Intrathecal Methotrexate-Induced Necrotizing Myelopathy: A Case Report and Review of Histologic Features

Central nervous system (CNS) relapse of acute lymphoblastic leukemia (ALL) is associated with a poor prognosis. However, prophylactic measures, including intrathecal (IT) methotrexate, reduce the incidence of CNS relapse in these patients considerably. Unfortunately, IT methotrexate can cause several neurologic complications, including transverse myelopathy; ie, the development of isolated spinal cord dysfunction over hours or days following the IT infusion of methotrexate, but in the absence of a compressive lesion. Transverse myelopathy following IT methotrexate is a well-established clinical phenomenon, but the histologic features have been described only very rarely. We report the autopsy findings from a 31-year-old man with a history of T-cell ALL who received prophylactic IT methotrexate in anticipation of a bone marrow transplant. Microscopic examination showed transverse necrosis of the thoracic cord, with massive infiltration by macrophages and lymphocytes, and perivascular lymphocytic infiltrates. There was cavitary necrosis of cervical and lumbar spinal cord involving the entire gray matter and focal white matter, as well as extensive subpial vacuolar degeneration of the dorsal and lateral columns.

Autopsy Patients With Obesity or Metabolic Syndrome as Basic Cause of Death: Are There Pathological Differences Between These Groups?

Background: The objectives of this study were the evaluation of pathological characteristics of patients with obesity or metabolic syndrome (MS) as basic cause of death, associating the autopsy findings with some clinical aspects and the abdominal adipose panicle thickness. Methods: A total of 88 autopsy cases were studied, divided into 2 groups based on the main cause of death: group 1 (n = 15) obesity and group 2 (n = 73) MS. Clinical summaries of autopsy requests, macroscopic findings, and histologic sections were reviewed. Results: The definition of obesity as the basic cause of death is associated with larger thickness of the abdominal adipose panicle, being 8.5 cm ( P = .001) the best measurement, according to the receiver operating characteristic curve. Hypertensive cardiopathy ( P = .001), ischemic cardiopathy ( P = .003), coronary ( P = .008)/systemic ( P = .005) atherosclerosis, and arterial ( P = .014)/arteriolar ( P = .027) nephrosclerosis are associated with the diagnosis of MS. Steatohepatitis is associated with the diagnosis of obesity ( P = .030); however, its association with the thickness of the abdominal adipose panicle is not statistically significant ( P = .211). Conclusions: In the context of an obese patient in autopsy, pathologist may use the information about abdominal adipose panicle associated with heart, kidney, and liver findings, even macroscopic ones, to decide the basic cause death between obesity and MS.

A Colonic Perineurioma

Perineurioma is a mesenchymal neoplasm best known in soft-tissue pathology. A colonic perineurioma is a relatively recently described entity and sometimes encountered in specimens from the large intestine, especially distal colon. Without its recognition, a perineurioma can be misdiagnosed as other more common gastrointestinal spindle cell neoplasms. Here, we describe a case of colonic perineurioma with polypoid growth extruding into the intestinal lumen. Case. A woman in her seventh decade of life underwent a follow-up colonoscopy after an uneventful resection of a benign colonic polyp. A previously undetected 6-mm polyp was found in the sigmoid colon and was resected endoscopically. Microscopic examination of the lesion revealed a proliferation of bland spindle cells in the lamina propria mucosae, which were immunohistochemically positive for epithelial membrane antigen, claudin 1, and glucose transporter-1. A colonic perineurioma was diagnosed.

Tubular Adenoma of the Breast: A Clinicopathologic Study of a Series of 9 Cases

Tubular adenoma of the breast is one of the most rare benign neoplasms, accounting for only 0.13% to 1.7% of all breast benign tumors. Little is known about this rare neoplasm as the current literature offers only some case reports or a few number of small series. The aim of our study is to provide some clinicopathologic features of the breast tubular adenoma. We retrospectively analyzed at our department of pathology all cases of breast tubular adenomas confirmed by immunohistochemistry over a period of 9 years (2009-2017). Nine cases of breast tubular adenoma have been recorded, with an average age of 31.44 years. Five tumors were located at the right side (55.55%), and most cases had suspicious aspects on imaging techniques (6 cases out of 9). The diagnosis has been made on 5 resected specimens (lumpectomy) and on 4 core needle biopsies. The tumor size ranged from 0.9 to 7 cm (mean size of 3.08 cm) and had well-circumscribed margins with elastic consistency. The histopathologic analysis showed a typical pattern of proliferating round and uniform tubules lined by regular epithelial cells surrounded by myoepithelial cells, packed in a small amount of stroma, highlighted by CD34 immunostaining. Tubular adenoma is a rare breast benign neoplasm of young premenopausal women. The radiologic aspects are often worrisome and only the histopathologic analysis can achieve the correct definitive diagnosis by excluding all potential differential diagnoses.

Is Tolerance Broken in Autoimmunity?

Autoimmune diseases are classified into about 80 different types based on their specificity related to system, organ and/or tissue. About 5% of the western population is affected by this anomaly, but its worldwide incidence is unknown. Autoimmune diseases are heterogeneous in nature and clinical manifestations range from benign disorders to life-threatening conditions. Autoimmunity strikes at any stage of life, but age and/or gender also play role in onset of some of these anomalies. The autoimmune pathogenesis is initiated by the origination of autoantigens, which leads to the development of autoantibodies followed by auto-immunogenicity and the ultimate onset of autoimmunity. There is a lack of suitable therapies to treat autoimmune diseases, because mechanisms involved in the onset of these anomalies were poorly understood. Present therapies are limited to symptomatic treatment and come with severe side effects. Here, I described the molecular mechanisms and cellular events involved in the initiation of autoimmunity and proposed better strategies to modulate such molecular and cellular anomalies, which will help in preventing and/or controlling autoimmune pathogenesis and ultimately aid in enhancing the quality of life.

