Atypical Morphology Research Articles

Verrucous disseminated discoid lupus erythematosus with oral and palmoplantar lesions treated with hydroxychloroquine

Lupus erythematosus (LE) is an autoimmune inflammatory disease with a wide spectrum of cutaneous and systemic manifestations. A unifying concept of this disease is difficult to develop as clinical features of patients with LE show a great variation. Our objective was to present a case of verrucous disseminated discoid lupus erythematosus (DLE) with atypical morphology, extensive involvement, and having oral and palmoplantar lesions. For confirmation of diagnosis, histopathology was done, which showed characteristic findings of DLE. Combination therapy of hydroxychloroquine with oral and topical corticosteroids resulted in resolution of skin lesions. Sometimes, DLE lesions may pose a diagnostic and therapeutic challenge, especially in a case of unusual presentation, as in the given case of hypertrophic LE. These cases require adequate therapy with clinical and histopathological follow-up considering that squamous cell carcinoma may arise in long-standing lesions.

Endodontic management of three rooted premolars with atypical root canal morphology: Case report

Anatomical variations in the root canal morphology is a commonly occurring phenomenon. Arriving at a precise diagnosis clinically and radio-graphically would lead us to appropriate treatment planning which is mandatory for successful outcome of the endodontic treatment. Maxillary and mandibular second premolars have intricate root canal anatomy. The incidence of three rooted premolars is very rare in Indian population, presence of additional roots would make the clinician’s job difficult and challenging. The following case report describes the endodontic and restorative management of maxillary and mandibular second premolar with atypical root canal anatomy being successfully treated with the help of magnification.

A Case of Acute Promyelocytic Leukemia Presenting as Sternal Infiltrate

Granulocytic sarcoma (GS) or myeloid sarcoma (MS) is a localized extramedullary tumor composed of immature myeloid cells which can develop de novo or concurrently with acute myeloid leukemia (AML), myeloproliferative disorders (MPN) or myelodysplastic syndrome (MDS). It can present before, along with or after the diagnosis of acute myeloid leukemia, MPN, MDS or may present as a manifestation of relapse in a previously treated AML patient. The occurrence of MS in an acute promyelocytic leukemia (APL) patient is a very uncommon clinical event especially as initial or primary presentation. APL is often associated with a life threatening coagulopathy making prompt diagnosis and initiation of therapy critical. Unusual clinical localization may lead to misdiagnosis, or delayed diagnosis and treatment. Hence being aware of such atypical presentations of APL is crucial. Here we report a patient with acute promyelocytic leukemia who presented with sternal infiltrate but without any systemic symptoms. The diagnostic challenges are of particular interest given the unusual clinical presentation along with atypical morphology of the abnormal promyelocytes.

Unusual Intracerebral Hemorrhage Secondary to Delayed Posttraumatic Middle Meningeal Artery Pseudoaneurysm, Successfully Treated by Endovascular N-Butyl Cyanoacrylate Embolization

AbstractPseudoaneurysm of the middle meningeal artery, presenting as a delayed sequela of trauma, being a rare entity, may sometimes present as an acute intraparenchymal hemorrhage, with a risk of rerupture and mortality. The optimal management in acute settings remains undetermined. We, hereby, report a case of elderly gentleman with a history of a road traffic accident. Noncontrast computed tomography (NCCT) brain was reported to have left parietal hemorrhagic contusion without any mass effect. The patient was managed conservatively without any major neurological deficits. After 7 months, the patient presented with severe headache, altered sensorium, and right hemiparesis. NCCT brain showed acute left thalamocapsular hemorrhage with minimal subarachnoid hemorrhage with associated mass effect and impending herniation. Considering the fall in patient's baseline Glasgow comma scale response, pupillary asymmetry, and CT findings, immediate decompression and hematoma evacuation were advised. In view of atypical morphology, the patient was planned for urgent digital subtraction angiography prior to the surgery to rule out the ruptured aneurysm or pial arterio-venous fistula. Selective angiography of the left external carotid artery demonstrated a dissecting pseudoaneurysm feeding from the middle meningeal artery (MMA), which was embolized using n-butyl cyanoacrylate (NBCA). Postprocedure DynaCT revealed the left temporal bone fracture, indicating this pseudoaneurysm to be most likely posttraumatic delayed sequelae. Postembolization, the patient underwent surgical decompression and excision of hematoma. Patient's neurological status gradually improved and was discharged with the minimal deficit. Our case highlights the importance of awareness of the posttraumatic MMA pseudoaneurysm as an uncommon but treatable entity, which can be easily diagnosed using cerebral angiography and amenable to safe and effective endovascular embolization using NBCA.

