Atypical Features Research Articles

#2265 The challenge of renal biopsy in diabetic patients: evaluation of a single center large cohort from North-West Italy

Abstract Background and Aims Diabetic kidney disease is one of the most severe long-term complications of diabetes. Currently, the international guidelines suggest diagnosis of diabetic nephropathy to be achieved on a clinical ground only. However, in the heterogeneous cluster of different conditions putatively co-existing with diabetes, renal biopsy is a unique tool for an accurate diagnosis and a guide for patient management. The aim of the study was to retrospectively analyze monocentric case history of kidney biopsies performed in diabetic patients over a period of 10 years. Patient's data were collected both at the time of histological examination and during follow-up. Method Data of renal biopsies (RB) performed in patients with diabetes mellitus from 1st January 2014 to 31th July 2023, were collected. Patient identification was performed by reviewing clinical histories and histopathological charts. Data on the indication for RB were collected from the medical report of the hospitalisation when the procedure was performed or from the visit when the indication was given. Atypical features were categorized according to an adaptation of the 2007 KDOQI guidelines for diabetes and chronic kidney disease. The significance of baseline differences was determined by the chi-squared test, Fisher's exact test or the unpaired t-test, as appropriate. Significance of univariate analysis were confirmed through the use of multivariate analysis. Correlation analysis, linear regression and Cox regression were also performed. A two-sided P-value <0.05 was statistically significant. All statistical analyses were performed using SPSS version 26.0 (IBM, Armonk, NY, USA). Results Among 1990 patients (pts) who underwent kidney biopsy during the study period, 297 had type 1 or type 2 DM (14.9%) and were therefore included in the study, regardless of diagnostic suspicion and histological findings. Histological examination revealed diabetic nephropathy (DN) in 112 cases (group 1), DN associated with another kidney disease in 56 cases (group 2) and nondiabetic renal diseases alone in the remaining 129 cases (62%) (group 3). In group 2 the kidney disease most frequently associated with DN was focal and segmental glomerulosclerosis, FSGS (24/56 pts) followed by IgA nephropathy, IgAN (14/56 pts). In this population the histological examination led to specific therapeutic indications in 22 patients. In group 3 the most frequently observed kidney disease was FSGS (37/112 pts) followed by ANCA-vasculitis (14/112 pts), membranous nephropathy (14/112 pts) and IgAN (10/112). In this population, histological examination led to a specific therapeutic indication in 67 pts. To determine predictors for histopathological diagnosis of DKD, we ran a logistic regression model. The covariates used in this model were the duration of diabetes, presence of retinopathy, hypertension, serum creatinine values, eGFR values and 24-hours proteinuria. None of them was found to be statistically significant. It should also be noted that 47 out of 112 pts (42%) with diabetic nephropathy had no retinopathy. In contrast, 9 pts (7%) with histological evidence of NDRD had diabetic retinopathy. 215 out of 297 pts had a follow-up of at least 6 months. During a mean follow up of 41.6±31.8 months, 53 pts (24 in group 1, 15 in group 2 and 14 in group 3) reached end stage kidney disease (16.5 months). In our population the presence of DN associated with another biopsy-proven nephropathy was especially prevalent. Having double nephropathy conferred a relative risk-RR for dialysis of 1.8089 (95% CI 1.0094 to 3.2415, P = .0464). Conclusion To our knowledge this is the largest cohorts of diabetic patients receiving renal biopsy even reported in a Western country. Our data proved kidney biopsy not to be an academic exercise in diabetic pts. Clinical and laboratory features do not predict histologic findings. Renal biopsy allowed the identification of unsuspecting nondiabetic kidney injuries and double nephropathies, which could be susceptible to different outcomes, and paved the pathway for treatment of potentially manageable histological changes.