Effects of Prolonged Treatment With Co-trimoxazole on the Thyroid Gland, Liver, and Epididymal Sperm Reserve in Dogs

Co-trimoxazole is an antimicrobial drug gotten from potentiation of sulfamethoxazole with trimethoprim. It is widely used for the treatment of bacterial and protozoan infections in humans. It is also used in veterinary clinics against susceptible microorganisms, but thyroid dysfunction has raised concern especially in dogs. This study aimed to determine the effects of prolonged treatment with co-trimoxazole in euthyroid dogs. Dogs were given co-trimoxazole at 30, 60, and 120 mg/kg body weight at 12-hour intervals for 21 days. Standard procedures were used to assay total T4 and T3, thyrotropin, testosterone, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase in serum. The thyroid gland and testes were weighed. In addition, thyroid and liver were examined histologically. Epididymal sperm count was also performed. Co-trimoxazole caused dose-dependent depression of serum thyroxine levels with severe colloid depletion, intrafollicular hemorrhage, hyperplasia, and hypertrophy of the follicular cells. The liver showed vacuolar hepatopathy. Epididymal sperm count was low in the 120 mg/kg–treated group. The study revealed that thyroid hemorrhage and lowered epididymal sperm reserve were new findings in co-trimoxazole toxicity in dogs.

Hanging Fatalities in Central Bangkok, Thailand: A 13-Year Retrospective Study

Hanging is violent asphyxial death. The objective of this study is to assess the data of hanging cases. A descriptive-retrospective study was conducted. We studied 244 hanging cases autopsied in Forensic Division, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, between January 2001 and December 2013. The study included 197 men (80.7%) and 47 women (19.2%). Their age ranged from 14 to 93 years. Most of these cases were incomplete hanging (83.6%). Features of hanging victims, such as tongue protrusion; congestion of face; petechial hemorrhage of face, conjunctiva, and internal organs; and neck injuries, significantly correlated with complete hanging. The predominant occupation of hanging victims was in the service industry (63.1%). Suicides usually occurred in private homes or apartments (84.8%). A suicide note was found in 6.1% of cases. The most common ligature material used was nylon rope, found in 61.1% of cases. The most underlying diseases of the victims in hanging cases were tuberculosis and human immunodeficiency virus infection, 9 cases each. Blood ethanol levels of 29 cases (11.8%) were detected to be higher than 150 mg%. Methamphetamine and benzodiazepine were detected in 5.3% and 3.3% of cases, respectively. This study provides comprehensive baseline data of hanging cases in central Bangkok.

A Little Help From the Follicles: Understanding the Germinal Center Response to Human Immunodeficiency Virus 1 Infection and Prophylactic Vaccines

Human immunodeficiency virus 1 (HIV-1) is the causative agent of AIDS. There are currently more than 35 million people living with HIV infection worldwide, and more than 2 million new infections occur each year. The global pandemic caused by HIV-1 is the subject of numerous research projects, with the development of a prophylactic vaccine and a therapeutic cure being the ultimate goals. The classic paradigms of vaccinology have proven incapable of producing a viable vaccine due to the complexity of the virus’ replication cycle, its genetic diversity, and a lack of understanding of the immune correlates of protection. Here, we briefly discuss recent vaccine approaches and the immune correlates of protection from HIV-1 infection with a focus on the role of the germinal center as a reservoir of replication-competent virus and its role in the development of broadly neutralizing antibodies in response to vaccination.

Impact of Pathology Review for Decision Therapy in Localized Prostate Cancer

Background: The Gleason score is an essential tool in the decision to treat localized prostate cancer. However, experienced pathologists can classify Gleason score differently than do low-volume pathologists, and this may affect the treatment decision. This study sought to assess the impact of pathology review of external biopsy specimens from 23 men with a recent diagnosis of localized prostate cancer. Methods: All external biopsy specimens were reviewed at our pathology department. Data were retrospectively collected from scanned charts. Results: The median patient age was 63 years (range: 46-74 years). All patients had a Karnofsky performance score of 90% to 100%. The median prostate-specific antigen level was 23.6 ng/dL (range: 1.04-13.6 ng/dL). Among the 23 reviews, the Gleason score changed for 8 (35%) patients: 7 upgraded and 1 downgraded. The new Gleason score affected the treatment decision in 5 of 8 cases (62.5%). Conclusions: This study demonstrates the need for pathology review in patients with localized prostate cancer before treatment because Gleason score can change in more than one-third of patients and can affect treatment decision in almost two-thirds of recategorized patients.

Functional Studies of CCAAT/Enhancer Binding Protein Site Located Downstream of the Transcriptional Start Site

Previous studies have identified a CCAAT/enhancer binding protein (C/EBP) site located downstream of the transcriptional start site (DS3). The role of the DS3 element with respect to HIV-1 transactivation by Tat and viral replication has not been characterized. We have demonstrated that DS3 was a functional C/EBPβ binding site and mutation of this site to the C/EBP knockout DS3-9C variant showed lower HIV-1 long terminal repeat (LTR) transactivation by C/EBPβ. However, it was able to exhibit similar or even higher transcription levels by Tat compared to the parental LTR. C/EBPβ and Tat together further enhanced the transcription level of the parental LAI-LTR and DS3-9C LTR, with higher levels in the DS3-9C LTR. HIV molecular clone viruses carrying the DS3-9C variant LTR demonstrated a decreased replication capacity and delayed rate of replication. These results suggest that DS3 plays a role in virus transcriptional initiation and provides new insight into C/EBP regulation of HIV-1.