Transcriptome and Proteome of Methicillin-Resistant Staphylococcus aureus Small-Colony Variants Reveal Changed Metabolism and Increased Immune Evasion.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has become a public health crisis. Recently, we isolated small-colony variants (SCVs) of MRSA, which are characterized by slow growth, decreased virulence, increased antibiotic resistance, and immune evasion. In the present study, we provided proteomic and transcriptomic profiles of clinical MRSA sequence type 239 (ST239) normal strains and SCVs and attempted to identify the key genes or pathways closely related to SCV formation and survival. RNAs and proteins were extracted and subjected to RNA sequencing and mass spectrometry, and the transcriptome and proteome were evaluated via bioinformatic analysis. The results were verified by functional assays. In total, 822 differentially expressed genes (DEGs) and 773 differentially expressed proteins (DEPs) were identified; of these, 286 DEGs and DEPs were correlated and subjected to Kyoto Encyclopedia Genes and Genomes analysis. Some pathways were significant, including ABC transporters, ribosome biogenesis, and metabolic pathways such as glycolysis/gluconeogenesis and the citrate cycle (tricarboxylic acid [TCA] cycle). Based on these results, we found that the downregulation of ABC transporters and the TCA cycle pathway resulted in electron transport chain deficiencies and reduced ATP production in SCVs, leading to a dependence on glycolysis and its upregulation. In addition, the upregulation of capsule polysaccharides and the downregulation of surface proteins prevented phagocytosis and reduced the adhesion of host cells, contributing to immune evasion by SCVs. These findings contribute to a better understanding of the mechanisms of SCV formation and survival. IMPORTANCE Small-colony variants (SCVs) of Staphylococcus aureus have drawn increasing research attention. Owing to their slow growth, atypical colony morphology, and unusual metabolic characteristics, SCVs often cause confusion in the laboratory. Furthermore, clinical treatment of SCVs is challenging owing to their antibiotic resistance and immune evasion, leading to persistent and recurrent infections. However, the mechanisms underlying their formation remain unclear. In this study, we isolated SCVs of methicillin-resistant S. aureus and provided transcriptomic and proteomic profiles of normal strains and SCVs. Based on our analysis, glycolysis upregulation and TCA cycle downregulation affected the electron transport chain and energy supply, leading to slower metabolism. Moreover, capsular biosynthesis was increased, while the number of surface proteins decreased, thus promoting immune evasion by SCVs.

Sarcoma of the right femur with heterogeneous morphology similar to myoepithelial carcinoma and amplification of the EWSR1 gene in a 14-year-old boy. Clinical observation and literature review

Ewing sarcoma (ES) is one of the most frequent primary bone tumors and has a well-studied diagnostically important genetic background. However, there are primary bone round-cell tumors with atypical morphology different from conventional ES, tumors with rearrangement of the EWSR1 gene with partner genes not from the ETS gene family, tumors with unusual changes in the EWSR1 gene (amplification or deletion), which can cause significant diagnostic difficulties. In this article, we will describe a case of a primary bone tumor with an atypical morphology similar to myoepithelial carcinoma, where an amplification of the EWSR1 gene was detected. According to morphological, immunological, genetic and clinical signs, this tumor was classified as a sarcoma from the EWSR1::non-ETS group of round-cell sarcomas, namely a sarcoma with EWSR1::NFATC2 rearrangement, first formalized in the WHO classification of soft tissue tumors in 2020.

Evidence for upregulation of excitatory synaptic transmission in the substantia nigra in Schizophrenia: a postmortem ultrastructural study.

The dopamine hypothesis of schizophrenia suggests that psychotic symptoms originate from dysregulation of dopaminergic activity, which may be controlled by upstream innervation. We hypothesized that we would find anatomical evidence for the hyperexcitability seen in the SN. We examined and quantified synaptic morphology, which correlates with function, in the postmortem substantia nigra (SN) from 15 schizophrenia and 12 normal subjects. Synapses were counted using stereological techniques and classified based on the morphology of the post-synaptic density (PSD) and the presence or absence of a presynaptic density. The density and proportion of excitatory synapses was higher in the schizophrenia group than in controls, while the proportion (but not density) of inhibitory synapses was lower. We also detected in the schizophrenia group an increase in density of synapses with a PSD of intermediate thickness, which may represent excitatory synapses. The density of synapses with presynaptic densities was similar in both groups. The density of synapses with mixed morphologies was higher in the schizophrenia group than in controls. The human SN contains atypical synaptic morphology. We found an excess amount and proportion of excitatory synapses in the SN in schizophrenia that could result in hyperactivity and drive the psychotic symptoms of schizophrenia. The sources of afferent excitatory inputs to the SN arise from the subthalamic nucleus, the pedunculopontine nucleus, and the ventral tegmental area (VTA), areas that could be the source of excess excitation. Synapses with mixed morphologies may represent inputs from the VTA, which release multiple transmitters.

