vitiligo.Dermatol Clin. 2017; 35: 151-161Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar

GFAP IgG associated inflammatory polyneuropathy

BackgroundGFAP (glial fibrillary acidic protein)-IgG is predominantly associated with meningoencephalomyelitis, and neuropathy presentations are rare. MethodsWe reviewed clinical, electrodiagnostic and histopathological presentations of GFAP-IgG associated peripheral neuropathy. ResultsWe identified six cases, five of whom had peripheral neuropathy as the initial presentation. Acute/subacute polyradicluoneuropathy or proximal nerve involvement was a common presentation. Three had demyelinating neuropathies on electrophysiological studies. Nerve biopsies (n = 2) demonstrated T-cell predominant perivascular inflammatory collections, and all patients with clinical follow up responded favorably to immunotherapy. ConclusionGFAP neuropathy represents a potentially treatable immune-mediated neuropathy and can occur with or without co-existing meningoencephalomyelitis.

Nasopharyngeal Carcinoma Profile in dr. Cipto Mangunkusumo Hospital Year 2013

Background: Nasopharyngeal carcinoma (NPC) remains as a health burden in Indonesia. It is one of most common cancers in Indonesia, with an overall incidence estimated at 6.2/100,000 or 12,000 new cases per year. Unfortunately, many of these cases are unregistered due to several factors, such as lack of national cancer registry. In most developing countries, cancer registration often begins in hospitals. Hospital-Based Cancer Registry (HBCR) provides the initial and major source of information on patients that leads to the set-up of a population-based registry. Materials and Methods: This was a descriptive retrospective study of all registered NPC patient in HBCR, from January-December 2013. All registered NPC patients in HBCR in the year 2013 is included. Results: There were 299 NPC patients, with a male-to-female ratio of 2.4:1. Median age was 47 years old, with majority of age between 40-49 years old (27.4%). Most common type of histology was undifferentiated NPC (85%). Most patients presented with locally advanced disease, with majority of stage IVA (33.9%). Chemoradiation remained as standard treatment for locally advanced NPC (84.1%). Conclusion: Demographic data of patients, such as age and sex, are consistent with previous studies. Whereas racial distribution was not parallel with previous studies, maybe due to its lack of available data. Moreover, most common histopathology type and presentation was undifferentiated NPC and patients with Stage III to IV cancer.

Clinicopathological Presentation and Management of Penile Schwannoma

Patients with penile schwannoma are rare and usually with variant presentations. No evidence-based clinical guideline exists for diagnosis or treatment. To put schwannoma into differential diagnoses of benign soft tissue lesions in the penis is important. To analyze and categorize clinical, histopathological, and radiological presentations and apply possible explanation on several fields of penile schwannoma. We collected the English literature through the PubMed database of the National Library of Medicine up to October 2019. A newly diagnosed case in Chang Gung Memorial Hospital, Taiwan, was also included. This study categorized lesion locations into the penile body or shaft, glans, or penile root, dorsal or ventral. The main outcome measure was to demonstrate clinical, pathological, ultrasonography, and MRI manifestations of penile schwannoma and perform immunohistochemistry staining that has not been performed among penile schwannomas. We collected 40 cases. Data were arranged in tables. Clear descriptions were added on several fields of penile schwannoma in detail in Discussion. Penile schwannomas are mostly located at the penile shaft and dorsum of the penis. Dyspareunia is the most reported complaint for sexual dysfunction. This study is the first study in the world to document the expressions of calretinin, SOX10, glial fibrillary acid protein, D2-40 (podoplanin), and cytokeratin AE1/AE3 in penile schwannoma and claims magnetic resonance imaging and pathologic presentations of penile schwannomas are synonymous with schwannomas from head to toe. The current patient may be the first to present with penile schwannoma with schwannomatosis. Huang LC, Wang HZ, Chu YC, etal. Clinicopathological Presentation and Management of Penile Schwannoma. Sex Med Rev 2020;8:615-621.

