Burkholderia gladioli deep pyoderma in a dog secondary to immunosuppressive ciclosporin and prednisone therapy.

A dog presented with deep pyoderma on the paw, following treatment with ciclosporin and prednisone for immune-mediated haemolytic anaemia. Cytological evaluation, skin biopsy, aerobic culture, next-generation DNA sequencing and PCR were used to detect the first reported case of Burkholderia gladioli in a dog.

Pathology and Monkeypox virus Localization in Tissues From Immunocompromised Patients With Severe or Fatal Mpox.

BACKGROUND: Pathology and Monkeypox virus (MPXV) tissue tropism in severe and fatal human mpox is not thoroughly described but can help elucidate the disease pathogenesis and the role of coinfections in immunocompromised patients. METHODS: We analyzed biopsy and autopsy tissues from 22 patients with severe or fatal outcomes to characterize pathology and viral antigen and DNA distribution in tissues by immunohistochemistry and in situ hybridization. Tissue-based testing for coinfections was also performed. RESULTS: Mucocutaneous lesions showed necrotizing and proliferative epithelial changes. Deceased patients with autopsy tissues evaluated had digestive tract lesions, and half had systemic tissue necrosis with thrombotic vasculopathy in lymphoid tissues, lung, or other solid organs. Half also had bronchopneumonia, and one-third had acute lung injury. All cases had MPXV antigen and DNA detected in tissues. Coinfections were identified in 5 of 16 (31%) biopsy and 4 of 6 (67%) autopsy cases. CONCLUSIONS: Severe mpox in immunocompromised patients is characterized by extensive viral infection of tissues and viremic dissemination that can progress despite available therapeutics. Digestive tract and lung involvement are common and associated with prominent histopathological and clinical manifestations. Coinfections may complicate mpox diagnosis and treatment. Significant viral DNA (likely correlating to infectious virus) in tissues necessitates enhanced biosafety measures in healthcare and autopsy settings.

Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022.

BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None.

Canine leproid granuloma caused by a member of the Mycobacterium tuberculosis complex.

Canine leproid granuloma (CLG) is a chronic form of dermatitis that has been associated with nontuberculous mycobacterial infections in Africa, Oceania, the Americas, and Europe. We report here a case of CLG associated with a member of the Mycobacterium tuberculosis complex (MTBC), which could be of public health concern. An 8-y-old pet dog developed 0.5-1-cm diameter, raised, firm, nonpruritic, alopecic, painless skin nodules on the external aspects of both pinnae. Histologic examination revealed severe pyogranulomatous dermatitis with intracellular Ziehl-Neelsen-positive bacilli that were immunoreactive by immunohistochemistry using a polyclonal primary antibody that recognizes tuberculous and nontuberculous Mycobacterium species. DNA extracted from formalin-fixed, paraffin-embedded skin sections was tested by a Mycobacterium genus-specific nested PCR assay targeting the 16S rRNA gene. BLAST sequence analysis of 214-bp and 178-bp amplicons showed 99.5% identity with members of the MTBC; however, the agent could not be identified at the species level. Although CLG has been associated traditionally with nontuberculous mycobacterial infections, the role of Mycobacterium spp. within the MTBC as a cause of this condition, and the role of dogs with CLG as possible sources of MTBC to other animals and humans, should not be disregarded given its zoonotic potential.

Acute liver failure and unique challenges of pediatric liver transplantation amidst a worldwide cluster of adenovirus-associated hepatitis.

Investigation into a recent cluster of acute hepatitis in children from the southeastern United States identified human adenovirus (HAdV) DNAemia in all 9 cases. Molecular genotyping in 5 of 9 (56%) children identified HAdV type 41 in all cases (100%). Importantly, 2 children from this cluster progressed rapidly to pediatric acute liver failure (PALF) and required liver transplantation. HAdV type 41, a known cause of self-limited gastroenteritis, has not previously been associated with severe cholestatic hepatitis and liver failure in healthy children. Adenovirus polymerase chain reaction assay and sequencing of amplicons performed on DNA extracted from formalin-fixed, paraffin-embedded liver tissue also identified adenovirus species F (HAdV type 40 or 41) in these 2 children with PALF. Transplant considerations and successful liver transplantation in such situations remain scarce. In this report, we describe the clinical course, laboratory results, liver pathology, and treatment of 2 children with PALF associated with HAdV type 41, one of whom developed secondary hemophagocytic lymphohistiocytosis. Their successful posttransplant outcomes demonstrate the importance of early multidisciplinary medical management and the feasibility of liver transplantation in some children with PALF and HAdV DNAemia.

