The value of thymus and activation related chemokine immunohistochemistry in classic Hodgkin lymphoma diagnostics.

AIMS: Classic Hodgkin lymphoma (cHL) should be distinguished from its wide variety of histological mimics, including reactive conditions and mature B and T cell neoplasms. Thymus and activation-related chemokine (TARC) is produced in extremely high quantities by the Hodgkin/Reed-Sternberg (HRS) tumour cells and is largely responsible for the attraction of CD4+ T cells into the cHL tumour micro-environment. In the current study we evaluated the diagnostic potential of TARC immunohistochemistry in daily practice in a tertiary referral centre in the Netherlands. METHODS AND RESULTS: A total of 383 cases, approximately half of which were cHL mimics, were prospectively evaluated in the period from June 2014 to November 2020. In 190 cHL cases, 92% were TARC-positive and the majority of cases showed strong and highly specific staining in all HRS cells (77%). In most cases, TARC could discriminate between nodular lymphocyte-predominant and lymphocyte-rich Hodgkin lymphoma. HRS-like cells in mature lymphoid neoplasms were rarely positive (6.4%) and there was no TARC staining at all in 64 reactive lymphadenopathies. CONCLUSIONS: TARC immunohistochemistry has great value in differentiating between cHL and its mimics, including nodular lymphocyte-predominant Hodgkin lymphoma, reactive lymphadenopathies and mature lymphoid neoplasms with HRS-like cells.

The Role of Steroidomics in the Diagnosis of Alzheimer's Disease and Type 2 Diabetes Mellitus.

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17ß-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/ß-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

Combined expression of HOXA11 and CD10 identifies endometriosis versus normal tissue and tumors.

The gold standard for diagnosing endometriosis is by laparoscopic visual demonstration of ectopic endometrial lesions outside the uterus, preferably verified by biopsy and microscopical examination. Molecular markers to facilitate the microscopical diagnosis of endometriosis and for distinguishing endometriosis from other benign and malignant lesions are lacking. Our aim was to test and validate an immunohistochemical antibody panel for improved diagnostic accuracy of endometriosis. Both CD10 and HOXA11 have been implicated in regulation of endometrial homeostasis. Here we have analyzed the expression pattern of these two proteins using immunohistochemistry on human tissues in a tissue microarray format. CD10 and HOXA11 expression in endometriosis lesions were compared to expression patterns in a range of normal tissues and in primary- and metastatic lesions of endometrial-, cervical- and ovarian cancer. HOXA11 and CD10 were expressed in 98% and 91% of endometriosis lesions and the combined double-positive expression profile of both HOXA11 and CD10 was highly sensitive for ectopic endometrial tissue (90%). The specificity and sensitivity for this double-positive signature in endometriosis was significantly different from all investigated tissues, cancers and metastases except normal, eutopic endometrial- and cervical mucosa. The combination of HOXA11 and CD10 expression profiles provides a useful tool to identify ectopic endometrial tissue and for distinguishing endometriosis from various types of gynecological malignancies and metastases.

[From acute coronary syndrome to zoster : Differential diagnostics in segmental and somatic dysfunction of the thoracic spine and ribs]. / Von akutem Koronarsyndrom bis Zoster : Differenzialdiagnostik bei segmentaler und somatischer Dysfunktion an Brustwirbelsäule und Rippen.

BACKGROUND: Segmental and somatic dysfunction in the thoracic section can lead to various clinical symptoms. It is necessary to distinguish three variants. CLINICAL PICTURE: 1. Local pain Potentially life-threatening differential diagnoses have to be considered, and when in doubt chest pain emergency diagnostics must be initiated. 2. Vertebro-visceral reflex The main segmental roots of the sympathetic trunk are in thoracic segments, this results in a high-grade linking to thoracic and abdominal organs. "Non-specific" thoracic and abdominal symptoms can be caused by segmental and somatic dysfunction in thoracic segments. 3. Viscero-vertebral reflex Visceral nociception is transmitted via vegetative fibers to thoracic segments. Here, painful dysfunction can occur, which might be the first sign of severe structural disease like neoplasia or ulcer in thoracic or abdominal organs. DIFFERENTIAL DIAGNOSTICS: Differential diagnostics is challenging, and manual medicine can contribute substantially. Biomechanical and neurophysiologic particularities must be known.

