Distinct Histopathological Entity Research Articles

Preoperative and postoperative memory in epilepsy patients with ‘gliosis only’ versus hippocampal sclerosis: a matched case–control study

BackgroundGliosis only (GO) and hippocampal sclerosis (HS) are distinct histopathological entities in mesial temporal lobe epilepsy. This study explores whether this distinction also exists on a functional level when evaluating...

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE): a widespread disease with an apparently focal epilepsy.

Mild malformation of cortical development with oligodendroglial hyperplasia and epilepsy (MOGHE) is a recently recognized, highly epileptogenic, distinct histopathological entity in drug-resistant epilepsy that primarily involves the frontal lobes. Surgical outcomes in MOGHE are variable. Although the diagnosis is based on histopathology, high-resolution MRI helps to differentiate MOGHE preoperatively from other forms of cortical malformations (i.e., mMCD II and FCD IIa). We discuss the clinical, electrographic, radiological and histopathological characteristics of MOGHE in two patients who underwent evaluation for drug-resistant epilepsy followed by electrocorticography-based resection. Both patients presented with childhood-onset refractory frontal lobe epilepsy with a high seizure burden. Interictal epileptiform discharges were widespread. PET abnormalities were disproportionate to the MRI findings. Cognitive impairment, persistent epileptiform discharges on post-resection electrocorticography and sub-optimal surgical outcomes suggest that MOGHE is a widespread pathology in focal epilepsy.

Imaging of Breast Cancers With Predilection for Nonmass Pattern of Growth: Invasive Lobular Carcinoma and DCIS-Does Imaging Capture It All?

OBJECTIVE. Invasive lobular carcinoma (ILC) and ductal carcinoma in situ (DCIS) are distinct histopathologic entities with several commonalities: both have subtle clinical and imaging presentation, have been linked with controversy regarding optimal imaging techniques and management, and exemplify the codependence of adequate imaging evaluation and optimal treatment strategies in breast care. CONCLUSION. We review molecular mechanisms and histopathologic patterns that define the biologic behavior of both ILC and DCIS and discuss how these mechanisms translate into distinct clinical and imaging presentations that affect the staging workup and patient management algorithm.

Focal aggregates of normal or near normal uveal melanocytes (FANNUMs) in the choroid: a distinct clinical and histopathological entity?

PurposeTo define, describe, and illustrate a previously unreported category of discrete melanotic choroidal melanocytic lesion.MethodsProspective ophthalmoscopic study of the ocular fundi of 79 light-skinned persons 50 years of age or older not referred for any evident fundus lesion, with detection of all evident discrete melanotic choroidal lesions > 0.3 mm in largest basal diameter.ResultsOne or more discrete dark-brown to gray choroidal lesions > 0.3 mm in largest basal diameter were detected in 27 of the 79 evaluated subjects (34.2%). All but four of the detected lesions were “flat” by both ophthalmoscopy and ultrasonography. A single flat lesion was present in one eye of 14 subjects whose fellow eye was normal, 2 or more flat lesions were evident in one eye of 5 subjects whose other eye was normal, and one or more lesions were evident in both eyes of 6 subjects.ConclusionWhile some of the discrete small, flat melanocytic choroidal lesions detected in this study might have been choroidal nevi, the author hypothesizes that an indeterminate proportion of them may have been focal aggregates of normal or near normal uveal melanocytes (FANNUMs).

Sinonasal cancer: an overview of the emerging subtypes.

Advances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised. This review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies. Although rare, knowledge of sinonasal neoplasm subtypes has implications for prognosis, treatment strategies and the development of novel therapeutic targets.

Primary Pulmonary Tumors in Pediatric Population: Imaging Markers for Predicting Histology.

Objectives:The objective of the study was to review the imaging features of proven pediatric primary lung tumors, with a purpose of detecting key distinguishing features among the various entities.Materials and Methods:We retrospectively reviewed multidetector computed tomography (CT) images of 17 pediatric patients with primary lung tumors. For each examination, various CT image descriptors were used to characterize the pulmonary nodules/masses; including location, size, number, morphology, cavitation, calcification, intense enhancement, airway involvement, chest wall/pleural involvement, mediastinal/vascular involvement, and nodal enlargement.Results:The age of the patients ranged from 2 to 18 years (mean age of 9.5 years). Approximately 35.3% of tumors were benign and 64.7% were aggressive/malignant. Nine distinct histopathologic tumor entities were found. Common tumor types were recurrent respiratory papillomatosis (4) and inflammatory myofibroblastic tumor (4) with two endobronchial tumors including carcinoid and mucoepidermoid carcinomas. Besides invasion and nodal enlargement, large size and central location (P < 0.05) were predictors of aggressiveness/malignancy. Multiple lesions and cavitation (P < 0.05), on the other hand, were frequent in benign lesions.Conclusion:On imaging, location and morphological markers can allow diagnosis in majority of the tumors.

