Prevalence of TERT Promoter Mutations in Orbital Solitary Fibrous Tumors.

The orbital manifestation of a solitary fibrous tumor (SFT) is exceptionally rare and poses specific challenges in diagnosis and treatment. Its rather exceptional behavior among all SFTs comprises a high tendency towards local recurrence, but it rarely culminates in metastatic disease. This raises the question of prognostic factors in orbital SFTs (oSFTs). Telomerase reverse transcriptase (TERT)-promoter mutations have previously been linked to an unfavorable prognosis in SFTs of other locations. We analyzed the prevalence of TERT promoter mutations of SFTs in the orbital compartment. We performed a retrospective, descriptive clinico-histopathological analysis of nine cases of oSFTs between the years of 2017 and 2021. A TERT promoter mutation was present in one case, which was classified with intermediate metastatic risk. Local recurrence or progress occurred in six cases after primary resection; no distant metastases were reported. Multimodal imaging repeatedly showed particular morphologic patterns, including tubular vascular structures and ADC reduction. The prevalence of the TERT promoter mutation in oSFT was 11%, which is similar to the prevalence of extra-meningeal SFTs of the head and neck and lower than that in other extra-meningeal compartments. In the present study, the TERT promoter mutation in oSFT manifested in a case with an unfavorable prognosis, comprising aggressive local tumor growth, local recurrence, and eye loss.

[Automation and application of robotics in the pathology laboratory]. / Automatisierung und Einsatz von Robotern im Pathologielabor.

Over the last 20 years, numerous technical innovations have been introduced to the histopathology laboratory, providing tools for improved standardization and occupational safety. Digital tracking serves as a backbone accompanying the workflow from labeling cassettes and slides to the final steps of preparation of whole slide images and archiving blocks and sections. Multifunctional devices eliminated time consuming manual work prone to mistakes and loss of materials. At present, collaborative robots take over manual work that was considered to be exclusive to humans. The advent of these new technologies is expected to ameliorate the increasing staffing shortage in the laboratory and on the side of histopathologists as well.

COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis.

BACKGROUND: The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism. CASE PRESENTATION: Here, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2). CONCLUSION: Our findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

Comparison of Total Immunoglobulin G in Ante- and Postmortem Blood Samples from Tissue Donors.

BACKGROUND: A serology testing for infectious diseases (HIV, hepatitis B and C, syphilis) is mandatory in tissue donors. In many donors postmortem blood is the only sample available. Even though serological tests and nucleic acid amplification tests (NAT) used are validated for postmortem blood, a characterization of those blood samples is not yet established. We therefore investigated the total immunoglobulin G (IgG) content in postmortem blood of tissue donors and compared it to a corresponding antemortem blood sample. METHODS: Ante- and postmortem blood samples were obtained from 100 consecutive tissue donors. The total IgG of all samples was measured using an immune-turbidometric test on the AU 480 Chemistry Analyzer (Beckman Coulter). RESULTS: The mean total IgG concentration of antemortem blood samples from all 100 donors was 8.9 g/L ± 3.7 g/L (median 8.9 g/L, range 1.5 to 23.8 g/L). In 80 donors the IgG concentration in the antemortem blood sample was within the normal range with values ≥6 g/L (mean 10.0 g/L ± 3.3 g/L, median 9.3 g/L,). The total IgG concentration of the postmortem blood samples was lower with 7.2 g/L ± 3.2 g/L (median 6.7 g/L, range 0.6 to 18.2 g/L). The difference between the values of the antemortem and postmortem blood samples was 1.7 g/L ± 2.6 g/L (16.3%) (median 1.6 g/L, range -7.7 to 10.1 g/L). In 36 donors this difference was less than 10%, in 23 it was between 10 and 25%, in 33 between 26 and 50%, and in 8 over 50%. In 57 donors the total IgG in the postmortem blood sample was within the normal range with ≥6 g/L, in 53 of them also the value of the antemortem blood sample was within the normal range. No correlation for total IgG was found regarding the donor characteristics (age, sex, disease) and the sample characteristics (hemolysis, postmortem time). CONCLUSION: Total IgG values in antemortem samples were below the lower limit of 6 g/L in 20% of the cases. Total IgG was significantly lower in the postmortem samples compared to the antemortem samples, while 57% were still above the lower limit. No correlation with the postmortem time could be found. This lowered IgG levels should be payed attention to when using postmortem blood for infectious serology testing. Additional NAT testing should be considered.

SARS-CoV-2 mRNA vaccination-induced immunological memory in human nonlymphoid and lymphoid tissues.