#1148 Polycystic kidney disease—beyond PKD1 and PKD2

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a common form of hereditary kidney disease, with an estimated prevalence of 1 out of 1000 individuals worldwide. Although its key clinical manifestation is progressive formation and growth of renal cysts, extra-renal manifestations such as hypertension, cysts in other organs, cardiac valve disease and cerebral aneurysms reflect that it is a systemic disorder. Classical ADPKD is associated with heterozygous PKD1 and PKD2 pathogenic gene variants. Less common involved genes that may present as atypical cystic disease include GNAB, DNAJB11 and more recently ALG5/9. Genes associated to syndromic ciliopathies such IFT140 and OFD1 have also been related to atypical ADPKD. Literature reports that 10% patients with ADPKD phenotype will have de novo pathogenic variant. Around 7% of families have negative genetic testing despite clinical phenotype. Failure to consider broader genetic panels or exome sequencing if available may lessen diagnostic yield. Method We performed descriptive analysis on patients with no family history cystic disease and negative PKD1/PKD2 gene testing in our hereditary nephropathy clinic. Atypical cystic disease was defined as non-enlarged kidneys despite multiple cysts and asymmetrical kidney cyst affection in terms of size and quantity, determined through imaging studies. Results From January 2019 until December 2023, n = 39 genetic tests were performed in patients with cystic disease phenotype, n = 28 (13%) without family history. Twelve patients (31%) had positive PKD1/PKD2 variants analysed by PCR long range multiplex. Fig. 1 represents the genetic test results in the remaining patients (n = 16) with cystic disease phenotype and no family history. Positive genetic testing was obtained in n = 7 (43%). Ten patients (63%) presented features of atypical cystic disease. These had a median referral age of 48 years (IQR 34-58), n = 3 (30%) male. Three causal genetic variants were identified (1 with variants in IFT140 and 2 in OFD1 gene), the remaining with negative genetic test result. Patients without atypical features had a median age of referral 55 years (IQR 38-58), n = 4 (60%) were male. Variants in GANAB, LRP5 and PKHD1 genes were identified in this subgroup. Extra-renal manifestations were seen in in 70% and 50% of patients with and without atypical cystic disease, respectively. The main extra-renal manifestation encountered was hepatic cysts. One patient with a pathogenic OFD1 variant presented syndactyly. Conclusion In recent years, growing knowledge in the field and identification of genes involved in ciliopathies associated with atypical forms polycystic kidney disease have allowed for genetic diagnosis of non-PKD1/PKD2 forms. The identification of new genes associated with atypical forms of polycystic kidney disease has called attention to a potential overlap between polycystic and tubulointerstitial phenotypes. With growing knowledge in genetics leading to improvement of cystic kidney disease panels and increased experience in exome sequencing, diagnostic yield is likely to increase in the coming years. Genetic basis of disease is important considering possibility of avoiding primary transmission through pre-implantatory genetic diagnosis but also in the management and diagnosis of gene-specific systemic manifestations.

An Unusual Case of an Intradiploic Arachnoid Cyst of the Orbit.

This study reported a case of an arachnoid cyst of the sphenoid bone causing orbital signs and symptoms in a 58-year-old man with progressive proptosis and nonspecific discomfort in the OS. Orbital MRI showed a 3-cm homogeneous cyst within the left greater wing of the sphenoid bone. To the best of our knowledge, this is the first report of an intradiploic arachnoid cyst in the sphenoid bone with atypical radiological features, causing clinical symptoms, and managed through an eyelid approach, achieving a complete resolution with no complications.

P16 Expression in Multinucleated Stromal Cells of Fibroepithelial Polyps of the Anus (FEPA): A Comprehensive Review and Our Experience

Fibroepithelial polyps of the anus (FEPA) are a common benign polypoid proliferation of the stroma covered by squamous epithelium. They are also an often-overlooked part of pathological practice. Currently, immunohistochemistry (IHC) for p16 is the only recommended test for anal intraepithelial neoplasia, but the expression of p16 in stromal multinucleated atypical cells in FEPA has not been described. We aimed to evaluate the expression of p16 in stromal multinucleated atypical cells in FEPA and its role as a diagnostic biomarker to determine the origin of the atypical multinucleated cells in the stroma of FEPA and to rule out the possibility of a neoplastic process. Therefore, we researched a series of 15 FEPA in middle-aged patients histologically and by IHC. Examination of the subepithelial connective tissue from the FEPA showed bizarre, multinucleated cells, while their causal relationship with human papillomavirus (HPV) infection was rejected. In all cases, these cells showed mild to moderate atypical nuclear features and positive expression for p16, while the overlying squamous epithelium was negative. We concluded that FEPA are benign lesions in the stroma where mononuclear and multinucleated (sometimes atypical) cells showing fibroblastic and myofibroblastic differentiation can be found. Nevertheless, we believe that these cells have a practical diagnostic significance, although sometimes the presence of giant cells is difficult to establish, especially in the inflammatory context. The histological similarity between FEPA and normal anal mucosa supports the hypothesis that FEPA may represent the reactive hyperplasia of subepithelial fibrous connective tissue of the anal mucosa.