Multinucleate cell angiohistiocytoma: A clinicopathologic study of 62 cases and proposed diagnostic criteria.

Multinucleate cell angiohistiocytoma (MCAH) is an uncommon and likely underdiagnosed entity that is thought to be of vascular and fibrohistiocytic origin. We retrospectively reviewed all cases diagnosed as MCAH at the Yale Medicine Dermatopathology laboratory between 1 January 1990 and 1 September 2018. Sixty-two cases were retained. We performed immunohistochemistry on the ten most inflamed lesions found and assessed for a possible alteration within the Wnt/ß-catenin signaling pathway, involved in follicular induction in dermatofibroma. We subsequently established histologic diagnostic criteria to differentiate MCAH from its mimickers. MCAH affected both genders equally. The hands or fingers were affected in 51.6% of cases. We found the most specific histologic criteria to be: (a) presence of odd multinucleated fibroblasts, (b) presence of superficial parallel fibrosis, (c) presence and thickening of superficial papillary dermal vessels, and (d) absence of perifollicular fibrosis. As for immunoreactivity, we found positivity to CD138, CD163, and CD117 in the mononuclear inflammatory infiltrate. There was no histopathologic evidence of follicular induction, as can be seen in dermatofibromas, and no expression of nuclear beta-catenin as seen in dermatofibromas with follicular induction. This large case series establishes MCAH as a distinct clinical and histopathologic entity.

WNK Bodies Develop in the Distal Convoluted Tubule of the Human Kidney in Chronic Hypokalemia

Hypokalemia contributes to the progression of chronic kidney disease and is associated with the distinct histopathological entity of chronic hypokalemic nephropathy. K+ deficiency results in profound alterations of renal epithelial transport. These include an increase of salt reabsorption via the Na+, Cl−-cotransporter (NCC) of the distal convoluted tubule (DCT), which minimizes K+ wasting in downstream nephron segments. Within days to hours of dietary K+ depletion, punctate structures in the DCT containing crucial NCC-regulating kinases arise in the murine DCT. In the recent literature, these structures have been termed “WNK bodies”, referring to their essential components, with no lysine (WNK) kinases. We hypothesized that hypokalemia may stimulate WNK body formation in humans. Renal needle biopsies of patients with chronic hypokalemic nephropathy (n=2) and appropriate controls were examined by electron microscopy, histological stains and immunofluorescence. Staining of segment- and organelle-specific marker proteins were used to characterize the intrarenal and subcellular distribution of established WNK body constituents, namely WNK and Ste20-related proline-alanine-rich (SPAK) kinases. In hypokalemic patients, WNKs and SPAK concentrated in non-membrane bound cytoplasmic regions in the DCT, consistent with prior descriptions of WNK bodies. The putative WNK bodies were located in the perinuclear region and were closely adjacent to microtubules, but not clustered in aggresomes. Notably, we provide the first report of WNK bodies, which are functionally challenging structures associated with K+ deficiency, in human patients. Support or Funding Information Deutsche Forschungsgemeinschaft (MU 2924/2-1,2 und BA 700/22-1,2; INST 335/596-1 FUGG) Immunofluorescent staining of SPAK and pS-WNK SPAK and catalytically active WNK isoforms are colocalized in punctate accumulations in the DCT of hypokalemic patients (top); these are absent in controls (bottom). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cystic neutrophilic granulomatous mastitis: A clinicopathologic study of a distinct entity with supporting evidence of a role for Corynebacterium-targeted therapy