[Complex posttraumatic stress disorder in adults]. / Die Komplexe Posttraumatische Belastungsstörung im Erwachsenenalter.

The term "complex posttraumatic stress disorder" (cPTSD) appeared in the scientific literature 30 years ago and has now been included in a diagnostic catalogue for the first time, namely in the International Statistical Classification of Diseases and Related Health Problems 11 (ICD-11) which was officially published at the beginning of 2022. This usually severely debilitating disorder often poses great challenges to treating physicians and psychotherapists in everyday clinical practice. Due to the much-debated overlap of cPTSD with borderline personality disorder (BPD), which is very high in cases of comorbidity of BPD and PTSD, cPTSD became embroiled in scientific discussions about the raison d'être of BPD in the new dimensional concept of personality disorders (PD) in the ICD-11. In addition to a detailed explanation of the diagnostic criteria of cPTSD and their differentiation from other mental disorders, particularly from PTSD, BPD and dissociative disorders, this article summarizes the historical development of the concept of cPTSD to date and the currently available treatment options. The same criteria apply to cPTSD in childhood and adolescence as in adulthood, but there are some special features that are not addressed in this article.

Ectopic pancreas appearing as a giant gastric cyst mimicking gastric lymphangioma: a case report and a brief review.

BACKGROUND: Ectopic pancreas (EP) is defined as pancreatic tissue that lacks anatomical or vascular communication with the normal body of the pancreas. Despite improvements in diagnostic endoscopy and imaging studies, differentiating ectopic pancreatic tissue from gastric submucosal diseases remains a challenge. CASE PRESENTATION: Here, we present a case of a 44-year-old woman with severe epigastric pain. Initially, gastric lymphangioma was highly suspected due to a well-demarcated protruding mass with a large size that occurred in the submucosal layer of the gastric antrum and appeared as a cystic lesion. The final correct diagnosis of gastric EP was made during surgery. CONCLUSION: Gastric EP with serous oligocystic adenoma appearing as a giant gastric cyst is extremely rare. The difficulty of making an accurate diagnosis and differential diagnosis is highlighted, which may provide additional clinical experience for the diagnosis of EP with serous oligocystic adenoma in the stomach.

Luminescent Analysis of Blood Serum for Diagnostics of Pathological and Pre-Pathological States of Cancer Patients.

This study is devoted to the development of a methodological approach to mathematical analysis and data interpretation of blood serum phosphorescence intensity in cancer patients for determining the pathological states and differential diagnostics of oncological process stages. The purpose of the study is blood serum phosphorescence research in patients with colorectal cancer (CRC) and stomach adenocarcinoma (SAC) and determination of the ultraweak luminescence role for diagnostics of the disease, determining its stages, control of pathogenetic therapy efficiency and forecast of recovery. The values of phosphorescence intensity of blood serum films in patients with CRC and SAC are significantly higher than the corresponding values for the control group. Contrary to the absolute intensity, the relative intensity increase compared to the control group is much more informative for oncoprocess diagnostics, since it exhibits three times increase even at the first stage of tumoral process. Serum phosphorescence intensity continues to increase with progressing of the disease. As the result of our study, the relative intensity increase compared to the first stage can be recommended as an informative indicator for differential diagnostics of oncological process stages. As a conclusion, determination of blood serum phosphorescence intensity can be considered as a sensitive and specific diagnostic method in oncology. With a correct methodological approach to data processing and interpretation, this method can be used in clinical practice for determining the oncopathological states, differential diagnostics of oncoprocess stages and diagnostics of precancer changes, which precede tumoral process development.