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

[Automation and the use of robots in the pathology laboratory : A journey through time and a consideration of efficiency]. / Automatisierung und der Einsatz von Robotern im Pathologielabor : Eine Zeitreise und Effizienzbetrachtung.

In the past 20 years, numerous technical innovations were introduced to the histopathology laboratory, providing tools for improved standardization and occupational safety. Digital tracking serves as a backbone accompanying the workflow from the labeling of cassettes and slides to the final steps of preparing whole slide images and archiving blocks and sections. Multifunctional devices eliminated time consuming manual work prone to mistakes and loss of materials. At present, collaborative robots take over manual work that was considered to be exclusive to humans. The advent of these new technologies is expected to ameliorate the increasing staffing shortage in the laboratory but also of histopathologists.

Solitary and small (≤3 mm) apical positive surgical margins are related to biochemical recurrence after radical prostatectomy.

OBJECTIVES: To evaluate the prognostic value of positive surgical margins (PSM) in radical prostatectomy (RPE) specimens in relation to multifocality, localization and size. METHODS: A total of 1036 patients who underwent RPE and staged pT2-3a,pN0,M0 were evaluated. None had received adjuvant or neoadjuvant therapy. All specimens were routinely processed by complete whole mount sectioning. Exact number, localization and size of PSM were reassessed, and patients were followed up for a mean of 60 months. RESULTS: A total of 267 patients (26%) showed PSM (20% pT2, 48% pT3a). Preoperative prostate-specific antigen, Gleason score (GS) and PSM were independent predictors of biochemical recurrence (BCR). BCR-free survival rates for patients with and without PSM were 59% and 80%, respectively (HR 2.1; P < 0.001). PSM were related to biochemical failure in pT2 and pT3a tumors (P = 0.001 and P = 0.015). A total of 64% of solitary PSM were apical. Multifocality, localization and size of PSM had no significant impact on BCR. CONCLUSIONS: Solitary apical and small PSM in RPE have a significant impact on BCR-free survival in localized stages.

Brown Bowel Syndrome: An Exceedingly Rare Condition with Longstanding Malabsorption and an Unusual Cause of Colon Pseudo-Obstruction.

Brown bowel syndrome (BBS) is an exceedingly rare condition usually associated with longstanding malabsorption of any etiology. As a result of vitamin E deficiency and subsequent mitochondrial degeneration due to oxidative stress induced by free radicals, lipofuscin granules accumulate in the smooth muscles of the gastrointestinal tract resulting in myopathy and dysmotility with underlying disease aggravation. The current study reports a BBS case in a 64-year-old female patient who had undergone jejunoileal bypass surgery as a bariatric procedure. The patient was admitted with signs of malabsorption and ileus in computed tomography imaging. Endoscopic workup revealed no stenosis or obstruction. The colon histologically showed periodic acid-Schiff-positive lipofuscin granules in the lamina muscularis mucosa consistent with BBS. The vitamin E level in the patient was extremely low. Moreover, clinical improvement was documented following high-dose substitution. BBS should be considered in patients with malabsorption of any cause especially with signs of gastrointestinal dysmotility. Vitamin E substitution may improve clinical status and prevent further deterioration.

Discrepancies between clinical diagnosis and hospital autopsy: A comparative retrospective analysis of 1,112 cases.

AIMS: The aim of this study was to compare discrepancies between diagnosed and autopsied causes of death in 1,112 hospital autopsies and to determine the factors causing this discrepancies. METHODS: 1,112 hospital autopsies between 2010 and 2013 were retrospectively studied. Ante-mortem diagnoses were compared to causes of death as determined by autopsy. Clinical diagnoses were extracted from the autopsy request form, and post-mortem diagnoses were assessed from respective autopsy reports. Variables, such as sex, age, Body Mass Index, category of disease, duration of hospital stay and new-borns were studied in comparison to discrepancy. P-values were derived from the Mann-Whitney U test for the constant features and chi-2 test, p-values < 0,05 were considered significant. RESULTS: 73.9% (n = 822) patients showed no discrepancy between autopsy and clinical diagnosis. The duration of hospitalisation (6 vs. 9 days) and diseases of the cardiovascular system (61.7%) had a significant impact on discrepancies. CONCLUSION: Age, cardiovascular diseases and duration of hospital stay significantly affect discrepancies in ante- and post-mortem diagnoses.

B cell depletion and signs of sepsis-acquired immunodeficiency in bone marrow and spleen of COVID-19 deceased.