Contribution of Imaging in the Hydatid Cyst of Soft Tissues in the Thigh: A Case Report and Literature Review

Hydatid cysts in soft tissues remain a rare occurrence, even in endemic regions. This study underscores the crucial importance of imaging modalities for positive diagnosis and topography, providing optimal guidance for effective management strategies. In this article, we present a case of soft tissue hydatidosis in the thigh, directly explored through magnetic resonance imaging (MRI), complemented by soft tissue ultrasound. The observed mass contained vesicles, localized in the thigh. The diagnosis of hydatidosis suggested by ultrasound was confirmed by MRI. A curative surgical intervention was performed on our patient. The diagnosis of soft tissue hydatidosis can be established when ultrasound and/or MRI reveal a multivesicular appearance. MRI proves to be the most useful imaging modality in cases of atypical or pseudo-solid lesions. The peri-cystic enhancement serves as an indicative feature of soft tissue hydatidosis compared to other locations. The study emphasizes the rarity of muscular localization of hydatid cysts and highlights the crucial importance of radiological, surgical, and preventive diagnostic approaches in managing this pathology. The heightened sensitivity of MRI in cases of atypical ultrasound features underscores its central role in the contemporary management of this complex condition, enhancing both diagnostic precision and treatment planning.

Melorheostosis With Uniform Rib Thickening.

A 16-year-old girl presented with left chest pain. Radiography and CT revealed localized abnormal calcification in the left sixth rib and sixth thoracic vertebra. Bone scintigraphy confirmed abnormal uptake of 99mTc in the same area. An open biopsy of the sixth rib was performed, leading to the diagnosis of melorheostosis. This case showed uniformly thickened calcification throughout the rib, unlike the typical "dripping candle wax" radiography finding associated with melorheostosis. This case implies the importance of open biopsy for diagnostic confirmation in cases with atypical imaging features.

Proliferating inverted follicular keratosis of genital skin: Case series of a challenging variant.

Inverted follicular keratosis (IFK) is a benign cutaneous epithelial tumor typically presenting as a small papule on the head and neck. We have encountered deep endophytic tumors on genital skin with some characteristics of IFK but also atypical features, raising concern for squamous cell carcinoma (SCC). Four such tumors were identified in our database. Histopathologic analysis and ancillary studies were performed. All patients were young women who presented with a solitary 0.5-1.0 cm lesion on the vulva, perineum, or inner buttock. Each showed a squamous proliferation arising from the epidermis, with endophytic growth that was deep and bulbous but not infiltrative. The tumor lobules contained eosinophilic keratinocytes, forming numerous squamous eddies. Small irregular spaces and dyskeratotic cells were frequently found. Nuclear pleomorphism was minimal to absent. All demonstrated wild-type p53 expression and lack of p16 block positivity. In situ hybridizations for human papillomavirus were negative. None of the three cases with follow-up data showed evidence of recurrence. The absence of infiltrative growth or significant pleomorphism, the presence of numerous squamous eddies, the reassuring immunoprofile, and the lack of evidence of recurrence support a variant of IFK and speak against SCC. We propose the term "proliferating IFK" to highlight the florid squamous proliferation. Recognition of this unusual variant would avoid overdiagnosis of SCC.

