[Standard therapy of tuberculosis and its variants].
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In North America, endometrial cancer is the most prevalent cancer of the female genital tract. On the basis of clinical and histologic variables, two main types of endometrial cancer have been described: Type I tumors, which are usually well differentiated and endometrioid in histology and account for the majority of cases; and Type II, which are poorly differentiated tumors, often with serous papillary or clear cell histology. Due to the early declaration of the disease by vaginal bleeding, approximately 80% of endometrial cancers are diagnosed at an early stage. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymph node dissection remains the cornerstone of treatment. Tumor stage, histologic grade and depth of myometrial invasion are the most important prognostic factors. If myometrial invasion to 50% or more of the myometrial width and/or grade 2 or 3 histology is present, pelvic radiotherapy is indicated to reduce the risk of pelvic recurrence. Postoperative radiation therapy may improve local control but does not affect survival for Stage I endometrial cancer patients. Systemic chemotherapy is typically reserved for women with disseminated primary disease or extrapelvic recurrence. Although the combination of cisplatin plus doxorubicin is commonly used, carboplatin plus paclitaxel represents an efficacious, low-toxicity regimen for managing advanced or recurrent endometrial cancer. Recently, a significant percentage of Type II uterine tumors have been found to overexpress the epidermal growth factor Type II receptor. Anti-HER-2/neu-targeted therapy might be a novel and attractive therapeutic strategy in patients harboring this biologically aggressive variant of endometrial cancer.
BACKGROUND: The 2024-2026 US H5N1 clade 2.3.4.4b dairy cattle outbreak has been characterised primarily through consensus-level phylogenetics. Whether mammalian-adaptation variants are emerging at sub-consensus frequencies within infected hosts, particularly at the haemagglutinin receptor-binding domain (RBD), remains unknown because no systematic within-host variant analysis of the public sequencing corpus has been performed. METHODS: We conducted a pre-registered, corpus-wide intrahost single-nucleotide variant (iSNV) analysis of all publicly available H5N1 cattle, feline-spillover, and retail-milk sequences on the NCBI Sequence Read Archive (4559 samples across 7 BioProjects). A dual-caller concordance pipeline (iVar + LoFreq) with empirically determined allele frequency (AF) threshold (3%, set via four-criterion validation including synthetic spike-in controls) was applied to an 11-site Tier 1 mammalian-adaptation panel spanning the polymerase complex, haemagglutinin RBD, and accessory proteins. Within-host nucleotide diversity was compared across host categories. RESULTS: The HA RBD sites Q226L and G228S (H3 numbering) showed zero detections across >4300 adequately sequenced samples at all AF thresholds tested (1-5%), despite the pipeline detecting other non-synonymous variants at these exact codon positions (upper 95% CI for prevalence: 0.08%). Seven of eleven adaptation sites carried statistically significant iSNV signals after Bonferroni correction (corrected α = 0.00417), though all at low prevalence (≤2.95%). Genotype stratification showed that most polymerase-site detections reflected genotype structure rather than within-host emergence: the apparent PB2 631 L→M "reversion" was largely the ancestral avian state of the D1.1 genotype (20 of 23 detections), which never acquired the 631L mammalian adaptation, with only two genuine sub-consensus events in the B3.13 background, while consensus-level PB2 701N was a fixed feature of the D1.1 genotype (10 of 14 detections) rather than independent sub-consensus emergence. Cattle exhibited significantly higher within-host nucleotide diversity than feline-spillover samples (π = 1.59 × 10-4 vs 6.11 × 10-5; Kruskal-Wallis p = 6.6 × 10-15), a finding that persisted after depth-matching (p = 4.6 × 10-5); this may reflect prolonged mammary-gland infection, though sampling differences and host biology cannot be excluded. CONCLUSIONS: We did not detect HA receptor-switching adaptation (the acquisition of human-type α2,6 receptor binding via Q226L/G228S) at any tested allele frequency in the US dairy H5N1 outbreak. Sub-consensus mammalian-adaptation signals exist at polymerase-complex sites but at low prevalence, are genotype-structured rather than independently recurrent, and require functional characterisation before informing risk assessment.