A Case Series of Children with Acute Hepatitis and Human Adenovirus Infection.

BACKGROUND: Human adenoviruses typically cause self-limited respiratory, gastrointestinal, and conjunctival infections in healthy children. In late 2021 and early 2022, several previously healthy children were identified with acute hepatitis and human adenovirus viremia. METHODS: We used International Classification of Diseases, 10th Revision, codes to identify all children (<18 years of age) with hepatitis who were admitted to Children's of Alabama hospital between October 1, 2021, and February 28, 2022; those with acute hepatitis who also tested positive for human adenovirus by whole-blood quantitative polymerase chain reaction (PCR) were included in our case series. Demographic, clinical, laboratory, and treatment data were obtained from medical records. Residual blood specimens were sent for diagnostic confirmation and human adenovirus typing. RESULTS: A total of 15 children were identified with acute hepatitis - 6 (40%) who had hepatitis with an identified cause and 9 (60%) who had hepatitis without a known cause. Eight (89%) of the patients with hepatitis of unknown cause tested positive for human adenovirus. These 8 patients plus 1 additional patient referred to this facility for follow-up were included in this case series (median age, 2 years 11 months; age range, 1 year 1 month to 6 years 5 months). Liver biopsies indicated mild-to-moderate active hepatitis in 6 children, some with and some without cholestasis, but did not show evidence of human adenovirus on immunohistochemical examination or electron microscopy. PCR testing of liver tissue for human adenovirus was positive in 3 children (50%). Sequencing of specimens from 5 children showed three distinct human adenovirus type 41 hexon variants. Two children underwent liver transplantation; all the others recovered with supportive care. CONCLUSIONS: Human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause admitted to Children's of Alabama from October 1, 2021, to February 28, 2022, but whether human adenovirus was causative remains unclear. Sequencing results suggest that if human adenovirus was causative, this was not an outbreak driven by a single strain. (Funded in part by the Centers for Disease Control and Prevention.).

Histopathology and localization of SARS-CoV-2 and its host cell entry receptor ACE2 in tissues from naturally infected US-farmed mink (Neovison vison).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disease in mink similar to human COVID-19. We characterized the pathological findings in 72 mink from US farms with SARS-CoV-2 outbreaks, localized SARS-CoV-2 and its host cellular receptor angiotensin-converting enzyme 2 (ACE2) in mink respiratory tissues, and evaluated the utility of various test methods and specimens for SARS-CoV-2 detection in necropsy tissues. Of SARS-CoV-2-positive animals found dead, 74% had bronchiolitis and diffuse alveolar damage (DAD). Of euthanized SARS-CoV-2-positive animals, 72% had only mild interstitial pneumonia or minimal nonspecific lung changes (congestion, edema, macrophages); similar findings were seen in SARS-CoV-2-negative animals. Suppurative rhinitis, lymphocytic perivascular inflammation in the lungs, and lymphocytic infiltrates in other tissues were common in both SARS-CoV-2-positive and SARS-CoV-2-negative animals. In formalin-fixed paraffin-embedded (FFPE) upper respiratory tract (URT) specimens, conventional reverse transcription-polymerase chain reaction (cRT-PCR) was more sensitive than in situ hybridization (ISH) or immunohistochemistry (IHC) for detection of SARS-CoV-2. FFPE lung specimens yielded less detection of virus than FFPE URT specimens by all test methods. By IHC and ISH, virus localized extensively to epithelial cells in the nasal turbinates, and prominently within intact epithelium; olfactory mucosa was mostly spared. The SARS-CoV-2 receptor ACE2 was extensively detected by IHC within turbinate epithelium, with decreased detection in lower respiratory tract epithelium and alveolar macrophages. This study expands on the knowledge of the pathology and pathogenesis of natural SARS-CoV-2 infection in mink and supports their further investigation as a potential animal model of SARS-CoV-2 infection in humans.

BK virus associated with small cell carcinoma of bladder in a patient with renal transplant.

