Progressive multifocal leukoencephalopathy (PML) is a feared entity that occurs most frequently in conditions of extreme immunodeficiency. The diagnosis is often made long after the onset of symptoms ...due to the physicians' unfamiliarity, and the unavailability of diagnostic tests in some medical centers. Although the incidence of PML is decreasing among HIV patients with the advent of highly active antiretroviral therapy (HAART), in Brazil this entity is the fourth highest neurological complication among these patients. The authors present the case of a middle-aged man who tested positive for HIV concomitantly with the presentation of hyposensitivity in the face and the right side of the body, accompanied by mild weakness in the left upper limb. The clinical features worsened rapidly within a couple of weeks. The diagnostic work-up pointed to the working diagnosis of PML after brain magnetic resonance imaging; however, the detection of the John Cunningham virus (JCV) in the cerebral spinal fluid was negative. HAART was started but the patient died after 7 weeks of hospitalization. The autopsy revealed extensive multifocal patchy areas of demyelination in the white matter where the microscopy depicted demyelination, oligodendrocytes alterations, bizarre atypical astrocytes, and perivascular lymphocytic infiltration. The immunohistochemistry was positive for anti-SV40, and the polymerase chain reaction of the brain paraffin-embedded tissue was positive for JCV. The authors highlight the challenges for diagnosing PML, as well as the devastating outcome of PML among HIV patients.
Indolent NK-cell lymphoproliferative disorder of the gastrointestinal tract is a new provisional entity listed in the structure of the forthcoming fifth edition of the World Health Organization (WHO) ...Classification of Hematolymphoid Tumors. It was first named as “NK-cell enteropathy” and “Lymphomatoid gastropathy” by two independent series a decade ago. Molecular or cytogenetic studies have lent support to the clonal/neoplastic nature of this entity. Herein we add two of such cases that still challenge pathologists and were previously diagnosed as aggressive lymphomas of NK/T derivation.
Lemierre's syndrome (LS), described in detail in 1936, used to be a life-threatening entity until the advent of antibiotics. Tonsillitis or pharyngitis are the main primary infections and ...oropharyngeal anaerobic flora is the predominant etiology. However, other primary site infections, as well as other microbiological agents have been reported since the first description. Inflammatory symptoms in the neck and marked findings on physical examination predominate the majority of cases. Nonetheless, the authors report the case of a 54-year-old man with a history of dysphagia followed by cough, purulent expectoration, and fever. The bad condition of his dentition was noteworthy. During the diagnostic work-up, an ulcerated lesion in the uvula and a middle lobe pneumonia were disclosed. Streptococcus viridans was isolated from blood culture. On the fifth day of hospitalization, the patient died after a copious episode of hemoptysis. The autopsy findings depicted an abscess within a squamous cell carcinoma of the uvula, pharyngitis with carotid sheath spreading accompanied by pylephlebitis and thrombosis of the internal jugular vein up to the innominate vein, surrounded by an abscess in the mediastinum. Alveolar hemorrhage and pneumonia were also present. We conclude that the ulcerated carcinoma of the uvula housed an abscess, facilitated by the poor oral hygiene, which triggered LS and the descending mediastinitis. Pulmonary involvement was due to the septic embolism from the internal jugular vein. We would like to highlight the uvula abscess as the primary site of infection in this case of LS with S. viridans as the causative agent.
Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and ...characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD.
This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated.
Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion.
LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.
Cryptococcal infection is commonly seen in immunocompromised patients, although immunocompetent patients may also be infected. The pathogen's portal of entry is the respiratory tract; however, the ...central nervous system is predominantly involved. Pulmonary involvement varies from interstitial and alveolar infiltrations to large masses, which are frequently first interpreted as lung neoplasm. The diagnosis of pulmonary cryptococcosis, in these cases, is frequently challenging, which, in most cases, requires histopathological examination. The authors report the case of a young female patient who presented a 20-day history of chest pleuritic pain and fever at the onset of symptoms. HIV serology was negative and CD4 count was normal. The imaging work-up was characterized by a huge opacity in the left inferior pulmonary lobe with a wide pleural base. Computed tomography showed a heterogeneous mass involving the bronchial tree. Mediastinal involvement was poor, and there was a splenomegaly. The patient underwent an exploratory thoracotomy and inferior lobectomy. The histopathological examination revealed a cryptococcoma. As the serum antigenemia was positive, the patient was scheduled for long-term treatment with fluconazole. The authors call attention to including the cryptococcal infection in the differential diagnosis of lung mass, mainly when localized in the lung bases in immunocompetent patients.