Cystic neutrophilic granulomatous mastitis (CNGM) is a distinct histopathologic entity characterized by neutrophilic and granulomatous inflammation surrounding clear cystic spaces. Rare gram-positive bacilli are sometimes identified within these cystic spaces. Studies in the literature have identified these gram-positive bacilli to be Corynebacterium species. We describe the clinicopathologic features of 7 cases of CNGM, including a case with evidence of Corynebacterium amycolatum. Patients were young to middle aged parous women ranging in age from 28 to 53 years (median age: 41 years). Gram-positive bacilli were identified in 4 cases, all within cystic spaces. Microbial culture from a 41-year old Hispanic woman grew Corynebacterium species on multiple occasions and Corynebacterium amycolatum was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) on two separate occasions. Antibiotic susceptibility testing performed both times showed resistance to multiple antibiotics and susceptibility to vancomycin. Follow-up of all patients (range 3–12 months, median 6 months) showed a widely variable clinical course and varying response to a variety of treatment modalities. Five of the seven CNGM patients were parous, reproductive-aged Hispanic women who were born outside of the United States. Our findings further support the association of CNGM with corynebacteria and gram-positive bacilli. Furthermore, this study shows that Corynebacterium amycolatum, a nonlipophilic and multidrug-resistant corynebacterium can be associated with CNGM, hence the need for targeted antibiotic therapy. We propose identifying corynebacteria to the species level and performing antibiotic susceptibility testing in patients with CNGM because of the varied susceptibility testing profile that has been reported among different species of corynebacteria.

Sclerosing Angiomatoid Nodular Transformation of the spleen in a four-year-old with anemia

Abstract Sclerosing Angiomatoid Nodular Transformation (SANT) of the spleen, first reported as a distinct histopathological entity in 2004, is exceedingly rare in children. The clinical progression and pathophysiologic features of this disease are poorly described in the literature. We performed a literature review of reported cases of SANT. Out of 258 reported cases, only five were in children. We present a sixth case of SANT in a four-year-old boy who presented with chronic anemia and elevated inflammatory markers. The relative variability in case presentation and the clinical concern for malignancy, warrant further disease characterization and discussion of management.

Cystic Biliary Atresia and Choledochal Cysts Are Distinct Histopathologic Entities.

Cystic biliary atresia (CBA), a rare cystic expansion of atretic extrahepatic bile ducts in young infants, overlaps in age at presentation and imaging features with early choledochal cysts (CC). Treatment and prognosis differ; histologic differences are unsettled. We compared 10 patients with CBA, 1975 to 2015, to an age-similar cohort of 13 infants, and to older patients who had surgery for CC. Operative details, imaging, and clinical courses were correlated to pathologic specimens. Immunostains for smooth muscle actin and myosin heavy chain were used to evaluate cyst walls and atretic segments. CBA cysts typically lacked epithelium and inflammation; cyst walls had an inner, dense cicatricial layer associated with myofibroblastic (MF) hyperplasia that often delaminated producing a grossly visible inner cyst wall. Seven proximal biliary remnants in CBA featured circumferential peribiliary MF hyperplasia/fibrosis with little or no inflammation, similar to isolated BA. Extrahepatic atresia was usually both proximal and distal to the cyst. Features in 10/13 CC from infants and 8/8 CC in older patients had mostly preserved uninjured epithelium and no subepithelial cicatrix. Mural smooth muscle (absent in CBA) was present to some extent in CC at all ages. Unexpectedly, focal MF hyperplasia and laminar sclerosis was present in a few CC in infants, resembling CBA. CBA and infant CC are distinct histologic entities that occasionally overlap. CBA bile duct injury mimics non-CBA. Cystification is an aberrant manifestation of stromal proliferation in BA. The current management approach assuming CBA and CC in infants are 2 separate disease processes is supported but caution is advised.

Heterotopic pancreatic rests: imaging features, complications, and unifying concepts

The spectrum of pancreatic heterotopia will be reviewed, including clinical features, potential complications, and imaging manifestations. This will also include a review of various entities associated with pancreatic heterotopia such as groove pancreatitis and cystic dystrophy of gastroduodenal heterotopic pancreas. These entities were previously thought of as distinct histopathologic entities but now appear to represent manifestations of pancreatic heterotopia. Pancreatic heterotopia and heterotopic pancreatitis can have a wide range of appearances. Several entities, which were previously thought to be distinct, can be considered manifestations of pancreatic heterotopia and heterotopic pancreatitis.

MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer.

Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion. Reversely, inhibition of miR-373 allowed mesenchymal IEC to regain epithelial properties, which correlated with absence of neoplastic progression. Using xenografts in mice demonstrated miR-373-mediated acceleration of malignant intestinal tumor growth. In conclusion, our results provide first evidence that miR-205 and miR-373 may differentially contribute to the aggressive phenotype of MAC in CRC.