A man in his 70s with a complex medical history, including cadaveric renal transplant, presented with recurrent urinary tract infections. Investigation revealed recurrent urinary pathogens, including Enterobacter cloacae and persistent BK viruria. Cystoscopy revealed a pedunculated mass in the right posterior-lateral wall, inferior to the transplant urethral orifice, and biopsy of this mass showed invasive small cell carcinoma with a prominent adenocarcinoma component. The tumour was treated with complete transurethral resection followed by carboplatin, etoposide and radiation. Laboratory analysis of biopsied samples showed immunostaining and molecular evidence of BK virus DNA in the cancer cells. Follow-up cystoscopies have shown no recurrence of the cancer.

Human Adenovirus 11 in 2 Renal Transplant Recipients: Suspected Donor-Derived Infection.

BACKGROUND: Human adenovirus (HAdV) infections can lead to high mortality in solid organ transplant (SOT) recipients, with rare reports of donor-derived infection. METHODS: Two renal transplant recipients with HAdV-11 infection who received kidneys from the same donor are described. Whole-genome sequencing (WGS) was performed. RESULTS: WGS showed 100% nucleotide sequence identity for the 2 HAdV-11 isolates. The patients presented with distinct clinical syndromes, and both were treated with brincidofovir. CONCLUSIONS: Donor-derived HAdV infection is presumed to be low; however, disseminated HAdV in SOT recipients can be severe, and clinicians should be aware of the clinical course and treatment options.

Detection of coxsackievirus A6 in formalin-fixed, paraffin-embedded skin biopsy specimens using immunohistochemistry and real-time reverse-transcriptase PCR.

Background: Hand, foot, and mouth disease (HFMD), classically a childhood viral infection, has an atypical and severe clinical presentation in adults. Coxsackievirus A6 is a leading cause of atypical HFMD, but current diagnostic methods utilizing formalin-fixed, paraffin-embedded skin biopsy specimens often lack sensitivity and specificity. Methods: Formalin-fixed, paraffin-embedded skin biopsies from seven case patients with clinical and histopathological suspicion of atypical HFMD were evaluated by coxsackievirus A6 (CVA6) immunohistochemistry, enterovirus-specific conventional reverse transcriptase-PCR with subsequent Sanger sequencing targeting the 5'UTR, and CVA6-specific real-time PCR targeting the VP1 gene. Results: The CVA6-specific antibody demonstrated appropriate antigen distribution and staining intensity in keratinocytes in all cases. Conventional RT-PCR and sequencing also detected the presence of enterovirus, and CVA6-specific real-time RT-PCR analysis identified CVA6. Conclusion: Applying these immunohistochemistry and molecular techniques to formalin-fixed, paraffin-embedded tissues, CVA6 was determined to be the causative infectious agent in seven cases of atypical hand, foot, and mouth disease.

Pathological findings in suspected cases of e-cigarette, or vaping, product use-associated lung injury (EVALI): a case series.

BACKGROUND: Since August, 2019, US public health officials have been investigating a national outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI). A spectrum of histological patterns consistent with acute to subacute lung injury has been seen in biopsies; however, autopsy findings have not been systematically characterised. We describe the pathological findings in autopsy and biopsy tissues submitted to the US Centers for Disease Control and Prevention (CDC) for the evaluation of suspected EVALI. METHODS: Between Aug 1, 2019, and Nov 30, 2019, we examined lung biopsy (n=10 individuals) and autopsy (n=13 individuals) tissue samples received by the CDC, submitted by 16 US states, from individuals with: a history of e-cigarette, or vaping, product use; respiratory, gastrointestinal, or constitutional symptoms; and either pulmonary infiltrates or opacities on chest imaging, or sudden death from an undetermined cause. We also reviewed medical records, evaluated histopathology, and performed infectious disease testing when indicated by histopathology and clinical history. FINDINGS: 21 cases met surveillance case definitions for EVALI, with a further two cases of clinically suspected EVALI evaluated. All ten lung biopsies showed histological evidence of acute to subacute lung injury, including diffuse alveolar damage or organising pneumonia. These patterns were also seen in nine of 13 (69%) autopsy cases, most frequently diffuse alveolar damage (eight autopsies), but also acute and organising fibrinous pneumonia (one autopsy). Additional pulmonary pathology not necessarily consistent with EVALI was seen in the remaining autopsies, including bronchopneumonia, bronchoaspiration, and chronic interstitial lung disease. Three of the five autopsy cases with no evidence of, or a plausible alternative cause for acute lung injury, had been classified as confirmed or probable EVALI according to surveillance case definitions. INTERPRETATION: Acute to subacute lung injury patterns were seen in all ten biopsies and most autopsy lung tissues from individuals with suspected EVALI. Acute to subacute lung injury can have numerous causes; however, if it is identified in an individual with a history of e-cigarette, or vaping, product use, and no alternative cause is apparent, a diagnosis of EVALI should be strongly considered. A review of autopsy tissue pathology in suspected EVALI deaths can also identify alternative diagnoses, which can enhance the specificity of public health surveillance efforts. FUNDING: US Centers for Disease Control and Prevention.