A founder mutation in CA5A causing intrafamilial and interfamilial phenotypic variability in a cohort of 18 patients with carbonic anhydrase VA deficiency

AbstractCarbonic anhydrase VA (CA‐VA) deficiency is a rare cause of hyperammonemia caused by biallelic mutations in CA5A. Most patients present with hyperammonemic encephalopathy in early infancy to early childhood, and patients usually have no further recurrence of hyperammonemia with a favorable outcome. This retrospective cohort study reports 18 patients with CA‐VA deficiency caused by homozygosity for a founder mutation, c.59G>A p.(Trp20*) in CA5A. The reported patients show significant intrafamilial and interfamilial variability, and display atypical clinical features. Two adult patients were asymptomatic, 7/18 patients had recurrent hyperammonemia, 7/18 patients developed variable degree of developmental delay, 9/11 patients had hyperCKemia, and 7/18 patients had failure to thrive. Microcephaly was seen in three patients and one patient developed a metabolic stroke. The same variant had been reported already in a single South Asian patient presenting with neonatal hyperammonemic encephalopathy and subsequent development of seizures and developmental delay. This report highlights the limitations of current understanding of the pathomechanisms involved in this disorder, and calls for further evaluation of the possible role of genetic modifiers in this condition.

Epithelioid hemangioma of the acromion causing shoulder pain: a case report.

Epithelioid hemangioma of bone is a rare benign vascular tumor. Because of the locally destructive clinical presentation and the presence of atypical histologic features with increased mitotic activity and necrosis, it is often misdiagnosed as low-grade malignant epithelioid hemangioendothelioma or high-grade malignant epithelioid angiosarcoma. Correct diagnosis through imaging studies and histopathological examination is mandatory to determine the appropriate course of treatment, as the prognosis differs from that of other malignant hemangioma tumors. A 69-year-old male who presented with intractable shoulder pain caused by epithelioid hemangioma in the acromion of the scapula was treated with tumor curettage. This paper reports a good result with a review of the relevant literature.

Invasive Ductal Carcinoma Arising within a Fibroadenoma: A Case Report and Literature Review.

Background: Invasive ductal carcinoma (IDC) is the most common form of breast cancer, frequently presenting independently. Rarely, IDC arises within a fibroadenoma, a benign breast tumor typically associated with younger women. This case report and literature review aim to highlight the diagnostic challenges and clinical implications of finding IDC within a fibroadenoma. Case Presentation: A 36-year-old female patient presented with a dolent palpable mass in the right breast. Initial mammography described normal fibroglandular structures without significant findings. However, subsequent imaging ultrasound identified an 18x14 mm oval formation at the 9 o'clock position in the right breast, categorized as BI-RADS 3. Further histopathological evaluation after a biopsy confirmed the presence of a fibroadenoma with invasive ductal carcinoma, classified as Grade III with perivascular and neural infiltration. Discussion: The coexistence of IDC within a fibroadenoma poses significant diagnostic challenges due to the benign appearance of fibroadenomas on standard imaging modalities. This case emphasizes the need for a thorough evaluation and possible biopsy of fibroadenomas that exhibit atypical features or changes over time. Conclusion: This report underscores the importance of vigilance and comprehensive diagnostic strategies in cases of fibroadenomas, especially in patients with unusual or evolving lesions. The review of literature confirms that although rare, the occurrence of IDC within fibroadenomas can have significant implications for treatment and prognosis.

Invasive meningococcal disease in older adults: current perspectives and call for action.

Invasive meningococcal disease (IMD) is a devastating condition. While most attention is directed towards disease in children and adolescents, IMD poses an important cause of morbidity and mortality in adults ≥60years. While immunization is a critical component of healthy ageing strategies, meningococcal immunization is not routinely offered to older adults. The aim of this review was to summarize clinical and epidemiological aspects of IMD and available immunization strategies, with a particular focus on disease in older individuals, to emphasize the importance of this rather neglected area. An expert working group was established to evaluate clinical and epidemiological data toraise awareness of IMD in older individuals, and develop suggestions to improve the existing burden. Routine child and adolescent meningococcal immunization has substantially reduced IMD in these targeted populations. Consequently, prevalence and proportion of IMD among those ≥60years, mostly unvaccinated, is increasing in developed countries (accounting for up to 25% of cases). IMD-related mortality is highest in this age-group, with substantial sequelae in survivors. IMD due to serogroups W and Y is more prevalent among older adults, often with atypical clinical features (pneumonia, gastrointestinal presentations) which may delay timely treatment. IMD in older adults remains overlooked and greater awareness is required at clinical and societal levels. We encourage clinicians and immunization policy makers to reconsider IMD, with a call for action to remedy existing inequity in older adult access to protective meningococcal immunization.