Management of a case of diffuse sclerosing osteomyelitis

Definitively diagnosed disease-directed therapy leads to the rapid resolution of clinical illness and decreases the chances of developing chronic ailments. Appropriate diagnosis is crucial in initiating such therapies which can be made straightforward with the assistance of modern diagnostic aids. Osteomyelitis is an inflammatory disease of the bone and its marrow contents. This disease can have multifarious clinical and histopathologic presentations. Osteomyelitis of the jaws has proved to be a challenging condition to effectively diagnose, treat, and cure. However, there are various diagnostic aids which help in the identification of the condition. The diagnosis is usually based on a thorough evaluation of the patient history and clinical presentation, imaging techniques, culturing, and histologic analysis. Cone-beam computed tomography (CBCT) has proved to emerge as a promising diagnostic aid in relation to osteomyelitis. CBCT offers different views that give a clear insight into the extent of involvement of the disease. Treatment of this condition includes two lines of management – conservative approach and surgical approach. The conservative approach includes the use of antibiotics, hyperbaric oxygen therapy which improves the availability of antibiotics at the localized site, especially with the sclerosing variant. Surgical interventions are usually confined to the extraction of extremely mobile teeth, debridement of fragments of bone, and incision and drainage of fluctuant areas. Additional surgical procedures are considered if the infection persists, and these include sequestrectomy, saucerization, decortication, or resection followed by reconstruction. A case of diffuse sclerosing osteomyelitis arising from nonvital teeth managed using the surgical approach is presented here.

Propranolol therapy for the management of oral lobular capillary hemangioma in a 2-year-old preschooler: A case report and review

Lobular capillary hemangioma (LCH), a histological variant of pyogenic granuloma (PG) is an inflammatory hyperplasia commonly seen on oral mucosa as a reaction to local irritants, trauma or hormonal influences. The term “PG” is a misnomer as it is neither pus filled nor representative of a granuloma histologically. It is an inflammatory lesion composed of proliferating vascular, fibrous, and inflammatory tissue. The benign tumor has varied clinical and histopathological presentations and occurs frequently on the gingiva in the oral cavity. The article presents a case report where 2-week propranolol therapy was used to manage oral LCH (with a rare site of presentation) in a 2-year-old preschooler with a 9-month follow-up showing no recurrence followed by review of literature.

Necrotizing sialometaplasia: a case report of a non-ulcerated histopathological presentation

A 27-year-old woman presented with the chief complaint of severe pain in the palate region, which had been present for two months. Upon examination, she was found to have a firm, non-ulcerated nodule measuring about 2.5cm at the palatal junction. Incisional biopsy was recommended because the clinical differential diagnosis was mucoepidermoid carcinoma or squamous cell carcinoma. Anatomopathological examination revealed squamous metaplasia of the salivary gland ducts with preservation of the lobular architecture. Immunohistochemistry showed metaplastic ducts with low reactivity for p53 and Ki67, as well as positivity for CK AE1/AE3, CK7, p63, S-100, and SMA. The final diagnosis was necrotizing sialometaplasia. No treatment is required for this disease. Thirty-nine days after biopsy, total remission was observed with no signs of relapse after two years.

Comparison of enzyme-linked immunosorbent assay and immunofluorescence test for determination of anti-Encephalitozoon cuniculi antibodies in sera from rabbits with different clinical and histopathological presentations

ABSTRACT Encephalitozoon cuniculi is a microsporidian that infects rabbits resulting in a varied pathology of the nervous, renal, and ocular tissues. Serology based studies using different methods have been conducted indicating a high seroprevalence worldwide in pet rabbits. While qualitative results are not especially helpful in the diagnosis of this infection, quantitative titers can have increased predictive value. In the current study, results of enzyme-linked immunosorbent assay (ELISA) and immunofluorescence test methods were compared using banked samples from rabbits with confirmed infection and clinically normal rabbits. Pearson's analysis found good and significant correlation (R = 0.56, P = 0.0002). Bland Altman analysis demonstrated the methods were similar but not equivalent. The sensitivity ranged from 0.79 to 0.84 and the specificity was 1.00 for both assays. Anti-E. cuniculi IgM titers were also determined by ELISA to be an independent measure from IgG (R = 0.31, P = 0.06) with a sensitivity of 0.24 and specificity of 1.00. In total, these results confirm an agreement in the detection of IgG antibody by two different methods conducted at laboratories in the United States and Austria that are involved in research and clinical diagnostic testing of this agent.

