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[Genetic variants of acid erythrocytic phosphatase as a risk factor of rheumatic fever].

A study was made of the genetic variants (isoenzymes, phenotypes) of acid erythrocytic phosphatase (AcP) in 120 patients with rheumatic fever. There were 78 women and 42 men aged 16 to 57 years. The population data concerned with distribution of the AcP variants among the population of Moscow were used as control. As compared with control, the patients suffering from rheumatic fever demonstrated the accumulation of the rarely occurring variants of AcP (AC, BC and CC, in particular). A significant direct correlation was established between the activity of isoenzymes and relative risk of rheumatic fever incidence. The definite regularities in the distribution of AcP variants were found to depend on the disease clinical patterns (the articular syndrome, the times of the formation of heart diseases, the character of recurrent rheumocarditis). The data obtained can used for distinguishing the rheumatic fever risk groups and forecasting the rheumatic process (to a certain degree of probability).

Acid Phosphatase↗

Hyperplasia of thymic gland.

Hyperplasia of the thymus is the most common anterior mediastinal mass in infants. It is however exceedingly difficult to evaluate by the weight of the gland as it continues to grow after birth until puberty and thereafter undergoes progressive atrophy. It normally maintains most of the radiographic characteristics of the normal thymus. Massive thymic hyperplasia, a rare variant of true thymic hyperplasia is extremely rare during the first two decades of life and clinically can cause mediastinal compression or acute and recurrent pulmonary infection. Two such cases are reported and the clinico-pathology is briefly described and discussed.

Diagnosis, Differential↗

Microsurgical anatomy of the anterior cerebral-anterior communicating-recurrent artery complex.

The microvascular relationships important to surgery of aneurysms in the anterior communicating region were defined in 50 cadaver brains. The recurrent artery of Heubner was frequently exposed before the A-1 segment in defining the neck on anterior cerebral aneurysms because it commonly courses anterior to A-1. It arose from the A-2 segment of the anterior cerebral artery (ACA) in 78% and most commonly terminated in the area of the anterior perforated substance, and lateral to it in the Sylvian fissure. The anterior communicating artery (ACoA) frequently gave rise to perforating arteries which terminated in the superior surface of the optic chiasm and above the chiasm in the anterior hypothalamus. This finding contrasts with previous reports that no perforating branches arise from the communicating artery. The proximal half of the A=1 segment was a richer source of perforating arteries than the distal half. The A-1 branches most commonly terminated in the anterior perforated substance, the optic chiasm, and the region of the optic tract. The ACoA increased in size as the difference in the diameter between the right and left A-1 segments increased. Frequent variants such as double or triple ACoA's, triple A-2 segments, and duplication of the A-1 segments were encountered. The clinical consequences of occlusion of the recurrent artery and of the perforators from the ACoA and medial and lateral segment of A-1 are reviewed.

Arteries↗

Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis.

OBJECTIVES: Defects of PRSS1, SPINK1, CFTR and AAT are considered causative or predisposing to pancreatitis. The aim of this study was to evaluate the impact of these defects into molecular pathology of chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). METHODS: Ninety-two children with CP or ARP, 55 family members and 50 controls were investigated. The subjects were screened for PRSS1 mutations: R122H, R122C, A16V, N29I; SPINK1 N34S variant; panel of 14 CFTR defects: INNOLiPA CFTR12, CFTRdele2,3 and IVS8-T variant or panel of 3 CFTR defects-F508del, CFTRdele2,3 and IVS8-T; AAT mutations: E264V, E342K. RESULTS: We identified 1 mutated allele in at least 1 of 4 genes in 31 of 92 patients and 12 of 50 controls (P = 0.157). Mutations in SPINK1 and PRSS1 were most frequent. PRSS1 mutations were identified mainly in CP patients (9.6% of CP vs 2.5% of ARP alleles, P = 0.094), whereas N34S SPINK1 mutation was present with comparable frequency in CP and ARP patients (7.7% vs 10.0%, P = 0.768). The frequency of mutations in CFTR alleles was similar to controls (4.9% vs 5%, P = 0.587). Overall frequency of AAT mutations was lower than in the controls. Family studies showed that defects in the examined genes did not always segregate with disease. CONCLUSIONS: PRSS1 defects seem to be causative for pancreatitis, whereas defects in SPINK1 are suggested to be associated with the disease. No association between CFTR mutations and pancreatitis was observed. The importance of AAT variants remains speculative.

Acute Disease↗

Pyruvate kinase deficiency and leg ulcers.

We report a family with a new pyruvate kinase (PK) variant in which leg ulcers have been present in four of the five affected homozygous family members, but not in any of the unaffected individuals. The propositus, an 18-yr-old boy, suffered from recurrent crises of hemolytic anemia and leg ulcers. A splenectomy was performed and the leg ulcer was treated un-successfully with a pinch graft. Studies ondialyzed hemolysates showed that the enzyme was kinetically abnorma, being almost entirely resistant to activation by fructose diphosphate. THE THERMOSTABILITY OF THE ENZYME WAS MODERATELY DECREASED, AND THE ELECTROPHORETIC MOBILITY WAS NORMAL. One may speculate that the development of leg ulcers in some kinships with PK deficiency may be related to variants of PK which exert unusual effects on the rheologic properties of the red cell in vivo.