Respiratory Illness Associated With Emergent Human Adenovirus Genome Type 7d, New Jersey, 2016-2017.

BACKGROUND: Human adenoviruses (HAdVs) are known causes of respiratory illness outbreaks in congregate settings, but cases and clusters are less well described from community settings in the United States. During December 2016-February 2017, the New Jersey Department of Health received reports of HAdV infections from 3 sources in 3 adjacent counties. We investigated to characterize the epidemiologic, laboratory, and clinical features of this HAdV outbreak. METHODS: A case was defined as a New Jersey resident with acute respiratory illness during December 1, 2016-March 31, 2017 with laboratory identification of HAdV genome type 7d (HAdV-7d). Human adenovirus was detected by real-time and conventional polymerase chain reaction and molecular typed by partial hexon capsid protein gene sequencing. The HAdV genome type was identified by whole genome sequencing analysis. Available medical, public health, and surveillance records were reviewed. RESULTS: We identified 12 cases, including 3 treatment facility patients, 7 college students, and 2 cases at a tertiary-care hospital. Four cases died; all had underlying comorbidities. Nine HAdV-7d whole genome sequences obtained from all 3 sites were nearly identical. CONCLUSIONS: Transmission of HAdV-7d occurred in community and congregate settings across 3 counties and resulted in severe morbidity and mortality in some cases with underlying comorbidities. Clinicians and local and state health departments should consider HAdV in patients with severe respiratory infection.

Outbreak of Tattoo-associated Nontuberculous Mycobacterial Skin Infections.

BACKGROUND: On 29 April 2015, the Florida Department of Health in Miami-Dade County (DOH Miami-Dade) was notified by a local dermatologist of 3 patients with suspected nontuberculous mycobacterial (NTM) infection after receiving tattoos at a local tattoo studio. METHODS: DOH Miami-Dade conducted interviews and offered testing, described below, to tattoo studio clients reporting rashes. Culture of clinical isolates and identification were performed at the Florida Bureau of Public Health Laboratories. Characterization of NTM was performed by the Centers for Disease Control and Prevention and the US Food and Drug Administration (FDA), respectively. Whole-genome sequencing (WGS) and single-nucleotide polymorphism (SNP) analyses were used to construct a phylogeny among 21 Mycobacterium isolates at the FDA. RESULTS: Thirty-eight of 226 interviewed clients were identified as outbreak-associated cases. Multivariate logistic regression revealed that individuals who reported gray tattoo ink in their tattoos were 8.2 times as likely to report a rash (95% confidence interval, 3.1-22.1). Multiple NTM species were identified in clinical and environmental specimens. Phylogenetic results from environmental samples and skin biopsies indicated that 2 Mycobacterium fortuitum isolates (graywash ink and a skin biopsy) and 11 Mycobacterium abscessus isolates (5 from the implicated bottle of graywash tattoo ink, 2 from tap water, and 4 from skin biopsies) were indistinguishable. In addition, Mycobacterium chelonae was isolated from 5 unopened bottles of graywash ink provided by 2 other tattoo studios in Miami-Dade County. CONCLUSIONS: WGS and SNP analyses identified the tap water and the bottle of graywash tattoo ink as the sources of the NTM infections.

Mycobacterium chimaera Hepatitis: A New Disease Entity.