DEVIC'S OPTICOMYELITIS: A CASE REPORT FROM THE AUTHORS' CLINICAL PRACTICE.

The aim was to analyze the contemporary scientific literature on Devic's opticomyelitis and to present a case report from our clinical practice. Based on the patient's complaints, case history and features of clinical course, objective neurological status, clinical laboratory and additional examination methods, characteristic MR-patterns, consultations of related specialists and differential diagnostics, we made the clinical diagnosis according to ICD-10: G36.0 Devic's opticomyelitis, exacerbation, with a sustained bilateral lesion of the optic nerves in the form of retrobulbar neuritis with the development of partial atrophy of the optic nerves in both eyes, spinal cord lesions with common cystic, cicatrical and atrophic alterations at C1-Th8 level with moderate lower paraparesis, expressed by sensory ataxia, sensory disturbances by the descending conductive type from Th10, impaired function of pelvic organs by the type of acute urinary retention, asthenic and neurotic syndrome. Widespread cases of demyelinating pathology in medical practice and complexity of differential diagnostics determine the need for a specific diagnostic algorithm. This algorithm should consider anamnestic data along with the course of the disease, clinical, laboratory and instrumental examination, including neuroimaging, analysis of CSF for oligoclonal bands, analysis for IgG antibodies to AQP4, which will allow to carry out diagnostics and to decide on tactics for further management of patients of this cohort. Further research is needed to conduct additional studies for optimization of tactics for dynamics monitoring and improvement of diagnostic, treatment and rehabilitation measures in patients with Devic's opticomyelitis, including appropriate immunological control, given the complexity of differential diagnostics and the affinity of this pathology to multiple sclerosis.

The new differential diagnostic test for the lichenoid drug eruption.

The differential diagnosis between lichenoid drug eruption (LDE) and lichen planus (LP) is difficult due to similar clinical and histological signs but important for treatment and prognosis. The purpose of this study was to propose the new diagnosis method for differentiate LDE from LP. During 2015-2018, 20 patients with confirmed LDE, 13 patients with LP and 134 controls were examined and treated at the Lenoblcenter. All enrolled patients were underwent the injection of 0.5 mL of the 2% lidocaine solution by insulin syringe into the papule with following histological examination. The formation of a blister (bulla) at the site of injection was considered a positive test result. Among LDE, 18 of 20 patients were found positive for developing blister (bulla) and two results were questionable. In 12 of 13 LP patents, bulla on the site of injection was not identified and the result of one patient was nonspecific. All control patients were negative for the proposed test. The histological sections showed that the bulla has corresponded to the separation of the epidermis from the dermis. Intracutaneous injection of 0.5 mL of lidocaine into the papule is an easy highly specific and sensitive method to differentiate LDE from LP.

Morphological features useful in the differential diagnosis between undifferentiated carcinoma and gastrointestinal stromal tumor.

Undifferentiated (sarcomatoid) carcinomas may closely mimic gastrointestinal stromal tumors (GISTs) due to possible histological and immunohistochemical overlap between these two entities. To avoid unnecessary employment of a wide spectrum of immunohistochemical stainings and molecular genetics and thus decrease costs, finding simple morphological features to target further investigation of such neoplasms of the gastrointestinal tract would be helpful. Five cases classified as undifferentiated (sarcomatoid) carcinomas with a definite proof of the diagnosis, i. e. the presence of a differentiated carcinomatous component, were retrieved from archives of several institutions. For comparison, 84 cases of GIST mutated in KIT or PDGFRA genes served as the control group. Hematoxylin and eosin stained slides were evaluated for the presence of patterns which might discriminate between sarcomatoid carcinoma and GIST. Lymphatic invasion and entrapment of fat tissue strongly favor the diagnosis of undifferentiated carcinoma, as it was found in all or almost all cases of undifferentiated carcinoma, but in no GIST. Alternation of low- and high- grade areas, formation of angiosarcomatous-like spaces, and the presence of yolk sac-like areas were also detected in all cases of undifferentiated carcinoma, but only in 1.2%, 2.4% and 7.2% of the GISTs, respectively. Furthermore, DOG1 was negative in all cases of undifferentiated carcinoma. According to this study, the presence of the histological findings listed above should prompt extensive tumor sampling in order to find a differentiated carcinomatous component. However, due to the small number of cases of undifferentiated carcinoma available for the study, a larger multi-institutional study is warranted.