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

BackgroundCriteria for multiple sclerosis (MS) diagnosis rely upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation. Patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing, even when an individual already meets diagnostic criteria for MS. It is unclear whether ANA serostatus is associated with clinical outcomes in MS. The present study aims to determine if ANA seropositivity in those referred with concern for MS differs in those who meet 2017 revised McDonald criteria compared to those who did not receive a diagnosis of MS. Associations between ANA seropositivity and clinical or radiological phenotype of MS patients are also explored. MethodsThe cohort included people at least 18 years old, referred to our tertiary care MS center with concern for MS (regardless of prior diagnosis) who had an ANA test with known titer completed within one year of first evaluation. Electronic health record (EHR) charts were manually reviewed, and MRIs underwent blinded review by a radiologist with training in neuroradiology. Diagnosis of MS was determined by a neuroimmunologist and was based on 2017 revised McDonald Criteria. Results are reported as odds ratios from multivariable logistic regression analyses adjusted for age, sex at birth, race, smoking history, personal history of comorbid autoimmune conditions, and family history of autoimmunity. Within the MS cohort, similar analytical models were performed to assess association between ANA and clinical and radiological characteristics. ResultsA final cohort of 258 patients was analyzed (out of 542 referrals): 106 nonMS and 152 with MS. There was no association between MS (vs. nonMS) diagnosis and ANA status (ANA positive n = 74) in the multivariable models (OR 1.5, 95 % CI 0.82, 2.72, p = 0.20). Among those with MS, there was no association of ANA seropositivity with the odds of atypical brain MRI features, number of cardinal MRI areas involved, location of MRI lesions, or of having an atypical presentation of first demyelinating event. Black race (OR 2.8, 95 % CI 1.27, 6.26, p = 0.01) and family history of autoimmunity (OR 2.1, 95 % CI 1.09, 3.98, p = 0.03) were independently associated with increased odds of ANA positivity. Within the MS cohort analysis, progressive MS (PMS; vs relapsing-remitting MS), a covariate in the model, appeared to be at higher odds of being ANA positive (OR 3.6, 95 % CI 1.03, 13.05, p = 0.046) but only when assessing mean area of cardinal MS locations. ConclusionsWhile ANA testing does not appear to be useful in distinguishing MS from non-MS, it remains less clear as to whether it may be associated with differences in the clinical course of MS (relapsing-remitting vs progressive). Future studies should aim to systematically evaluate whether those who are ANA positive are more likely, in well-designed and representative prospective cohorts, to be diagnosed with or develop progressive MS. Whether a positive ANA early in MS is associated with increased risk over time of developing or diagnosing another systemic autoimmune disease would also be of interest.

Deep learning models for atypical serotonergic cells recognition

Background:The serotonergic system modulates brain processes via functionally distinct subpopulations of neurons with heterogeneous properties, including their electrophysiological activity. In extracellular recordings, serotonergic neurons to be investigated for their functional properties are commonly identified on the basis of “typical” features of their activity, i.e. slow regular firing and relatively long duration of action potentials. Thus, due to the lack of equally robust criteria for discriminating serotonergic neurons with “atypical” features from non-serotonergic cells, the physiological relevance of the diversity of serotonergic neuron activities results largely understudied. New Methods: We propose deep learning models capable of discriminating typical and atypical serotonergic neurons from non-serotonergic cells with high accuracy. The research utilized electrophysiological in vitro recordings from serotonergic neurons identified by the expression of fluorescent proteins specific to the serotonergic system and non-serotonergic cells. These recordings formed the basis of the training, validation, and testing data for the deep learning models. The study employed convolutional neural networks (CNNs), known for their efficiency in pattern recognition, to classify neurons based on the specific characteristics of their action potentials. Results:The models were trained on a dataset comprising 27,108 original action potential samples, alongside an extensive set of 12 million synthetic action potential samples, designed to mitigate the risk of overfitting the background noise in the recordings, a potential source of bias. Results show that the models achieved high accuracy and were further validated on ”non-homogeneous” data, i.e., data unknown to the model and collected on different days from those used for the training of the model, to confirm their robustness and reliability in real-world experimental conditions. Comparison with existing methods: Conventional methods for identifying serotonergic neurons allow recognition of serotonergic neurons defined as typical. Our model based on the analysis of the sole action potential reliably recognizes over 94% of serotonergic neurons including those with atypical features of spike and activity. Conclusion:The model is ready for use in experiments conducted with the here described recording parameters. We release the codes and procedures allowing to adapt the model to different acquisition parameters or for identification of other classes of spontaneously active neurons.

Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease.

While classic brain MR imaging features of Alexander disease have been well-documented, lesional patterns can overlap with other leukodystrophies, especially in the early stages of the disease or in milder phenotypes. We aimed to assess the utility of a new neuroimaging sign to help increase the diagnostic specificity of Alexander disease. A peculiar bilateral symmetric hyperintense signal on T2-weighted images affecting the medulla oblongata was identified in an index patient with type I Alexander disease. Subsequently, 5 observers performed a systematic MR imaging review for this pattern by examining 55 subjects with Alexander disease and 74 subjects with other leukodystrophies. Interobserver agreement was assessed by the κ index. Sensitivity, specificity, and receiver operating characteristic curves were determined. The identified pattern was present in 87% of subjects with Alexander disease and 14% of those without Alexander disease leukodystrophy (P < .001), 3 with vanishing white matter, 4 with adult polyglucosan body disease, and 3 others. It was found equally in both type I and type II Alexander disease (28/32, 88% versus 18/21, 86%; P = .851) and in subjects with unusual disease features (2/2). Sensitivity (87.3%; 95% CI, 76.0%-93.7%), specificity (86.5%; 95% CI, 76.9%-92.5%), and interobserver agreement (κ index = 0.82) were high. The identified pattern in the medulla oblongata, called the chipmunk sign due to its resemblance to the face of this rodent, is extremely common in subjects with Alexander disease and represents a diagnostic tool that can aid in early diagnosis, especially in subjects with otherwise atypical MR imaging findings and/or clinical features.

Atypical meningiomas compared to other WHO Grade 2 meningiomas: Histological features and prognosis.

To study each atypical feature in atypical meningioma versus other grade 2 meningiomas and its possible relation to recurrence. This is a retrospective study of patients with WHO grade 2 meningioma operated in our institution between 01/2008 and 12/2020. The rate of recurrence, reoperation and readmission were recorded during the follow-up period. A statistical analysis was done to determine the significance of each pathological feature in regard to recurrence. A total of 74 patients were included as WHO grade 2 meningioma with 60 (81%) patients having an AM and 14 (19%) patients with chordoid or clear cell meningioma. The mean age was 51 years±14. The most common location was meningioma abutting the frontal lobe (convexity). Major atypical features were more noted in the AM, however, there was no significant difference between AM and other types of meningioma. Increased Nuclear cytoplasmic ratio and cellularity were found significantly more in AM. The recurrence rate was 16.2%. No specific pathology feature (major or minor) nor the type of Grade 2 meningioma was significantly related to recurrence. The types of WHO grade 2 meningiomas have similar prognosis and recurrence rates. There is no significant difference between the atypical features in indicating a more aggressive nature or risk of recurrence in grade 2 meningiomas.

Ocular Cicatricial Pemphigoid in Young Patients.

The purpose of this study is to report ocular cicatricial pemphigoid (OCP) occurring in young patients. Relevant literature is also reviewed. Medical records of patients aged 30 years or younger who were treated for OCP between August 2021 and May 2023 at a tertiary care eye institute were reviewed. The most common differential diagnoses of cicatrizing conjunctivitis, such as Stevens-Johnson syndrome sequelae, chemical injury, chronic topical/systemic drug use, autoimmune connective tissue disorders, or allergic eye diseases, were ruled out based on clinical history, examination, and the Cicatrizing Conjunctivitis Score described by Shanbhag et al. The diagnosis of OCP was confirmed by positive direct immunofluorescence of oral mucosal and/or conjunctival biopsy in a majority of the patients. Seven patients fulfilled the criteria for a diagnosis of OCP. The mean age at presentation was 21.86 ± 5.25 years (13-28 years). Some of the patients presented with relatively atypical features for OCP such as corneal immune ring infiltrate and bilateral corneal perforation. Six patients exhibited systemic mucosal lesions, and the direct immunofluorescence yield was 85.71%. All patients required aggressive immunosuppressive treatment. OCP is classically described as a rare disease that occurs in old age. This case series highlights the importance of a higher index of suspicion for diagnosing OCP at a younger age. Early administration of immunosuppressive agents can potentially control severe ocular surface inflammation and its sequelae.