OBJECTIVES: In coronavirus disease 2019 (COVID-19), the adaptive immune response is of considerable importance, and detailed cellular immune reactions in the hematological system of patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are yet to be clarified. METHODS: This study reports the morphological characterization of both bone marrow and spleen in 11 COVID-19 decedents with respect to findings in the peripheral blood and pulmonary SARS-CoV-2 burden. RESULTS: In the bone marrow, activation and left shift were found in at least 55% of patients, which was mirrored by peripheral anaemia, granulocytic immaturity and multiple thromboembolic events. Signs of sepsis-acquired immunodeficiency were found in the setting of an abscess-forming superinfection of viral COVID-19 pneumonia. Furthermore, a severe B cell loss was observed in the bone marrow and/or spleen in 64% of COVID-19 patients. This was reflected by lymphocytopenia in the peripheral blood. As compared to B cell preservation, B cell loss was associated with a higher pulmonary SARS-CoV-2 burden and only a marginal decrease of of T cell counts. CONCLUSIONS: The results of this study suggest the presence of sepsis-related immunodeficiency in severe COVID-19 pneumonia with superinfection. Furthermore, our findings indicate that lymphocytopenia in COVID-19 is accompanied by B cell depletion in hematopoietic tissue, which might impede the durability of the humoral immune response to SARS-CoV-2.

Opposing Wnt signals regulate cervical squamocolumnar homeostasis and emergence of metaplasia.

The transition zones of the squamous and columnar epithelia constitute hotspots for the emergence of cancer, often preceded by metaplasia, in which one epithelial type is replaced by another. It remains unclear how the epithelial spatial organization is maintained and how the transition zone niche is remodelled during metaplasia. Here we used single-cell RNA sequencing to characterize epithelial subpopulations and the underlying stromal compartment of endo- and ectocervix, encompassing the transition zone. Mouse lineage tracing, organoid culture and single-molecule RNA in situ hybridizations revealed that the two epithelia derive from separate cervix-resident lineage-specific stem cell populations regulated by opposing Wnt signals from the stroma. Using a mouse model of cervical metaplasia, we further show that the endocervical stroma undergoes remodelling and increases expression of the Wnt inhibitor Dickkopf-2 (DKK2), promoting the outgrowth of ectocervical stem cells. Our data indicate that homeostasis at the transition zone results from divergent stromal signals, driving the differential proliferation of resident epithelial lineages.

Causes of death and comorbidities in hospitalized patients with COVID-19.

Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has been associated with more than two million deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of pre-existing health conditions to death yet is missing, which can be reliably established by autopsy only. We performed full body autopsies on 26 patients that had died after SARS-CoV-2 infection and COVID-19 at the Charité University Hospital Berlin, Germany, or at associated teaching hospitals. We systematically evaluated causes of death and pre-existing health conditions. Additionally, clinical records and death certificates were evaluated. We report findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.

Incidence of acute type A aortic dissection in emergency departments.

Due to the symptoms, patients with acute type A aortic dissection are first seen by the ambulance service and diagnosed at the emergency department. How often an aortic dissection occurs in an emergency department per year has been studied. The incidence in the emergency department may be used as a quality marker of differential diagnostics of acute chest pain. A multi-institutional retrospective study with the municipal Berlin hospital chain Vivantes and its Department of Pathology and the Charité - University Medicine Berlin was performed. From the Berlin Hospital Society, the annual numbers of publicly insured emergency patients were obtained. Between 2006 and 2016, 631 aortic dissections were identified. The total number of patients treated in the emergency departments (n = 12,790,577) was used to calculate the "emergency department incidence." The autopsy data from six clinics allowed an estimate on how many acute type A aortic dissections remained undetected. Across all Berlin hospitals, the emergency department incidence of acute type A aortic dissection was 5.24 cases in 100,000 patients per year. In tertiary referral hospitals and, particularly, in university hospitals the respective incidences were markedly higher (6.7 and 12.4, respectively). Based on the autopsy results, about 50% of the acute type A aortic dissection may remain undetected, which would double the reported incidences. Among different hospital types the emergency department incidences of acute type A aortic dissection vary between 5.93/100,000 and 24.92/100,000. Aortic dissection; Incidence; Emergency Department; Epidemiology.

Biomechanical efficacy of contact lens-assisted collagen cross-linking in porcine eyes.