[Fever in systemic lupus erythematosus: disease exacerbation or infection?] / Fieber bei systemischem Lupus erythematodes: Krankheitsschub oder Infektion?

The differential diagnosis of fever, especially in the context of autoimmune diseases is broad. Accordingly, the spectrum of diagnostic procedures is extensive and the therapeutic consequences are partly contradictory. Fever is basically the manifestation of an increased cell proliferation, such as classically seen in tumors, infections or autoimmune inflammation. Systemic lupus erythematosus (SLE) is one of the most multifaceted rheumatological diseases. Fever is one component of the new classification criteria which help to classify and possibly diagnose SLE. The differential work-up of fever is a special challenge for clinicians particularly in the context of the initial diagnosis of SLE or another autoimmune disease and also in the course of the disease in patients with autoimmune diseases. Based on a case report this article discusses differential diagnostic considerations and proposes a concrete differential diagnostic procedure. The patient's history is highlighted as an extremely important source of relevant information. Without claiming completeness various factors are listed, which help to differentiate fever as a consequence of SLE activity versus fever as a consequence of an infection.

[Revised S3 guidelines on schizophrenia : Developmental process and selected recommendations]. / Die aktualisierte S3-Leitlinie Schizophrenie : Entwicklungsprozess und ausgewählte Empfehlungen.

Schizophrenia is one of the most severe mental diseases and leads to significant personal and social impairments for affected persons. The illness is characterized by frequent relapses, results in increased mortality and is associated with the highest socioeconomic costs of all diseases. Moreover, patients with schizophrenia are often stigmatized in everyday life and also in most treatment settings. In 1998 the first German schizophrenia guidelines were published, followed by the first S3 guidelines for schizophrenia in 2006. The revision process started in 2012 coordinated by the German Association for Psychiatry, Psychotherapy and Psychosomatics (DGPPN) and the revised guidelines were published in 2019. The target group for the revised S3 guidelines includes all persons involved in the care of patients with schizophrenia in all sectors of the German healthcare system, including decision makers and insurance funds. Starting with an introduction of the biological, clinical and epidemiological basis of the disorder, recommendations for the diagnostics of schizophrenia, the detection of comorbidities, the use of antipsychotic medication and other somatic procedures, for psychotherapy, psychosocial interventions, handling of special treatment conditions and rehabilitation are made. Finally, recommendations for an evidence-based and optimal coordination within the healthcare system are made, followed by a discussion of the cost-effectiveness of treatment and presentation of strategies for improved quality management. The most important aspect of the revised S3 guidelines on schizophrenia is the multiprofessional cooperation in all phases of the disorder and an empathic and respectful therapeutic alliance.

Immunohistochemistry and molecular genetics in the differential diagnostics of mesenchymal lesions of gastrointestinal tract.

Although, in routine practice, the differential diagnostics of mesenchymal tumors of the gastrointestinal tract is still focused mainly on the correct diagnosis of gastrointestinal stromal tumor and its further therapeutic management based on predictive diagnostics, recent progress in the development of endoscopic techniques has led to increased detection of other mesenchymal lesions, which were previously commonly neglected due to their small size or absence of symptoms requiring surgical exploration. Diagnosis of some of these lesions may be reached based on their histologic pattern alone, while others may be recognized with the use of tissue specific antibodies related to the probable lineage of differentiation of the neoplastic cells. Finally, a subset of tumors, commonly with uncertain lineage of differentiation, is defined by pathognomonic genetic alterations of neoplastic cells. Recognition of such alterations, based either on methods of molecular genetics or immunohistochemical detection of an altered protein product, enables a precise diagnosis in a growing number of these cases. However, regarding the fact that most of these alterations are not unique to a single tumor type, but are often shared by more neoplastic entities, the diagnosis must still be based on a complex diagnostic attitude, reflecting histological, immunohistochemical and molecular genetic features of the investigated tumor.