Masqueraders Around Disaster: Clinical Features of Scrub Typhus in Fukushima, Japan.

Scrub typhus (ST) is endemic in Fukushima, with the largest number of cases reported in Japan from 2009 to 2010. Although ST is highly treatable, its atypical clinical presentation impedes diagnosis, causing delays in treatment. We review the clinical features of ST in adults from 2008 to 2017 at Ohta Nishinouchi General Hospital in Fukushima, Japan. Fifty-five cases (serotype Karp 24, Irie/Kawasaki 21, Hirano/Kuroki 10) of ST were confirmed via serology based on elevated immunoglobulin (Ig)M and IgG and polymerase chain reaction positivity of eschar samples. The mean age was 69 years, and 64% were female. The case fatality rate was 1.8% (1/55). Approximately 70% of cases (38/55) were not diagnosed as ST upon the initial clinic visit. Inappropriate use of antibiotics was identified in 22% of cases (12/55). In terms of atypical clinical features, 1 or more of the manifestations, fever, rash, and eschar, was absent in 31% of cases (17/55). Approximately 11% of cases presented without eschar (6/55; Karp 1, Irie/Kawasaki 1, Hirano/Kuroki 4). Moreover, severe complications were observed with shock and disseminated intravascular coagulation in 7% of cases (4/55), Thus, while 53% of cases presented with the typical triad (29/55), unusual complications and atypical features occurred in 40% (22/55). Diagnosis of ST becomes clinically challenging in the absence of typical features. In Fukushima, an endemic area of ST, an atypical presentation involving multisystem disease is common.

Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

A rare case of a pharyngeal-cervical- brachial variant of Guillain–Barré syndrome

Abstract: Guillain–Barre syndrome (GBS) is an acute, usually symmetrical, and typically de myelinating polyneuropathy, characterized by progressive, ascending paralysis and areflexia, with or without abnormal sensory function. Therapeutic plasma exchange(TPE) was the first therapeutic modality to impact the disease favorably, and several major randomized controlled trials (RCTs) have confirmed its efficacy. Our case is unique, as this critically ill patient admitted in the intensive care unit (ICU), developed a rare form of GBS, the PCB variant of the disease, and was successfully treated with TPE. The diagnosis of PCB can be challenging due to atypical clinical features but its unique presentation does provide sufficient clues to narrow the differential diagnosis, which is helpful in starting empirical therapy at the earliest. Immunomodulation with plasma exchange and IVIG have been found to improve treatment outcomes; 70%–80% of patients usually have a complete recovery. Early diagnosis is very important in the case of the PCB variant of GBS to enable timely intervention. Diagnosis can be made on history and neurological findings alone.

Eruptive pseudoangiomatosis and parvovirus: exclusive clinical findings

Introduction: Eruptive pseudoangiomatosis (EP) is a rare type of cutaneous exanthema characterized by red angioma-like papules. An association of EP with viral infection has been reported. We herein describe four pediatric patients who showed a new variant of EP-associated rash with atypical clinical features and positivity for parvovirus B19 infection. Case Report: Pediatric patients showed a new variant of EP-associated rash with atypical clinical features and positivity for parvovirus B19 infection by dermoscopy and reflectance confocal microscopy. The papules were localized to the face and characteristic perilesional halo was absent. In all patients, serology revealed evidence of active infection by parvovirus B19. Discussion: Few cases of a facial pseudoangiomatous rash that is related to parvovirus B19 infection and lacks the typical anemic halo have been reported in the literature. Conclusion: These cases provide new data on the clinical spectrum of EP and its association with parvovirus.