Since 2022, monkeypox virus (MPXV) has been causing a multinational epidemic with Brazil as one of the most affected countries.1,2 During the current mpox (formally known as monkeypox) epidemic, men ...with AIDS are at increased risk of severe illness and death, although it remains unclear whether deaths are directly attributed to MPXV.2 We report clinical and autopsy findings of two men in their early 20s, who had severe mpox associated with AIDS in São Paulo. The pathology of mpox described here is severe and includes new findings of visceral involvement by MPXV (figure and appendix pp 8–11).3–6 In both cases, autopsies showed anasarca, cavity effusions, and diffuse MPXV-mediated lesions in various organs confirmed by detectable vaccinia antigens and MPXV-DNA. Besides multiple MPXV-skin lesions with necrotic ulcers and MPXV-dermal vasculitis, the autopsies showed MPXV-induced bilateral necrotising nodular pneumonia, acute pleuritis with pleural effusion, nodular ulcerative gastrointestinal lesions, necrotic glossitis with vasogenic oedema, extensive proctitis, pancreatitis, sialoadenitis, orchitis (including germinative cells within seminiferous tubules), epididymitis, adrenalitis, and haemophagocytosis. ...in cases of HIV and MPXV coinfection, MPXV appears to be transmitted by a complex mechanism involving contact with infected skin and mucosa, and respiratory and sexual transmission, corroborating previous data on aerosol MPVX animal infection and MPXV–DNA detection in semen.8–12 These autopsies show previously undescribed findings in the pathology of human MPXV infection and are helpful to understand why people living with HIV or AIDS are under high risk for worse mpox-associated outcomes.13–15 We declare no competing interests.
Immunoglobulin IgG4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition with a characteristic histopathological appearance that can affect almost any organ. The clinical ...features result from a focal or diffuse appearance of a tumor-like swelling of the affected organs, identified by physical and/or imaging examination. Herein, we report the case of a 38-year-old male complaining of a worsening chronic right lumbar pain associated with legs and scrotum edema. He also had itchy and erythematous cutaneous lesions on the abdominal wall over the last 8 months, and complained of a diffuse and mild to moderate abdominal discomfort. On examination, the liver was firmly enlarged and tender. His legs had 2+ symmetrical pitting edema extending from his feet to just above the knees. An abdominal computed tomography scan showed a large mass (10 x 8 x 4cm) involving the abdominal infrarenal aorta and the iliac arteries, and compressing the inferior vena cava, with dilated iliac veins, raising the possibility of lymphoproliferative disease. During the initial investigation, the laboratory workup revealed anemia, without other marked changes. A laparoscopic-guided biopsy of the peri-aortic mass was undertaken. The histological report associated with IgG4 immunoglobulin measurement rendered the diagnosis of IgG4-RD. The patient had a favorable outcome after the use of glucocorticoids with the abdominal mass remission.
Streptococcus agalactiae is a well-known pathogen during pregnancy and in neonates. Among non-pregnant adults, invasive infection, although rare, is showing increasing frequency, especially in ...chronically ill, immunosuppressed, or older patients. Although rare, the clinical features of meningeal infection caused by S. agalactiae are similar to other bacterial meningitis. The authors report the case of a middle-aged man previously diagnosed with hypertension, diabetes mellitus, and alcoholic liver cirrhosis, who was admitted at the emergency department with a Glasgow Coma Scale of 11/12, generalized spasticity, bilateral Babinski sign, and hypertension. The clinical outcome was bad, with refractory shock and death within 24 hours of hospitalization. The bacteriological work-up isolated S. agalactiae in the cerebral spinal fluid (CSF), blood, and urine. An autopsy revealed meningoencephalitis, acute myocardial infarction, and pyelonephritis due to septic emboli. The authors point out the atypical CSF findings, the rapid fatal outcome, and the importance of including this pathogen among the etiologic possibilities of invasive infections in this group of patients.