[Diseases with peripheral motor symptoms]. / Perifériás motoros tünettannal társuló kórképek.

Diseases with peripheral motor symptoms are a rare, but important subgroup of the all peripheral neuropathies, radiculopathies and neuronopathies. In these mostly progressive neuropathies, the clinical features include pure motor symptoms with weakness and wasting of the striated muscles. The differentiation of these diseases is frequently a challenge for qualified clinical neurologists. A careful history taking, the disease time course, the findings of routine clinical physical examination and the electrophysiological studies are all necessary in the diagnostic procedure. The aim of this publication is to overview the clinical characteristics of the pure motor peripheral neuropathies, to consider the diagnostic steps and the differential diagnosis, and finally to summarize the treatment options.

Multiple myeloma: challenges of differential diagnosis (clinical case).

The objective of our study was to interpret and discuss atypical multiple myeloma case. The article describes the case of clinical observation of a patient K, in which manifestations of chronic kidney disease and circulatory failure prevailed in clinical picture of the disease. The authors recommended an X-ray examination of skull and pelvic bones as a screening method suitable for elderly people with symptoms of chronic renal insufficiency and chronic bone and muscle pain resistant to treatment.

[Functional activity of the brain depending on the degree of severity occupational noise-induced hearing loss]. / Funktsional'naya aktivnost' golovnogo mozga v zavisimosti ot stepeni vyrazhennosti professional'noi neirosensornoi tugoukhosti.

Research objective identification of the peculiarities of indicators of audiological examination, registration of somatosensory induced potentials (SSSP), level of constant potential (LCP) and neuropsychological testing in persons of flight composition (LLS) of civil aviation exposed to intra-cabin noise, depending on the degree of expression of professional neurosensory noise (ONIHL). PATIENTS AND METHODS: Thresholds of acoustical sensitivity, levels of perception of shepotny, informal conversation, UPP, characteristic of SSVP, neuropsychological features at 45 patients with easy degree of PNST (LONIHL) and at 50 - with moderate degree of ONIHL (UONIHL) are studied. RESULTS: LCP in the left frontal (Fs), central dark (Pz) leads increased in persons with ONIHL, and the inter-peak interval of the N13-N20 characterizing the central conduct time increased. The FAB, unlike the LONIHL, is characterized by deterioration of cognitive activity in the form of easily pronounced decrease of visual memory functions, expressive speech, FAB scale value indicating priority dysfunction of frontal, dark-occipital lobes, subcortical cerebral structures. CONCLUSION: Neurofunctional markers in UONIHL are the reduction of the indicators of the interfamily relations on the frontal department, conceptual thinking, visual image memory, expressive speech, MMSE and FAB tests, the increase of LCP in the left temporal, central dark, occipital right central N13-N20, inter-peak N25.

[Rheumatoid arthritis-mimics : When appearances are deceptive]. / Rheumatoide Arthritis ­ Mimics : Wenn der Schein trügt.

Rheumatology represents a discipline full of differential diagnoses. Even for classical diseases, such as rheumatoid arthritis as the most frequent chronic inflammatory joint disease and described so clearly in many textbooks, it is not uncommon that it can be a diagnostic challenge in daily practice. This applies to arthritic joint involvement and also to frequently associated extra-articular manifestations. The patient history and results of the clinical examination are essential; however, laboratory and imaging findings often make a significant contribution to confirming the diagnosis, especially in early phases of the disease. This article, which makes no claims to completeness, focuses on diseases that in the opinion of the authors can imitate rheumatoid arthritis due to similar joint and other organ manifestations. These include metabolic, inflammatory infective and non-infective as well as tumorous diseases. A misinterpretation as rheumatoid arthritis as a rule leads to long-term and severe consequences for affected patients. Thus, the diagnosis of rheumatoid arthritis should be questioned and re-evaluated in cases of unusual accompanying symptoms, atypical course of disease and a lack of response to standard treatment approaches.