Sequestered Disc Herniation in a Dog

Background: Dogs are frequently affected by intervertebral disc degeneration, a structural failure associated with changes accelerated by aging. Disc degeneration may occur in the presence or absence of clinical signs, which are variable and common to other spinal cord diseases and therefore early diagnosis is crucial to a successful outcome. Treatment may be conservative or surgical according to severity of the clinical signs and should be combined with a rehabilitation protocol. Prognosis depends on the location of the spinal cord compression, volume and velocity of the disc material herniation and time between initial clinical signs, definitive diagnosis and therapeutic approach. Case: A nonchondrodystrophic 14-year-old dog with acute clinical manifestation of paraparesis and proprioceptive deficit in hind limbs was submitted to myelography examination. There was contrast column deviation in the T13-L1 region, determining spinal compression, and spondyloses were also noted in several thoracolumbar vertebrae. Hemilaminectomy was performed with complete removal of the compressor fragment. Histological analysis confirmed the presence of fibrocartilaginous material that corresponds to the part of the annulus fibrosus. The kidnap of the fragment was characterized by loss of continuity with the remaining disk. In these cases, magnetic resonance imaging does provides the definitive diagnosis, since neoplasm, arachnoid cysts and abscesses may be remaining differential diagnosis. Therefore, surgical approach followed by histopathological analysis of the obtained material are necessary to confirm the diagnosis.Discussion: The present report differs from most cases of disc herniation because it is a thoracolumbar lesion with an acute manifestation of significant neurological deficit in an elderly dog of non-chondrodystophic breed. Also, material of the free fibrous annulus itself in the medullary canal is not a common histopathological presentation of disc extrusion usually composed by nucleus pulposus. After neurolocalization of the lesion by clinical neurological examination, the radiographic evaluation shall precedes the myelography, since this is contraindicated when there is suspicion of discoespondylitis, fracture, dislocation or vertebral subluxation, which had not yet been discarded. Even if the MRI is performed, in the cases of a sequestered fragment, it still remais differential diagnoses include arachnoid cysts, discoespondylitis, hematomas, abscesses and neoplasms, including metastases, so only surgical approach to obtain material for histopathological analysis may provide definitive diagnosis. According to the histopathological examination, the herniated material had a fibrocartilaginous characteristic: several concentric fibrous blades, composed of collagen and fibrocartilage, thus characterizing the herniated material as a fragment of the fibrous ring. When removed from the vertebral canal, the contents did not show resistance, being withdrawn completely and without continuity with its origin intervertebral disc. The patient's disc herniation could not be classified as a disc protrusion because this affection is described as a projection of the fibrous annulus towards the vertebral canal due to the partial rupture of fibers and mineralization of the nucleus pulposus, without discontinuity of some content. Disc protrusion shows mild and progressive signs, except if there is complete rupture of the fibrous ring as can be seen in the sequestered disc herniation. Although infrequent, elderly animals of non-chondrodisiotic races may show acute signs of neurological deficits. Sequestrated disc herniation may mimic other lesions, requiring a surgical approach to obtain material for histopathological analysis to confirm the diagnosis.

P.243Dusty core disease (DuCD): a novel morphological hallmark for RYR1 recessive myopathies

We recharacterized the RYR1-recessive morphological spectrum by a large study performed on 54 muscle biopsies from a of 48 genetically confirmed patients, using histoenzymology, immunohistochemistry, and ultrastructural studies. We also analysed the level of RyR1 expression in patients' muscle biopsies. We defined "dusty cores" the irregular areas of myofibrillar disorganisation characterised by a reddish-purple granular material deposition with uneven oxidative stain and devoid of ATPase activity, which represent the characteristic lesion in muscle biopsy in 54% of patients. We named Dusty Core Disease (DuCD) the corresponding entity of congenital myopathy. Dusty cores had peculiar histological and ultrastructural characteristics compared to the other core diseases. DuCD muscle biopsies also showed nuclear centralization and type1 fibre predominance. Dusty cores were not observed in other core myopathies and centronuclear myopathies. The other morphological groups in our cohort of patients were: Central Core (CCD: 21%), Core-Rod (C&R:15%) and Type1 predominance "plus" (T1P+:10%). DuCD group was associated to an earlier disease onset, a more severe clinical phenotype and a lowest level of RyR1 expression in muscle, compared to the other groups. Variants located in the bridge solenoid and the pore domains were more frequent in DuCD patients. In conclusion, DuCD is the most frequent histopathological presentation of RYR1-recessive myopathies. Dusty cores represent the unifying morphological lesion among the DuCD pathology spectrum and are the morphological hallmark for the recessive form of disease.