Transformation of recurrent ALK-positive anaplastic large-cell lymphoma from common pattern to composite pattern (lymphohistiocytic and small-cell pattern) with a change in CD30 expression.

ALK-positive anaplastic large-cell lymphoma (ALK + ALCL) is characterized by expression of ALK and CD30. The current World Health Organization (WHO) classification recognizes five morphologic patterns: common, small-cell, lymphohistiocytic, Hodgkin-like, and composite. There are few reports about the morphologic transformation of ALK + ALCL. Today, we report an intriguing case of presumed transformation from common-pattern to composite-pattern (lymphohistiocytic and small-cell pattern) ALK + ALCL, with CD30 expression changing from positive to negative. This case expands understanding of morphologic transformation between different subtypes of ALK + ALCL and highlights common diagnostic pitfalls, including atypical morphology and negative CD30. Morphologic transformation of ALK + ALCL should be assigned importance, and comprehensive clinical history, histologic and immunophenotypic evaluation are vital to rendering the correct diagnosis of ALK + ALCL.

Acanthosis Nigricans: An Updated Review.

Early recognition of acanthosis nigricans is important because acanthosis nigricans can be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy. The purpose of this article is to familiarize pediatricians with the clinical manifestations, evaluation, diagnosis, and management of acanthosis nigricans. A search was conducted in November 2021in PubMed Clinical Queries using the key term "acanthosis nigricans". The search strategy included all clinical trials, observational studies, and reviews published within the past 10 years. Only papers published in the English literature were included in this review. The information retrieved from the above search was used in the compilation of the present article. Acanthosis nigricans is characterized by symmetric, hyperpigmented, and velvety plaques with ill-defined borders, typically involving intertriginous areas. Obesity is the most common cause of acanthosis nigricans which is increasingly observed in obese children and adolescents and can serve as a cutaneous marker of insulin resistance. Early recognition of acanthosis nigricans is important because acanthosis nigricans can also be a cutaneous manifestation of a variety of systemic disorders and, rarely, as a sign of internal malignancy. This may consist of weight reduction, discontinuation of causative drugs, treatment of underlying endocrinopathy, or treatment of an underlying malignancy. For patients with isolated acanthosis nigricans and for those whose underlying cause is not amenable to treatment, treatment of the lesion may be considered for cosmetic reasons. Topical retinoids, vitamin D analogs, chemical peels, and other keratolytics are often used for the treatment of localized lesions. Seldom, systemic therapy such as oral retinoids may be considered for extensive or generalized acanthosis nigricans and acanthosis nigricans unresponsive to topical therapy. Other uncommon treatment modalities include dermabrasion, laser therapy, and surgical removal. Although acanthosis nigricans is treatable, a complete cure is difficult to achieve. The underlying cause should be treated, if possible, to resolve and prevent the recurrence of acanthosis nigricans. The diagnosis is mainly clinical, based on the characteristic appearance (symmetrically distributed, hyperpigmented, velvety, papillomatous, hyperkeratotic plaques with ill-defined borders) and the typical sites (intertriginous areas, flexural area, and skin folds) of the lesions. The diagnosis might be difficult for lesions that have atypical morphology or are in an unusual location. Clinicians should be familiar with the clinical signs, evaluation, diagnosis, and therapy of acanthosis nigricans because of the link between it and underlying diseases.

Genetic and epigenetic analysis of hepatocellular adenomas with atypical morphological features.