Mycobacterium chimaera was identified as a species within the Mycobacterium avium complex in 2004. Until recently, it was predominantly seen in immunocompromised patients. In 2015, an outbreak of disseminated M. chimaera disease was described in European patients after undergoing open-heart surgery in which contaminated heater-cooler water units were used. Using whole genomic sequencing and phylogenetic analysis, investigators found a highly clonal outbreak from the German manufacturing site of the heater-cooler water units. This outbreak has now proven to be world-wide. Patients present with fever, fatigue, and weight loss months to many years after surgery. They are found to have systemic manifestations, including endocarditis, pancytopenia, renal dysfunction, chorioretinitis, and hepatitis. Preliminary reports suggest a high mortality rate despite aggressive treatment. In some patients, the predominant laboratory abnormalities are elevations in liver function tests, leading to diagnostic hepatobiliary work-ups, including liver biopsy. The pathologic changes in the liver have not yet been described. Herein, we report the clinicopathologic findings of the largest series of M. chimaera liver disease in the United States to date: 7 cases within a large, multihospital health care network. Five (71%) patients died of disease, despite aggressive treatment. Liver function test abnormalities were predominantly biliary: mean values of alkaline phosphate 288 U/L, aspartate aminotransferase 79 U/L, alanine aminotransferase 64 U/L. All 7 biopsies showed a consistent and characteristic dual pattern of injury: small, ill-formed collections of sinusoidal histiocytes with rare multinucleated giant cells, and scattered architectural changes of venous outflow obstruction. Two (29%) cases showed mild pericellular fibrosis. Nodular regenerative hyperplasia was seen in 2 (29%) cases, consistent with a sinusoidal/venous obstructive pattern of injury. We postulate that the sinusoidal location of the granulomas contributes to the venous obstructive changes. Recognition of this characteristic dual pattern of injury can allow pathologists to suggest the diagnosis and prompt the appropriate diagnostic and therapeutic interventions.

Vital Signs: Update on Zika Virus-Associated Birth Defects and Evaluation of All U.S. Infants with Congenital Zika Virus Exposure - U.S. Zika Pregnancy Registry, 2016.

BACKGROUND: In collaboration with state, tribal, local, and territorial health departments, CDC established the U.S. Zika Pregnancy Registry (USZPR) in early 2016 to monitor pregnant women with laboratory evidence of possible recent Zika virus infection and their infants. METHODS: This report includes an analysis of completed pregnancies (which include live births and pregnancy losses, regardless of gestational age) in the 50 U.S. states and the District of Columbia (DC) with laboratory evidence of possible recent Zika virus infection reported to the USZPR from January 15 to December 27, 2016. Birth defects potentially associated with Zika virus infection during pregnancy include brain abnormalities and/or microcephaly, eye abnormalities, other consequences of central nervous system dysfunction, and neural tube defects and other early brain malformations. RESULTS: During the analysis period, 1,297 pregnant women in 44 states were reported to the USZPR. Zika virus-associated birth defects were reported for 51 (5%) of the 972 fetuses/infants from completed pregnancies with laboratory evidence of possible recent Zika virus infection (95% confidence interval [CI] = 4%-7%); the proportion was higher when restricted to pregnancies with laboratory-confirmed Zika virus infection (24/250 completed pregnancies [10%, 95% CI = 7%-14%]). Birth defects were reported in 15% (95% CI = 8%-26%) of fetuses/infants of completed pregnancies with confirmed Zika virus infection in the first trimester. Among 895 liveborn infants from pregnancies with possible recent Zika virus infection, postnatal neuroimaging was reported for 221 (25%), and Zika virus testing of at least one infant specimen was reported for 585 (65%). CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: These findings highlight why pregnant women should avoid Zika virus exposure. Because the full clinical spectrum of congenital Zika virus infection is not yet known, all infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy should receive postnatal neuroimaging and Zika virus testing in addition to a comprehensive newborn physical exam and hearing screen. Identification and follow-up care of infants born to women with laboratory evidence of possible recent Zika virus infection during pregnancy and infants with possible congenital Zika virus infection can ensure that appropriate clinical services are available.

Clinical and Pathological Evaluation of Mycobacterium marinum Group Skin Infections Associated With Fish Markets in New York City.