The mucoepidermoid carcinoma is a very rare neoplasm of the breast which histologically resembles mucoepidermoid carcinoma in the salivary glands. It is characterized by sheets of epidermoid cells with area of definite squamous differentiation as well as glandular and cystic spaces lined by atypical mucin-secreting columnar cells. The ultrastructural findings reflect the squamous and adenomatous differentiation seen on light microscopy. The degree of histological differentiation and the infrequency of nodal metastasis suggest an indolent behaviour. This is supported by the absence of recurrence or death due to the disease in 7 of the 8 cases reported to date. Only 1 patient has had extensive axillary nodal metastasis from a mucoepidermoid carcinoma which showed large areas of poorly differentiated cells. The present case is another example of such a high grade variant in which death occurred from pulmonary and vertebral metastases within 6 mth of mastectomy. An aggressive behaviour should be predicted by the presence of a large undifferentiated component in the tumour, necrosis and prominence of mitoses.
The work was performed on a material of a non-randomized group of patients with attack-like schizophrenia registered (January 1976) at the psychoneurological dispensary of one of the districts of Moscow. Using the method of a clinico-epidemiological catamnesis as well as a definite method of determining the arrest of the process of attack formation in a group of patients, 641 patients could be distinguished. The condition of those patients was qualified as "outcome", "++post-morbid". The rate of such cases in the whole patients' group amounted to 62.5%. The data on the clinical structure of the outcomes, including productive psychopathological and negative symptomatology as well as the level of social and work adaptation of the patients enabled one to distinguish groups with a favourable outcome (471 cases) and unfavourable outcome (170 cases), which accounted for 46.0 and 16.6% of the entire non-randomized group of patients. Therefore, based on the populational regularities of the course of attack-like schizophrenia the authors succeeded in demonstrating a possibility of arresting the process of attack formation at any disease stage, to determine the rate of such cases in the patients' population as well as to objectively prove the domination of a favourable variant of outcome of the morbid process.
The surgical treatment of phyllodes tumors differs from that for fibroadenomas, with the former necessitating complete excision with no remaining neoplastic tissue to produce local recurrence. To determine whether we could predict the type of breast lesion on cytology we reviewed the cytological features of 39 fibroepithelial lesions, including ordinary fibroadenomas, fibroadenoma variants (intermediate group), benign phyllodes tumors, and malignant phyllodes tumors, which had a biopsy diagnosis and adequate cytology. We found no differences in the glandular elements, the myoepithelial and single stromal cells, and the type of stromal fragments seen in the three benign groups. The stromal nuclei, the number of leaf-shaped fragments, and the numbers of spindle-cell groups present showed a spectrum of changes varying from those of fibroadenomas at one end to those of benign phyllodes tumors at the other. Malignant phyllodes tumors had characteristic features which were quite different from those of the benign lesions.
In young adults with acute pancreatitis a wide etiologic spectrum has to be considered. Among the possible causes, cystic fibrosis is rare. Besides the typical clinical triad of pancreatic exocrine insufficiency, chronic obstructive pulmonary disease, and elevated sweat chloride levels, there is a wide spectrum of variants of the cystic fibrosis syndrome. Especially mild manifestations of the disease may, therefore, escape proper identification. Here we describe a young man who presented initially with recurrent acute pancreatitis without pulmonary disease and without a family history of cystic fibrosis, in whom the diagnosis of cystic fibrosis was established by slightly elevated sweat chloride levels and obstructive azoospermia. Five years after the first attack of pancreatitis the patient developed pancreatic exocrine insufficiency.
A positional cloning effort in French Canadian families with Paget's disease of bone (PDB) resulted in the identification of a mutation in the sequestosome1 (SQSTM1) gene in a subset of both familial and sporadic PDB cases. This was confirmed in samples of mainly United Kingdom (UK) origin. In this study, we performed both mutation analysis and association studies in order to evaluate the role of this gene in a collection of isolated Belgian PDB patients. A mutation in the SQSTM1 gene was found in only 6 of 111 patients (5.4%). In all cases it involves the P392L mutation, previously shown to be common in both familial and sporadic cases. To perform association studies, we selected 8 single nucleotide polymorphisms (SNPs) and looked for linkage disequilibrium (LD) between these. Haplotype analysis indicated that typing of 3 Tag SNPs (IVS1 + 633A/C, IVS5 - 23A/G, and 976A/G) enables us to identify the most common haplotypes. Association studies for the 3 selected SNPs, based on 105 PDB cases without a SQSTM1 mutation and 159 control individuals, did not support a possible influence of natural variants in the SQSTM1 gene either on the pathogenesis of PDB or on the disease severity. In conclusion, our study confirms that the P392L mutation is a recurrent mutation causing PDB in different populations. We were not able to show an association between SQSTM1 polymorphisms and PDB in our population but this clearly needs to be extended to other populations. The presented identification of haplotype Tag SNPs will be of major help for such studies.