Hepatocellular adenoma (HCA) is a rare liver tumour, which can have atypical morphological features such as cytological atypia, pseudoglandular architecture, and altered reticulin framework. Little is known about the genetic and epigenetic alterations of such HCAs and whether they show the alterations classically found in hepatocellular carcinoma (HCC) or in HCA without atypical morphology. We analysed five HCAs with atypical morphological features and one HCA with transition to HCC. Every tumour was subtyped by immunohistochemistry, sequenced by a targeted NGS panel, and analysed on a DNA methylation microarray. Subtyping of the five HCAs with atypical features revealed two β-catenin mutated HCA (b-HCA), two β-catenin mutated inflammatory HCA (b-IHCA), and one sonic hedgehog activated HCA (shHCA). None of them showed mutations typically found in HCC, such as, e.g. TERT or TP53 mutations. The epigenomic pattern of HCAs with atypical morphological features clustered with reference data for HCAs without atypical morphological features but not with HCC. Similarly, phyloepigenetic trees using the DNA methylation data reproducibly showed that HCAs with morphological atypia are much more similar to nonmalignant samples than to malignant samples. Finally, atypical HCAs showed no relevant copy number variations (CNV). In our series, mutational, DNA methylation, as well as CNV analyses, supported a relationship of atypical HCAs with nonatypical HCAs rather than with HCC. Therefore, in cases with difficult differential diagnosis between HCC and HCA, it might be advisable to perform targeted sequencing and/or combined methylation/copy number profiling.

Papillomatous breast lesions with atypical columnar cell features

AimsColumnar cell lesions (CCLs) are recognised breast cancer precursor lesions. Intraductal papillomas are usually lined by benign (polyclonal) cells. Although papillomas with monoclonal lesions (atypical ductal hyperplasia (ADH)/ductal carcinoma in...

Large B-cell lymphoma with IRF4 gene rearrangements: Differences in clinicopathologic, immunophenotypic and cytogenetic features between pediatric and adult patients

Large B-cell lymphoma (LBL) with interferon regulatory factor 4 (IRF4) rearrangement (LBL-IRF4), a provisional entity in the 2017 WHO classification, primarily arises in children and young adults and has a favorable prognosis. However, few studies have addressed the clinicopathologic and cytogenetic features of older adults with IRF4-rearranged B-cell lymphomas. From a database of all internal and external cases (08/01/2015 to 12/01/2020) on which interphase fluorescence in situ hybridization was performed at the Mayo Clinic, we identified 43 patients with B-cell lymphoma and IRF4 rearrangements. Consistent features included large cell morphology, expression of CD20, BCL6, and MUM1, and absence of MYC-R. All pediatric cases (n=12) arose in Waldeyer's ring (WR), cervical lymph node (CLN), or bowel, and lacked BCL6-R and BCL2-R, and all but one showed classic morphology. Adults with WR, CLN, or bowel involvement (n=22) were younger (median 32 years). Their lymphomas resembled pediatric cases morphologically and lacked BCL2-R, although 30% harbored BCL6-R (P=0.043). Lymphomas that involved other anatomic sites (n=9) arose in older adults (median 68 years; P=0.002) and often showed atypical morphology (P<0.001). All lacked BCL6-R and 2 of 4 harbored BCL2-R (P<0.001). LBL-IRF4 - arising in WR, CLN, or bowel may represent a distinct clinicopathologic entity characterized by pediatric/younger adult age, classic morphology, and lack of BCL2-R. In contrast, B-cell lymphomas with IRF4-R that arise in other sites usually involve older adults, are often morphologically atypical and/or harbor BCL2-R, and may be more akin to diffuse LBL, not otherwise specified.

The spectrum of intestinal mature T- and NK-cell neoplasms in a tertiary center in Taiwan with a high frequency of perforation.

Primary intestinal T-cell lymphomas (PITLs) comprise enteropathy-associated T-cell lymphoma (EATL), monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), extranodal NK/T-cell lymphoma (ENKTL), anaplastic large cell lymphoma (ALCL), and intestinal T cell lymphoma, NOS (ITCL-NOS). MEITL is composed of monomorphic medium cells expressing CD8 and CD56, with a cytotoxic phenotype. We retrospectively analyzed 77 cases of intestinal T-cell lymphomas, 71 primary and six secondary, at a tertiary center in Taiwan from 2001 to 2021. Perforation occurred in 57 (74%) patients, including 56 (73%) at presentation and one after chemotherapy. The primary cases included MEITL (68%), ENKTL (14%), ITCL-NOS (13%), ALCL (4%), and EATL (1%). The perforation rate was 90%, 70%, and 22% in MEITL, ENKTL, and ITCL-NOS cases, respectively (p<0.0001, Fisher's exact test). Most (75%; n=36) MEITL cases were typical; while seven (15%) had atypical morphology and five (10%) exhibited atypical immunophenotype. The tumor cells of ITCL-NOS were pleomorphic, with various expression of CD8 or CD56. All METIL, ITCL-NOS and ALCL cases were negative for EBER; while all ENKTL cases, either primary or secondary, were positive for cytotoxic granules and EBER. The prognosis of PITL was poor, with a medium survival of 7.0, 3.3, and 3.7 months among patients with MEITL, ENKTL, and ITCL-NOS, respectively. Of the six secondary cases, the primary tumors orginated from nasal ENKTL (n=5) and cutaneous PTCL-NOS (n=1). We showed a wide spectrum of intestinal T-cell lymphomas in Taiwan, with MEITL as the most common PITL, a high rate of perforation, and a wider morphological and immunophenotypic spectrum.