SEPN1-related myopathy in three patients: novel mutations and diagnostic clues

Mutations in SEPN1 cause selenoprotein N (SEPN)-related myopathy (SEPN-RM) characterized by early-onset axial and neck weakness, spinal rigidity, respiratory failure and histopathological features, ranging from mild dystrophic signs to a congenital myopathy pattern with myofibrillar disorganization. We report on clinical and instrumental features in three patients affected with a congenital myopathy characterized by prevalent neck weakness starting at different ages and mild myopathy, in whom we performed diagnosis of SEPN-RM. The patients presented myopathic signs since their first years of life, but the disease remained unrecognized because of a relatively benign myopathic course. In two cases, myopathic features were stable after 2years of follow-up, but respiratory involvement worsened. The muscle MRI and muscle biopsy showed a typical pattern of SEPN-RM. Molecular diagnosis revealed two novel homozygous mutations in SEPN1, c.1176delA and c.726_727InsTCC. This report underlines the clinical diagnostic clues of early neck and axial weakness to suspect a SEPN-RM and the usefulness of muscle MRI in conjunction with clinical features to achieve the diagnosis. Our data confirm the slow progression of respiratory involvement in spite of the relatively stable course of myopathy. We report two previously undescribed mutations in SEPN1. • Mutations in SEPN1 cause myopathy characterized by early-onset axial and neck weakness spinal rigidity and respiratory failure. • SEPN-related myopathies have been initially associated with four distinct histopathological entities that however appear more mixed in recently described cases. What is New: • SEPN-related myopathies can remain unrecognized because of the normal early motor development and relatively benign myopathic course of the disease. • Our study adds two novel homozygous mutations to the number of reported pathogenic SEPN1 variants.

Localized overexpression of alpha-internexin within nodules in multinodular and vacuolating neuronal tumors

Multinodular and vacuolating neuronal tumors (MVNT) have been recently referred to as a distinctive neuronal tumor entity based on histopathological findings. They are characterized by multiple tumor nodules, vacuolar alteration and widespread immunolabeling for human neuronal protein HuC/HuD. Only 13 cases have been reported in the literature to date and little is known about the histopathology of these tumors. Herein, we report a case of MVNT with additional confirmation of immunohistochemical features. A 22-year-old woman presented with a continuous headache. MRI showed a subcortical white matter lesion with multiple satellite nodules in the frontal lobe appearing as T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities. Histological examination of the resected lesion revealed well-defined multiple nodules composed of predominant vacuolating tumor cells. The tumor cells exhibited consistent immunolabeling for doublecortin, as well as HuC/HuD, both representative neuronal biomarkers associated with earlier stages of neuronal development. Immunopositivity for oligodendrocyte transcription factor 2 (Olig2) and S100 was also detected in tumor cells. Additionally, significant overexpression of alpha-internexin was observed in the background neuropil limited to tumor nodules. Neuronal nuclear antigen (NeuN), synaptophysin and neurofilament, markers for mature neurons, were either negative or weakly positive. The expression profile of neuronal biomarkers can be distinguished from that of classic neuronal tumors and is the immunohistochemical hallmark of MVNT. In summary, we identified the characteristic tumoral expression of HuC/HuD and doublecortin and the presence of abundant neuropil localized in MVNT tumor nodules, which exhibited widespread alpha-internexin expression. These results supported the presumption that MVNT is a distinct histopathological entity.

Embryonal tumor with multilayered rosettes of the fourth ventricle: case report.

Embryonal tumor with multilayered rosettes (ETMR) is a recently described pathological entity. These primitive central nervous system tumors harbor amplification of the 19q13.42 locus and resultant overexpression of the LIN28A protein. Although the WHO currently recognizes 3 distinct histopathological entities-embryonal tumor with abundant neuropil and true rosettes (ETANTR), ependymoblastoma, and medulloepithelioma-recent studies indicate that these tumors have a common molecular profile and clinical course and that they are now classified as a single entity. Here the authors present a case of ETMR located in the fourth ventricle in a 12-month-old boy. The histopathology featured areas of neuropil-like stroma and highly cellular foci with characteristic multilayered rosettes. The authors discuss the clinical, radiological, and histopathological findings in this case and compare them with data in previously published cases in the literature. A review of studies assessing the molecular mechanisms underlying these tumors is also presented.

Double Para-testicular Cellular Angiofibroma and Synchronous Testicular Microlithiasis.