Evaluation of the acute and 28-day sub-acute intravenous toxicity of α-l-guluronic acid (ALG; G2013) in mice

α-l-Guluronic acid (ALG; G2013) has been previously introduced as a new anti-inflammatory agent with promising therapeutic effects. Thus, in the present study, we aimed to evaluate the acute and sub-acute toxicity of ALG through intravenous (i.v.) administration in Balb/C mice. ALG was administrated i.v. to the mice with doses of 300, 600, and 1000 mg/kg of body weight to investigate acute toxicity (single dose) and with doses of 25, 50, and 100 mg/kg of body weight to sub-acute toxicity study (daily injections for a period of 28 days). The mortality rate, food and water intake, behavior, body weight, gross necropsy, hematological and biochemical parameters as well as histopathological presentations of the vital organs (kidneys, liver, lungs, spleen, and heart) were examined in treated groups and compared to the healthy controls. The results of both acute and sub-acute studies showed that i.v. administrations of ALG did not affect the investigated parameters in both sexes, indicating that the LD50 of ALG was higher than 1000 mg/kg of body weight. As no difference was observed in toxicity profiles of investigated doses, no-observed-adverse-effect-level for i.v. administration of ALG in the sub-acute study was greater than 100 mg/kg body weight in both female and male mice. According to the finding, i.v. administration of ALG did not lead to any clinical sign in abovementioned doses, suggesting that ALG was well tolerated up to 1000 mg/kg. These pre-clinical findings support the application of ALG in the future clinical trials.

Clinico-pathological considerations in a 48-years-old female with acute kidney injury: is it lupus nephritis, ANCA-associated vasculitis or something else?

BackgroundThe value of ANCA positivity in the setting of systemic lupus erythematous and their pathogenicity remains uncertain.Case presentationWe report the case of a 48-year-old female with rapidly progressive kidney failure, arthro-myalgia and weight loss. Auto-immune screening showed anti-dsDNA antibodies, complement consumption and triple ANCA positivity. A first kidney biopsy done at presentation highlighted class IV-G glomerulonephritis with elective extra-capillary involvement and mainly C1q glomerular deposition at immunofluorescence study. After three months of a regimen combining steroids and cyclophosphamide, a second biopsy was performed and showed class IV-G glomerulonephritis with mainly endocapillary proliferation.ConclusionThis case is atypical in view of immunological profile and kidney histopathological presentation and evolution and gives rise to discussion in view of recent data on ANCA value in lupus nephritis, and suggests that different auto-immune pathways may be involved in lupus nephritis.

Cutaneous pseudolymphoma-A review on the spectrum and a proposal for a new classification.

Cutaneous pseudolymphomas (PSLs) belong to a group of lymphocytic infiltrates that histopathologically and/or clinically simulate lymphomas. Different causative agents (e.g., Borrelia sp., injected substances, tattoo, arthropod bite) have been described, but in many cases no cause can be identified, hence the term idiopathic PSL. Clinicopathological correlation is important to make the diagnosis. Four main groups of cutaneous PSL can be distinguished based on histopathologic and/or clinical presentation: (a) nodular PSL; (b) pseudo-mycosis fungoides (pseudo-MF) and simulators of other CTCLs; (c) other PSL (representing distinct clinical entities); and (d) intravascular PSL. This article gives an overview of the histopathologic and clinical characteristics of cutaneous PSLs and proposes a new classification.

Clinical and histopathological presentation and successful treatment with ciclosporin for canine sarcoidosis: a case report

Sarcoidosis is a granulomatous disease histologically characterized by naked granulomas in various mammals. Canine sarcoidosis is a rare disease which can cause nonpruritic papule, plaques and nodules on the trunk, neck, face and ear; it is usually treated with corticosteroids. To date, there are no published reports on alternatives to corticosteroids treatment. To report a case of canine cutaneous sarcoidosis successfully treated with oral ciclosporin. An 11-year-old beagle dog was presented with multiple pleomorphic plaques on the lateral thighs and dorsal trunk. Skin punch biopsy specimen were collected and analysed via routine histological examination and immunohistochemistry. After 14weeks of oral ciclosporin treatment, repeat skin biopsy specimens were collected. Histopathological examination revealed noncaseating epithelioid cell granuloma formation in the dermis. Dermal epithelioid cells were positive for CD18 and Iba1, but not for CD3, CD20 and E-cadherin based on immunohistochemistry findings. Acid-fast bacteria, fungi and Leishmania spp. were not detected by special stains, culture or polymerase chain reaction. An initial two week treatment with immunosuppressive doses of oral prednisolone and doxycycline was not effective. Skin lesions were almost in remission after 14weeks of oral ciclosporin treatment without adverse events. Histologically, the dermal granulomatous lesions regressed and were replaced by fibrous tissues after ciclosporin treatment. This case report describes the clinical and histopathological presentation including immunohistochemistry and treatment outcome of a case of canine sarcoidosis Ciclosporin may be an effective alternative to corticosteroids for treating canine sarcoidosis.