Introduction: Follicular lymphoma (FL) is the most common low-grade B-cell NHL, encompassing 20-25% of all NHLs. Although classically indolent, it has heterogeneous biological behavior and variable ...clinical outcomes. Histologic transformation (HT) to high-grade B-cell NHL compose its natural history, being associated with dismal survival. The therapeutic management of FL and its prognosis are highly dependent on its staging and tumor burden. Based on this premise, the present study aims to describe clinical-laboratory characteristics, assess outcomes, determine predictors of survival and HT, and compare responses between different therapeutic strategies applied in a large cohort of FL patients. Methods: This retrospective and single-center study involved 223 patients with FL grades 1-3A, diagnosed at the University of São Paulo, Brazil, from 2006 to 2022. FL patients were categorized into early-stage disease (I/II) (ES), advanced-stage (AS) (III/IV) with low tumor burden (LTV), and AS with high tumor burden (HTV) according to the GELF criteria. Endpoints included OS, PFS, early-relapse (< 24 months from diagnosis) and HT rates. Survival curves were constructed using the Kaplan-Meier method and the Log-Rank test was used to assess the relationship between variables and outcomes. Univariate analysis was performed using the Cox test and multivariate analysis by Cox regression method or proportional ratios model. The results were presented in HR and 95% CI, and a p-value ≤ 0.05 was considered statistically significant. Results: The median age at diagnosis was 60 years (30-98) and 54.8% (121/223) were female. Approximately 15% of cases (33/223) had ES, 18.4% (41/224) had AS-LTV, and 66.8% (149/223) had AS-HTV. BM involvement, leukemic presentation, splenomegaly, and serous effusions occurred in 48.9% (109/223), 11.7% (26/223), 12.6% (28/223), and 21.1% (47/223), respectively. Bulky ≥ 7 cm, B-symptoms, ECOG ≥ 2, and involvement of ≥ 4 nodal areas were observed in 44.4% (99/223), 51.6% (115/223), 15.2% (34/223), and 56% (125/223), respectively - Table 1. Forty-nine percent of patients (110/223) were categorized as high-risk according to the FLIPI score. Table 2 summarizes the main outcomes and up-front therapeutic modalities applied in the whole cohort. With a median follow-up of 79.5 months (95% CI: 67.0-92.0) the OS medians were 18 years (95% CI: 14.9-21.1), 11 years (95% CI: 9.2-12.9), and 10.5 years (95% CI: 9.3-11.8) for ES, AS-LTV, and AS-HTV, respectively, p=0.138 Figure 1A. Similarly, the PFS medians were 6.7 years (95% CI: 3.6-9.8), 8.4 years (95% CI: 2.0-14.8), and 3.5 years (95 CI: 1.8-5.3) for ES, AS-LTV, and AS-HTV, respectively, p=0.171 Figure 1B. Early-relapses occurred in 36.3% (81/223) of cases, being 18.2% (6/33), 31.7% (13/41), and 41.0% (62/149) for ES, AS-LTV, and AS-HTV, respectively, p=0.032 Table 2. The overall mortality rate was 29.1% (65/223) for the whole cohort. HT was documented in 16.7% (37/223) of cases, being 3.0% (1/33), 14.6% (6/41) and 20.1% (30/149) for ES, AS-LTV, and AS-HTV, respectively, p=0.053 Table 2. Among patients with AS-HTV, the R-CHOP regimen did not promote increased OS compared to the R-CVP regimen (p=0.415), however it was associated with a substantial increase in PFS (p=0.005) Figure 2. Age ≥ 60 years (HR: 1.06, p<0.001), ≥ 2 comorbidities (HR: 3.85, p=0.014), B-symptoms (HR: 2.35, p=0.015), HT (HR: 2.77, p=0.002) and thrombocytopenia (HR: 2.96, p=0.028) were predictors of poor OS. Similarly, age ≥ 60 years (HR> 1.08, p<0.001), involvelment of ≥ 4 nodal areas (HR: 1.27, p<0.001), and high LDH levels (HR: 1.65, p=0.002) predicted decreased PFS. Additionally, serous effusions (HR: 2.09, p=0.05), albumin < 3.5 g/dL (HR: 2.82, p=0.05), B-symptoms (HR: 2.00, p=0.006), involvement of ≥ 4 nodal areas (HR: 1.21, p=0.014), and BM infiltration (HR: 2.11, p=0 .05) were the main predictors for HT. Conclusion: Although it is characteristically an indolent disease, our study demonstrated that a significant portion of FL patients have shortened survival. Here, we confirmed this prognostic heterogeneity, particularly considering the clinical staging and tumor burden. Therefore, FL patients with AS-HTV had higher HT rates and early-relapses, both classic adverse prognostic markers, as well as a tendency to higher mortality. We also identified clinical and laboratory predictors for HT, which may in a near future direct adapted-risk therapeutic strategies.
The symptoms of a previously healthy 14-year-old female with an initial history of tooth pain and swelling of the left maxillary evolved to a progressive headache and altered neurological findings ...characterized by auditory hallucinations, sleep disturbances, and aggressiveness. She was brought to the emergency department after 21 days of the initial symptoms. An initial computed tomography (CT) scan showed frontal subdural empyema with bone erosion. The symptoms continued to evolve to brain herniation 24 hours after admission. A second CT scan showed a left internal jugular vein thrombosis. The outcome was unfavorable and the patient died on the second day after admission. The autopsy findings depicted rarefaction of the cranial bone at the left side of the frontal sinus, and overt meningitis. The severe infection was further complicated by thrombophlebitis of the left internal jugular vein up to the superior vena cava with septic embolization to the lungs, pneumonia, and sepsis. This case report highlights the degree of severity that a trivial infection can reach. The unusual presentation of the sinusitis may have wrongly guided the approach of this unfortunate case.
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