Aortic atherosclerosis has early been recognized as a potential source of embolism. The histological finding of cholesterol clefts in small end-arteries characterized the entity of cholesterol embolism. The clinical picture was extremely variable and the diagnosis was frequently established post-mortem or by means of invasive although insensitive procedures including biopsy and angiography. Therefore, cholesterol embolism was thought to be rare. With the routine use of transesophageal echocardiography for the diagnostic workup of arterial embolism, aortic atherosclerosis was shown to be the source of otherwise unexplainable embolism. Cross-sectional studies demonstrated an independent association between prominent plaques of more than 4 to 5 mm of thickness or plaques with mobile components in the aortic arch. In follow-up studies, the risk of embolic events in patients with this kind of lesions exceeded 10% per patient-year. The results of pathological studies were consistent with these findings showing that ulcerated complex plaques carry an independent risk for embolic events. Apart from spontaneous embolism, atherosclerosis of the proximal aorta was shown to be a cause of embolic complications during cardiac surgery and catheterization procedures which involve the aorta. Medical treatment for the prevention of embolism in atherosclerotic disease of the aorta has not been studied systematically. In a variant form of aortic atherosclerosis consisting of mobile pedunculated thrombi inserting on relatively small plaques, anticoagulant therapy has proved to be useful in small numbers of patients. Recurrent embolic events could be prevented and regression of the thrombotic masses has been observed.
The odontogenic fibroma is a benign neoplasm infrequently reported in the literature (20 cases). Nineteen additional examples are reported. This lesion occurs most frequently in the maxilla anterior to the molars and displays a striking female predilection. On occasion, it may be associated with an unerupted mandibular third molar. Histomorphologically, it is not encapsulated. A spectrum of fibrous connective tissue stroma is present: from myxoid to densely hyalinized and from relatively acellular to cellular. Calcification may or may not be present. It is distinguished by the presence of sparse cords and islands of inactive odontogenic epithelium. Enucleation or surgical curettage is appropriate therapy and recurrence is low. As there appears to be no correlation of histologic pattern with clinical behavior, it seems unnecessary to try to separate the tumor into two variants.
BACKGROUND: Myxoid leiomyosarcoma (MLMS) of the vulva is a mesenchymal tumor with only five reported cases in the literature. CASE: We report an 85-year-old woman with a unilateral nonulcerating, painless vulvar mass. According to the patient, the mass slowly enlarged. Initial biopsies were benign. However, clinically, this lesion was suspicious for a soft tissue tumor. Therefore, the mass was removed by a wide local excision. Definitive histology revealed a myxoid leiomyosarcoma of the vulva. At present, 25 months after the operation, the patient is well with no sign of recurrence. CONCLUSIONS: Vulvar myxoid leiomyosarcomas are rare and can be confused with other benign or malignant tumors. It is important to be aware of this rare tumor variant, in order to plan appropriate treatment.
PURPOSE: Partial cystectomy is a surgical option for select patients diagnosed with urothelial carcinoma. We review our experience with partial cystectomy for muscle invasive urothelial carcinoma to assess local control and survival rates. MATERIAL AND METHODS: From 1982 to 2003 a total of 37 patients with muscle invasive urothelial carcinoma underwent partial cystectomy with curative intent. Reviewed data included history of superficial tumors, presence of variant histology, tumor location, clinical stage, pathological stage, presence of carcinoma in situ, adjuvant therapy and disease status. RESULTS: The 5-year overall, disease specific and recurrence-free survival rates were 67%, 87% and 39%, respectively. Mean followup was 72.6 months (range 6 to 217). Of the 37 patients 19 (51%) did not have tumor recurrence, 9 (24%) had superficial recurrence in the bladder that was treated successfully and 9 (24%) had recurrence with advanced disease. A total of 24 patients (65%) had an intact bladder with no evidence of disease after a median of 53 months. There were 6 patients (16%) who died of bladder cancer, 3 of whom died of late recurrence of muscle invasive cancer (41, 44 and 138 months after partial cystectomy). On multivariate analysis higher pathological stage (HR 3.4, p = 0.04) was associated with shorter recurrence-free survival. A history of superficial tumors (p <0.01) and clinical stage (p = 0.01) was associated with advanced recurrence-free survival. The use of adjuvant chemotherapy (HR 0.18, p = 0.03) was associated with prolonged advanced recurrence-free survival, however adjuvant chemotherapy did not impact overall survival. CONCLUSIONS: Partial cystectomy provides adequate local control of muscle invasive bladder cancer in select patients. Because late recurrence is not uncommon and is potentially life threatening, lifelong followup with cystoscopy is recommended.