BACKGROUND: From December 2013 through May 2014, physicians, dermatopathologists, and public health authorities collaborated to characterize an outbreak of Mycobacterium marinum and other nontuberculous mycobacterial skin and soft tissue infections (SSTIs) associated with handling fish in New York City's Chinatown. Clinicopathologic and laboratory investigations were performed on a series of patients. METHODS: Medical records were reviewed for 29 patients. Culture results were available for 27 patients and 24 biopsy specimens were evaluated by histopathology, immunohistochemistry (IHC) staining for acid-fast bacilli (AFB), and mycobacterial polymerase chain reaction (PCR) assays. RESULTS: All patients received antibiotics. The most commonly prescribed antibiotic regimen was clarithromycin and ethambutol. Of the 29 patients in this case series, 16 (55%) received surgical treatment involving incision and drainage, mass excision, and synovectomy. Of these, 7 (44%) had deep tissue involvement. All patients showed improvement. For those with culture results, 11 of 27 (41%) were positive for M. marinum; the remainder showed no growth. Poorly formed granulomas (96%), neutrophils (75%), and necrosis (79%) were found in 24 biopsies. Of 15 cases that were culture-negative and analyzed by other methods, 9 were PCR positive for M. marinum group species, 8 were IHC positive, and 3 were positive by AFB stains. CONCLUSIONS: A multidisciplinary approach was used to identify cases in an outbreak of M. marinum infections. The use of histopathology, culture, and IHC plus PCR from full thickness skin biopsy can lead to improved diagnosis of M. marinum SSTIs compared to relying solely on mycobacterial culture, the current gold standard.

Malignant Transformation of Hymenolepis nana in a Human Host.

Neoplasms occur naturally in invertebrates but are not known to develop in tapeworms. We observed nests of monomorphic, undifferentiated cells in samples from lymph-node and lung biopsies in a man infected with the human immunodeficiency virus (HIV). The morphologic features and invasive behavior of the cells were characteristic of cancer, but their small size suggested a nonhuman origin. A polymerase-chain-reaction (PCR) assay targeting eukaryotes identified Hymenolepis nana DNA. Although the cells were unrecognizable as tapeworm tissue, immunohistochemical staining and probe hybridization labeled the cells in situ. Comparative deep sequencing identified H. nana structural genomic variants that are compatible with mutations described in cancer. Invasion of human tissue by abnormal, proliferating, genetically altered tapeworm cells is a novel disease mechanism that links infection and cancer.

Intraventricular granulomatous mass associated with Mycobacterium haemophilum: A rare central nervous system manifestation in a patient with human immunodeficiency virus infection.

We report a rare case of Mycobacterium haemophilum presenting as an intraventricular granulomatous mass with loculated hydrocephalus and seizures in a patient with human immunodeficiency virus. M. haemophilum, a slow-growing mycobacteria, causes localized and disseminated disease among immunocompromised hosts. Central nervous system infection with M. haemophilum is extremely rare. Preoperative laboratory testing of our patient for tuberculosis, toxoplasmosis, sarcoidosis and histoplasmosis were negative. Surgical resection of the mass revealed a caseating granuloma that stained positive for acid-fast bacillus suggesting possible tuberculoma. Despite negative testing for tuberculosis, a polymerase chain reaction analysis was ultimately performed from the resected mass which revealed M. haemophilum. To our knowledge, this is the first case of M. haemophilum presenting as an intraventricular mass. We review the clinical manifestations of this pathogen and discuss the medical and surgical management.

Tissue tropism, pathology and pathogenesis of enterovirus infection.

Enteroviruses are very common and cause infections with a diverse array of clinical features. Enteroviruses are most frequently considered by practising pathologists in cases of aseptic meningitis, encephalitis, myocarditis and disseminated infections in neonates and infants. Congenital infections have been reported and transplacental transmission is thought to occur. Although skin biopsies during hand, foot and mouth disease are infrequently obtained, characteristic dermatopathological findings can be seen. Enteroviruses have been implicated in lower respiratory tract infections. This review highlights histopathological features of enterovirus infection and discusses diagnostic modalities for formalin-fixed paraffin-embedded tissues and their associated pitfalls. Immunohistochemistry can detect enterovirus antigen within cells of affected tissues; however, assays can be non-specific and detect other viruses. Molecular methods are increasingly relied upon but, due to the high frequency of asymptomatic enteroviral infections, clinical-pathological correlation is needed to determine significance. Of note, diagnostic assays on central nervous system or cardiac tissues from immunocompetent patients with prolonged disease courses are most often negative. Histopathological, immunohistochemical and molecular studies performed on clinical specimens also provide insight into enteroviral tissue tropism and pathogenesis.