PURPOSE: Contact lens-assisted corneal cross-linking (CACXL) has been proposed for the cross-linking treatment in thin corneas. The aim of this study was to assess the biomechanical efficacy of this treatment. METHODS: Post-mortem porcine eyes were treated with standard cross-linking and with cross-linking placing a contact lens soaked with isoosmolar riboflavin solution on the debrided cornea with or without an adherent precorneal riboflavin film of up to 100 µm thickness. Three soft contact lenses (Air Optix Aqua, SofLens and Galifa) with different degrees of hydrophilic properties were tested. After cross-linking with a surface UVA irradiance of 3 mW/cm² for 30 min (fluence 5.4 J/cm²), a 400 µm deep anterior corneal flap was created using a lamellar rotating microkeratome. Biomechanical stress-strain measurements and thermal shrinkage tests were performed. RESULTS: In the Air Optix Aqua group (30% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 92.4% respectively 86.35% of the standard CXL value. In the SofLens group (59% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was 67.04% respectively 65.28% of the standard CXL value. In the Galifa group (72% hydration) without riboflavin film, Young's modulus and stress at 8% strain were increased significantly versus untreated controls and the effect was about 68.48% respectively 75.52% of the standard CXL value. In all samples with a precorneal riboflavin film under the contact lens, there was no significant biomechanical effect compared to the untreated controls. Similarly, in the hydrothermal experiments at 70°C, there was a typical mushroom pattern with increased resistance to thermal shrinkage in the anterior stroma after standard CXL, a markedly reduced mushroom effect using a riboflavin-soaked contact lens only and no effect with the use of a riboflavin-soaked contact lens plus a precorneal riboflavin film. CONCLUSION: The biomechanical effect of CACXL in porcine corneas is about one-third less than after standard CXL. The efficacy of CACXL might be improved by reducing or omitting the riboflavin film on the contact lens. Further risk assessment studies are necessary.

Morphologic features in the regenerating liver--a comparative intravital, lightmicroscopical and ultrastructural analysis with focus on hepatic stellate cells.

Different cell types play a role in the liver regeneration. The present study reveals morphological key steps of liver regeneration by correlating intravital, light, and electron microscopic with immunohistochemistry results focusing on hepatic stellate cells (HSCs). In Lewis rats, liver regeneration was induced by a 2/3-hepatectomy. Animals (n = 7 each) were killed after 0, 1, 2, 3, 4, 7, and 14 days. Morphological features were investigated by light microscopy, immunohistochemistry [alpha-smooth muscle actin (alpha-SMA), Desmin, vascular endothelial growth factor (VEGF)/VEGF receptor, Ki-67, ssDNA], intravital microscopy (sinusoid density, number of hepatocytes, and HSC), and electron microscopy focussed on cell-to-cell interactions. During liver regeneration, HSC were activated at day 3 showing a loss of autofluorescence and simultaneously an increased alpha-SMA expression and direct cell contact to hepatocytes. HSC activation was followed by increasing VEGF expression and sinusoid density. After 14 days, liver architecture and ultrastructure was restored and HSCs were deactivated showing decreased alpha-SMA expression as well as increased apoptosis and no more direct cell contact to hepatocytes. HSCs play a central role in the regenerating liver by governing angiogenesis and extracellular matrix remodeling. A direct cell contact to hepatocytes seems to be essential for HSC activation, whereas deactivation is accompanied by loosening of hepatocyte contact and increased apoptosis.

Wound healing in the rabbit cornea after corneal collagen cross-linking with riboflavin and UVA.

PURPOSE: This study was undertaken to investigate the wound healing process of the first 6 weeks after photodynamic cross-linking treatment in the rabbit cornea, using the photosensitizer riboflavin and UVA. METHODS: After removal of the central epithelium, the right corneas of 8 Chinchilla rabbits were cross-linked with a photosensitizing 0.1% riboflavin solution and UVA light (370 nm; irradiance, 3 mW/cm(2); dose, 5.4 J/cm(2)) for 30 minutes. Two animals were euthanized 3 days, 7 days, 4 weeks, and 6 weeks postoperatively. The corneas of the enucleated eyes were evaluated using 4-microm light microscopic sections with routine stains and avidin-biotin complex immunostaining with anti-alpha-smooth muscle actin. RESULTS: By day 3 after treatment, complete apoptotic damage and loss of the endothelial cells and the stromal keratocytes were found in the irradiated area through the entire thickness of the stroma. There was marked stromal edema (850 +/- 66 vs. 332 +/- 43 microm in the untreated controls; P < 0.01). The epithelium was already closed again. At the margins of the lesion, there was a mild inflammatory reaction with scattered macrophages, lymphocytes, and neutrophils. By day 7, the endothelium was already intact again, and keratocyte repopulation of the posterior stroma was noted. By week 4, the keratocyte repopulation of the anterior stroma was observed with some acellular areas between. By week 6, the cytoarchitecture of the cornea seemed normal again. By weeks 4 and 6, alpha-actin-positive keratocytes were identified, especially in the periphery of the irradiated area. CONCLUSIONS: After riboflavin/UVA cross-linking of rabbit cornea, a complete cell loss occurs in the irradiation area with an irradiance of 3 mW/cm(2). The cytotoxic damage is repaired by repopulation after approximately 4-6 weeks. A combination of cross-linking with other procedures such as the implantation of intracorneal rings should be performed only after a sufficient time interval of approximately 2 months, allowing cellular regeneration.