Cellular angiofibroma is a rare benign mesenchymal tumor. Since first described by Nucci et al. in 1997 [1], this distinct histopathologic entity has been reported in a series of studies [2-4] and case reports [5-7]. The tumor is characterized by two principal components, cellular spindle cells and prominent blood vessels [1]. Mild cytologic atypia and a few mitotic figures have been demonstrated in some cases [2,4]. The tumor occurs mainly in the inguinoscrotal region in men [2-5,7]. The molecular pathogenesis of cellular angiofibroma is largely unknown, although retinoblastoma 1 (RB1) and forkhead box protein O1 (FOXO1) have been implicated in some cases [3,7]. Testicular microlithiasis is a relatively rare condition characterized by calcifications within the seminiferous tubules. Two different types of testicular microlithiasis, hematoxylin bodies and laminated calcifications, have been described [8]. Many laminated calcifications have been associated with atrophic seminiferous tubules or germ cell neoplasia [8,9]. Here, we present a case of double para-testicular cellular angiofibroma and synchronous testicular microlithiasis.

CASO 5-2015: Cryptogenic organizing pneumonia

Cryptogenic organizing pneumonia (COP) is a distinct histopathologic entity characterized byMasson bodies which are intraalveolar buds of granulation tissue; consisting of connective tissue and myofibroblasts. This pathologic pattern when present with the characteristic imaging and clinical features of COP defines the diagnosis of the disease. A specific etiology is not found. Treatment with corticosteroids results in a rapid clinical and imaging improvement but unfortunately relapses are common upon decreasing the dose or stopping the treatment. This case report describes a typical case of COP with the characteristic improvement with corticosteroid therapy and relapse upon treatment taper

Lymphocytic and Collagenous Colitis: Epidemiologic Differences and Similarities

It is unknown whether the subtypes of microscopic colitis (MC) represent distinct nosologic entities or related presentations of the same disease. Our aim was to search for epidemiologic differences among its various histopathologic subtypes. In a computerized database of 789,568 colon pathology reports, we compared the characteristics of 8,745 MC patients with those of the remaining population. MC was diagnosed as three distinct histopathologic subtypes: lymphocytic colitis (LC) in 51 %, collagenous colitis (CC) in 43 %, and incomplete colitis (IC) in 6 % of patients. Only 0.65 % was simultaneously diagnosed with more than one subtype of MC. The prevalence of all three subtypes showed an age-dependent rise, with the average age (SD) being 63.3 (14.3) years in LC, 66.4 (12.1) years in CC, and 67.3 (12.7) years in IC (p < 0.0001). There was a striking female predominance in all three subtypes, the female fraction being 72 % in LC, 82 % in CC, and 79 % in IC (p < 0.0001). All three subtypes showed similar geographic distributions among different US states. They were similarly associated with diarrhea and weight loss, the odds ratios for all MC being 45.92 (43.35-48.63) and 5.12 (4.68-5.60), respectively, compared to control patients without MC. All three subtypes also harbored significantly less colonic adenomas, the overall odds ratio being 0.11 (0.10-0.12). MC comes in three distinct histopathologic entities, which show striking similarities of their general epidemiologic features. The slight differences in their demographic characteristics could point at varying sets of environmental influences that affect the occurrence of subtypes.

Keratin 10‐positive orthokeratotic dysplasia: a new leucoplakia‐type precancerous entity of the oral mucosa

We investigated a group of oral mucosal lesions with characteristic hyperorthokeratotic foci, which we termed orthokeratotic dysplasia (OKD), to determine if it could be identified as a distinct histopathological entity. We screened 282 surgical specimens from 200 patients with oral leucoplakia-type squamous cell carcinoma (SCC) or carcinoma in situ (CIS). OKD was defined as an oral mucosal lesional focus in which hyperorthokeratosis was predominant in the presence of the granular cell layer. A total of 84 OKD foci from 62 cases found among the 200 SCC/CIS cases were analysed. According to its rete ridge shapes, OKD was classified into three subtypes: flat (14.3%), leg (63.1%) and intermediate (22.6%). Eighty per cent of OKD foci were adjacent to the main foci of SCC or CIS, and they were demarcated sharply from each other. Most of the OKD constituent cells were immunopositive for keratin 10, but not for keratins 13, 17 or 19. Numbers of Ki-67-positive cells in the first basal layer were greater in OKD than in normal epithelia. The findings indicate that OKD is a distinct variant of epithelial dysplasia related to malignancies, and hence that it is important to recognize its existence.