HIV-1 infected humanized DRAGA mice develop HIV-specific antibodies despite lack of canonical germinal centers in secondary lymphoid tissues.

A major barrier in the use of humanized mice as models of HIV-1 (HIV) infection is the inadequate generation of virus-specific antibody responses. Humanized DRAGA (hDRAGA) mice generate antigen-specific class switched antibodies to several pathogens, but whether they do so in HIV infection and the extent to which their secondary lymphoid tissues (sLT) support germinal center responses is unknown. hDRAGA mice were evaluated for their ability to support HIV replication, generate virus-specific antibody responses, develop splenocyte subsets, and organize sLT architecture. hDRAGA mice supported persistent HIV replication and developed modest levels of gp41-specific human IgM and IgG. Spleens from uninfected and HIV infected hDRAGA mice contained differentiated B and CD4+ T cell subsets including germinal center (GC) B cells and T follicular helper cells (TFH); relative expansions of TFH and CD8+ T cells, but not GC B cells, occurred in HIV-infected hDRAGA mice compared to uninfected animals. Immunofluorescent staining of spleen and mesenteric lymph node sections demonstrated atypical morphology. Most CD4+ and CD8+ T cells resided within CD20hi areas. CD20hi areas lacked canonical germinal centers, as defined by staining for IgD-Ki67+cells. No human follicular dendritic cells (FDC) were detected. Mouse FDC were distributed broadly throughout both CD20hi and CD20lo regions of sLT. HIV RNA particles were detected by in situ hybridization within CD20+ areas and some co-localized with mouse FDC. Viral RNA+ cells were more concentrated within CD20hi compared to CD20lo areas of sLT, but differences were diminished in spleen and eliminated in mesenteric lymph nodes when adjusted for CD4+ cell frequency. Thus, hDRAGA mice recapitulated multiple aspects of HIV pathogenesis including HIV replication, relative expansions in TFH and CD8+ T cells, and modest HIV-specific antibody production. Nevertheless, classical germinal center morphology in sLT was not observed, which may account for the inefficient expansion of GC B cells and generation of low titer human antibody responses to HIV-1 in this model.

Natural history and ecological effects on the establishment and fate of Florida carpenter ant cadavers infected by the parasitic manipulator Ophiocordyceps camponoti‐floridani

Abstract Ophiocordyceps fungi manipulate the behaviour of their ant hosts to produce a summit disease phenotype, thereby establishing infected ant cadavers onto vegetation at elevated positions suitable for fungal growth and transmission. Multiple environmental and ecological factors have been proposed to shape the timing, positioning and outcome of these manipulations. We conducted a long‐term field study of Ophiocordyceps camponoti‐floridani infections of Camponotus floridanus ants—the Florida zombie ants. We propose and refine hypotheses on the factors that shape infection outcomes by tracking the occurrence of and fungal growth from hundreds of ant cadavers. We modelled and report these data in relation to weather, light, vegetation and attack by hyperparasites. We investigated environmental factors that could affect the occurrence and location of newly manipulated ant cadavers. New cadaver occurrence was preferentially biased towards epiphytic Tillandsia bromeliads, canopy openness and summer weather conditions (an interactive effect of temperature, humidity and precipitation). Furthermore, we suggest that incident light at the individual cadaver level reflects microhabitat choice by manipulated ants or selective pressure on cadaver maintenance for conditions that improve fungal survival. We also asked which environmental conditions affect fungal fitness. Continued fungal development of reproductive structures and putative transmission increased with moist weather conditions (interaction of humidity and precipitation) and canopy openness, while being reduced by hyperparasitic mycoparasite infections. Moreover, under the most open canopy conditions, we found an atypical Ophiocordyceps growth morphology that could represent a plastic response to conditions influenced by high light levels. Taken together, we explore general trends and the effects of various ecological conditions on host and parasite disease outcomes in the Florida zombie ant system. These insights from the field can be used to inform experimental laboratory setups that directly test the effects of biotic and abiotic factors on fungus–ant interactions or aim to uncover underlying molecular mechanisms. Read the free Plain Language Summary for this article on the Journal blog.