[Genetics of movement disorders-rare but important]. / Genetik von Bewegungsstörungen ­ selten aber wichtig.

Rare genetic movement disorders are a heterogeneous group of diseases. The causes of many of these rare movement disorders could be resolved due to the progress in molecular genetic diagnostics. This led to a better pathophysiological characterization of rare movement disorders and also to the fact that many phenotypical overlaps could be found between different diseases. The classification of genetic results requires a close cooperation between neurologists and geneticists. Therefore, modern diagnostic procedures cannot replace the clinical classification of genetic movement disorders and the exact patient history. This article provides the reader with an overview of the most important groups of genetic movement disorders. Genetic Parkinson syndromes, dystonia, essential tremor, genetic chorea, cerebellar ataxia and hereditary spastic paraplegia are dealt with in detail. For a better understanding individual genetic terms are explained and differences in molecular genetic diagnostics are presented.

[Early undifferentiated arthritis]. / Frühe undifferenzierte Arthritis.

Early recognition and treatment of inflammatory arthritis is imperative for the further course of the disease. Patients with inflammatory arthritis should be referred as early as possible to a rheumatologist for further management. A combination of anamnesis, clinical examination, imaging and laboratory measurements enable a differential diagnosis. If a specific diagnosis is not possible, the disease is called early undifferentiated arthritis. Early effective treatment should be instituted for those at risk of developing persistent and/or erosive arthritis. Treatment includes both pharmacological and non-pharmacological options. In the management of early arthritis a combination of regular monitoring and optimal treatment interventions are paramount to achieve remission and improve outcome of the disease (treat-to-target).

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 2: clinical features, diagnosis and differential diagnostics.

Gout develops in four stages beginning with an asymptomatic increase in blood levels of uric acid. An acute gout attack is an expression of an underlying inflammatory process, which in the course of time is self-limiting. Without therapy monosodium urate crystals remain in the synovial fluid and synovial membrane and trigger more acute attacks. In the course of the disease monosodium urate crystals form deposits (tophi) leading in severe forms to irreversible joint deformities with loss of functionality. In 20% of cases gout leads to involvement of the kidneys. Overproduction of uric acid can cause nephrolithiasis. These stones can be composed of uric acid or calcium phosphate. Another form of kidney disease caused by gout is uric acid nephropathy. This is a form of abacterial chronic inflammatory response with deposition of sodium urate crystals in the medullary interstitium. Acute obstructive nephropathy is relatively rare and characterized by renal failure due to uric acid precipitation in the tubules because of rapid cell lysis that occurs, for example, with chemotherapy. There is a causal interdependence between the occurrence of hyperuricemia and hypertension. Uric acid activates the renin-angiotensin-aldosterone (RAA) system and inhibits nitric oxide (NO) with the possible consequence of a rise in systemic vascular resistance or arteriolar vasculopathy; however, uric acid is also an apparently independent risk factor for atherosclerosis. In contrast to young patients, the diagnosis of an acute gout attack in the elderly can be a challenge for the physician. Polyarticular manifestations and obscure symptoms can make it difficult to differentiate it from rheumatoid arthritis and calcium pyrophosphate deposition disease (CPPD). Aspiration of synovial fluid with visualization of urate crystals using compensated polarized light microscopy is the gold standard for diagnosis of acute gout. Moreover, analysis of synovial fluid enables a distinction from septic arthritis by Gram staining and bacterial culture. Soft tissue ultrasonography is useful to detect affected synovial tissue and monosodium urate crystals within the synovial fluid. Involvement of bone occurs relatively late in the disease so that x­ray images are not useful in the early stages but might be helpful in differential diagnostics. Dual energy computed tomography (CT) and magnetic resonance imaging (MRI) can be used for certain indications.