Human endogenous retrovirus rec interferes with germ cell development in mice and may cause carcinoma in situ, the predecessor lesion of germ cell tumors.

Germ cell tumors (GCTs) are among the most common malignancies in young men. We have previously documented that patients with GCT frequently produce serum antibodies directed against proteins encoded by human endogenous retrovirus (HERV) type K sequences. Transcripts originating from the env gene of HERV-K, including the rec-relative of human immunodeficiency virus rev, are highly expressed in GCTs. We report here that mice that inducibly express HERV-K rec show a disturbed germ cell development and may exhibit, by 19 months of age, changes reminiscent of carcinoma in situ, the predecessor lesion of classic seminoma in humans. This provides the first direct evidence that the expression of a human endogenous retroviral gene previously established as a marker in human germ cell tumors may contribute to organ-specific tumorigenesis in a transgenic mouse model.

Expression of vascular cell adhesion molecule-1 (CD 106) in normal and neoplastic human esophageal squamous epithelium.

Vascular cell adhesion molecule-1 (VCAM-1), a key receptor for the leukocyte-associated integrin (VLA4), is a crucial mediator of leukocyte adhesion and has co-stimulatory functions in inflammation at various organ sites. Specifically, VCAM-1/VLA4 interactions have been shown to play important roles in the setting of cutaneous immune responses, such as psoriatic lesions in humans and acute Graft-versus-Host-Disease in mice. VCAM-1 is generally expressed on activated endothelial cells in inflamed tissues, mediating endothelium-leukocyte interactions, leading to leukocyte diapedesis to the site of inflammation. We report novel and unexpected membrane expression of VCAM-1 in the basal squamous epithelial strata of the normal human esophagus and distinct patterns of epithelial expression in esophageal pathology. To further delineate the differential expression patterns of VCAM-1 in the esophageal epithelium, we examined specimens from squamous cell carcinoma (SCC), adenocarcinoma, and Barrett's columnar cell metaplasia. VCAM-1 was strongly expressed in squamous cell carcinoma, but not adenocarcinoma nor columnar epithelia in Barrett's esophagus. VCAM-1 expression was focally accentuated at sites characteristic of microscopic tumor invasion in SCC, pointing to a potential role of VCAM-1 in the development of metastasis. In addition, in vitro immunofluorescence studies using OE21 cells, an esophageal squamous epithelial cell line, displayed distinct VCAM-1 immunoreactivity confined to mitotic and dividing cells. Cell cycle arrest caused a significant decrease in VCAM-1 immunoreactivity in OE21 cells. These data suggest a previously unappreciated role for VCAM-1 in esophageal squamous epithelial homeostasis and pathology.

Sporadic EBV-associated lymphoepithelial salivary gland carcinoma with EBV-positive low-grade myoepithelial component.

Salivary gland lymphoepithelial carcinomas (LECs) are associated with Epstein-Barr virus (EBV) in endemic areas, whereas sporadic cases are usually EBV negative. We have studied two EBV-associated LECs from Caucasian patients for their EBV gene expression profile and their immunophenotype. Tumour cells of case 1 showed expression of EBNA1 only, corresponding to an EBV latency type I. Tumour cells of this case expressed various basal and glandular cytokeratins. In case 2, the LEC was accompanied by a low-grade spindle cell lesion with an immunophenotype of myoepithelial cells, whereas the high-grade tumour expressed cytokeratin (Ck) 8 only. In case 2, the high-grade tumour showed an EBV lantency II pattern with expression of EBNA1, LMP1 and LMP2A (latency II). The spindle cell lesion of this case was also EBV-infected and showed low levels of EBNA1 and LMP1 expression, while LMP2A was not detectable. The detection of EBV in both components of case 2 together with immunophenotypic evidence of transition between both components supports the notion that at least some LECs arise through a low-grade myoepithelial intermediate. Expression of LMP2A may be of therapeutic interest because it may make such cases amenable to immunotherapy with EBV-specific cytotoxic T cells.