Atypical Megakaryocyte Morphology: an Important Diagnostic Clue for JAK2 Mutation–Associated Disorders

Atypical Megakaryocyte Morphology: an Important Diagnostic Clue for JAK2 Mutation–Associated Disorders

Gunshots through laminated glass: expelled compounded fragments as a function of bullet type

In the frame of an experimental setting, the formation of round-shaped compounded glass fragments on the exit site after gunshots through a windshield was examined. For that purpose, a 9 × 19 mm pistol (HK P30) and two different cartridges containing (a) a full metal jacketed round-nosed projectile and (b) a deformation projectile were used. On the basis of 52 gunshots, the morphology, impact angles and terminal ballistics of occurring compounded glass fragments were examined. The results showed that the compounded glass fragments’ morphology allowed for the differentiation of two used projectiles. Fragments were able to cause round-shaped defects in a single cotton layer (T-shirt) with subsequent penetration of up to 2.4 cm into ballistic gelatin (10%, 4 °C). As a function of the projectile type, the compounded glass fragments showed different reproducible impact angles that differed notably from the known conical pattern of expelled glass fragments after bullet penetration. These findings might help to explain the atypical morphology of gunshot wounds with laminated glass as an intermediate target and prevent possible misinterpretations when reconstructing the sequence of events.

Anatomical study of circle of Willis on fresh autopsied brains. A study of a Romanian population.

Because the circle of Willis (CoW) supplies blood to the brain in case of occlusion of one of the cerebral arteries, identification of any change in its classical shape could be useful in the assessment of cerebrovascular morbidity. The purpose of our research was to study the anatomical variants of CoW identified on fresh brains obtained at the clinical autopsies of adult deceased patients belonging to a specific population (Northeastern region of Romania), as no data are available for Romania population up to date. The study group included consecutive patients who died in Prof. Dr. Nicolae Oblu Emergency Clinical Hospital, Iaşi, Romania, due to medical causes between January 1, 2014 and June 30, 2016, to whom a clinical autopsy was performed. From a total of 96 circles of Willis, 29.17% presented an atypical morphology. We identified eight types of anatomical variants, which affected simultaneously both the posterior and the anterior parts of CoW in 46.42% of cases. The most frequent anatomical variants were hypoplasia (20.91%), followed by the absence of an artery (3.06%), and partially fetal type artery (2.04%). 67.86% of atypical CoW exhibited more than one anatomical variant of an artery in one circle. We identified nine of the 23 morphological patterns that were published to date, and also nine new types. Our research proved that in the population living in the Northeastern part of Romania the anatomical variations of circles of Willis are very polymorphic, with particular morphological aspects.

Evolution in the definition and diagnosis of the Hodgkin lymphomas and related entities.

Hodgkin lymphoma was the first of the lymphomas to be recognized as a specific disease entity. However, recent studies have highlighted the heterogeneity of the diseases associated with this eponym warranting clarification and refinement of diagnostic terminology. While classic Hodgkin lymphoma (CHL) remains an essentially unchanged diagnostic entity in the 2022 International Consensus Classification of Mature Lymphoid Neoplasms (2022 ICC), nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is now renamed nodular lymphocyte predominant B cell lymphoma (NLPBL) in recognition of the distinct pathologic, biologic, and clinical differences. Fan patterns A, B, and C (sharing the presence of evident follicular structures, and retention of a B cell rich background) will be combined in "typical" or grade 1, while the other "variant" patterns, D, E, and F, are considered grade 2. T-cell/histiocyte-rich large B cell lymphoma (THRBCL) is considered part of the "variant" NLPHL continuum.The entity previously known as "B cell lymphoma, unclassifiable (BCLU), with features intermediate between diffuse large B cell lymphoma (DLBCL) and CHL" has been renamed "mediastinal gray zone lymphoma" (MGZL) in recognition of the importance of the thymic niche in the biology of this tumor. The diagnostic criteria for MGZL have been refined and require both a high tumor cell density and a strongly preserved B cell program.This article will describe updates on CHL, NLPBL, and MGZL in the recently published 2022 ICC and provide some useful differential diagnostic clues in cases with atypical morphology or immunophenotype.

A Peculiar Wide Complex Tachycardia During Flecainide Treatment.

A Peculiar Wide Complex Tachycardia During Flecainide Treatment.