Meigs' syndrome is defined as a hydrothorax with ascites and a pelvic tumor, both of which resolve on removal of the tumor. Pseudo-Meigs' is a variant not possessing the original tumor cell types described by Meigs. Both these syndromes should be considered in otherwise healthy women who present with either new or recurrent hydrothorax and ascites. This case concerns a 21-year-old woman who presented to the emergency department (ED) with a recurrent hydrothorax. After performing a pelvic examination that was suspicious for a pelvic mass, further evaluation by ultrasonography showed ascites and a pelvic tumor. Surgeons from the Obstetrics and Gynecology Department performed an exploratory laparotomy with removal of the tumor. Subsequently, there was no recurrence of the ascites and hydrothorax. The tumor was diagnosed histologically as a benign mature teratoma. The literature of Meigs' and Pseudo-Meigs' is reviewed, focusing on the history, pathology, and clinical characteristics. The clinical significance for the emergency physician is discussed.
We present a case of the aggressive variant of African endemic Kaposi's Sarcoma (AKS) which presented as a large fungating and ulcerated plantar mass. Our patient responded extremely well to chemotherapy with no recurrence for 9 months after treatment completion. AKS is one of the most common cutaneous neoplasms in black Africans and although rare in Europe, it may be seen more frequently in the future because of the ease of international travel. The existing classification of KS into five different types (classic, African-endemic, iatrogenically immunocompromised patients, epidemic HIV-related and Mediterranean-endemic) cannot address fully the many anomalies described in the disease. The detection of a new herpes simplex-like viral DNA sequence (HHV-8) in different types of KS helps to explain some of the enigma described in this disease.
Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34. More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was approximately 30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis. This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.
BACKGROUND: Rearrangements of the bcl-2 gene (also known as BCL2) have been detected in up to 40% of cases of Hodgkin's disease, and it has been speculated that such rearrangements may have a role in the pathogenesis of Hodgkin's disease. PURPOSE: The purposes of this study were (a) to assess the frequency of clonal chromosomal abnormalities in Hodgkin's disease, (b) to identify recurrent changes, (c) to determine whether the bcl-2 gene rearrangement was present in Reed-Sternberg cells (the neoplastic cells of Hodgkin's disease) and their variants, and (d) to analyze whether the presence of t(14;18) translocations in Reed-Sternberg cells explains the observed bcl-2 gene rearrangements in Hodgkin's disease. METHODS: A cytogenetic study was performed on biopsy specimens from 28 consecutive untreated patients with Hodgkin's disease. The same patients were analyzed for bcl-2 gene rearrangement by a polymerase chain reaction (PCR) technique. To ascertain whether the abnormal karyotypes were present in and restricted to Reed-Sternberg cells, we also performed in situ hybridization with chromosome-specific probes. RESULTS: Abnormal metaphases were identified in 23 of the 28 patients. In 11 patients, the chromosome 14q region was abnormal; in six of these patients, there was involvement of the 14q32 region that comprises the gene encoding for heavy-chain immunoglobulin. Only one patient had a t(14;18) translocation, whereas almost 40% of these 28 patients showed bcl-2 gene rearrangements by a PCR method. The in situ hybridization method showed that the abnormal karyotype was present in and restricted to Reed-Sternberg cells. CONCLUSIONS: We conclude that the majority of cases of Hodgkin's disease contain a clonal population with an abnormal karyotype, comprising the Reed-Sternberg cells. The q32 region of chromosome 14 is frequently involved, but a t(14;18) translocation is extremely infrequent. The occurrence of a bcl-2 gene rearrangement in Hodgkin's disease most likely results from the presence of sporadic, small bystander B lymphocytes that carry the translocation and that also can be frequently detected in reactive lymphoid tissue such as tonsils. Also, a range of different chromosomal translocations may provide growth or survival advantages to Reed-Sternberg cells.