Adolescent↗

Atypical fibroxanthoma: a clinicopathological study of 89 cases.

Atypical fibroxanthoma is a controversial entity with a disputed histogenesis. It has recently been suggested that most atypical fibroxanthoma are actually variants of squamous cell carcinoma. We reviewed 100 purported cases of atypical fibroxanthoma received over 4 years to perform clinical follow up and immunohistochemical markers. In particular, we focused on the detection of any recurrence or metastasis. Ten cases were subsequently excluded on the basis of either incorrect coding, or insufficient or absent paraffin blocks on file. A further case was interpreted as a malignant fibrous histiocytoma. Additional new markers, such as CD10 and CD99, were employed in a proportion of cases. Our cases were typical of the usual clinical presentation of atypical fibroxanthoma on the skin of the sun-damaged elderly. We found no cases of recurrent or metastatic atypical fibroxanthoma. Two patients developed a second primary atypical fibroxanthoma. CD10 proved to be a useful marker for atypical fibroxanthoma when used on 20 cases in the present study, as was CD99 in seven cases. The only case demonstrating positive staining for keratin also stained for CD10. It had dual features of atypical fibroxanthoma and squamous cell carcinoma. However, as the majority of atypical fibroxanthoma had no adjacent solar keratosis, our data suggest it is unlikely that atypical fibroxanthoma is a variant of squamous cell carcinoma.

Adult↗

Fibrohistiocytic lipoma: twelve cases of a previously undescribed benign fatty tumor.

A lipoma with a spindled proliferation within it, resembling known (myo)fibroblastic lesions such as fibrous histiocytoma or dermatofibrosarcoma protuberans, (ie, fibrohistiocytic lipoma), has not been previously reported. This tumor varies from other classic lipoma variants, including spindle cell lipoma, myolipoma, angiolipoma, and fibrolipoma. We examine the clinicopathologic findings of this new lipoma variant. The Soft Tissue Pathology Registry of the Armed Forces Institute of Pathology was searched for patients with "lipoma with fibrohistiocytic proliferation." Lesions that were better classified as other entities were excluded. Patient slides and clinical history, including associated lesions, family history, duration of symptoms, history of trauma, natural progression, and treatments, were reviewed. Immunohistochemistry was performed on cases with available material (n = 6). Twelve patients with fibrohistiocytic lipoma were included. All tumors revealed a well-distributed quilt-like proliferation or solid focus of slightly plump to relatively bland spindled cells with collagenous stroma in short fascicular and storiform growth patterns. These spindled cells resembled those seen in either fibrous histiocytoma or dermatofibrosarcoma protuberans. However, the spindled proliferation was all within a well-circumscribed lipoma. The lesions lack the dermal involvement or plump pleomorphism of fibrous histiocytoma and the dermal involvement or infiltrative growth pattern of dermatofibrosarcoma protuberans. The fatty component demonstrated heterogeneously sized adipocytes, as those seen in other lipomas. Inflammation and hemosiderin were minimal. Mast cells were not identified. The tumors were typically found in the subcutis of the trunk of men (10 of 12; one each on the wrist and leg; mean age, 31 years). The average size of the lesions was 3.0 cm, and they were present for a mean duration of 10 months prior to surgical excision. One patient had two concurrent lesions; all others had solitary tumors. Another patient had a intracranial dermoid cyst removed during childhood. Four patients had a personal or family history of hypercholesterolemia, hypertension, or myocardial infarction. There was no history of antecedent trauma. Cases studied were positive for vimentin, calponin (5 of 5), CD34 (3 of 5), and occasionally KP-1 or lysozyme in the spindled component, and all cases studied were negative for the actins, caldesmon, S-100 protein, desmin, cytokeratins, and epithelial membrane antigen. Although the actins were negative in our laboratory, the more sensitive calponin positivity suggests myofibroblastic phenotype of the spindled component of this lesion. CD34-positive fibroblasts were present in three of five cases. Of eight patients with follow-up, there were no recurrences; all patients were alive and free of disease over a mean of 10 years (range, 2 months to 31 years). We have identified a lipoma variant, fibrohistiocytic lipoma, that has not been previously described. In our experience the morphology and calponin positivity suggest myofibroblastic phenotype for the spindled cells, within a lipoma. This entity can be distinguished from fibrous histiocytoma, fibromatosis, dermatofibrosarcoma protuberans, spindle cell lipoma and other lipoma, and liposarcoma variants.

Adult↗

[Time perception by patients with depression in manic-depressive psychosis and recurrent schizophrenia].

The author provides the results of a clinicopsychological examination of time perception and surviving by 58 depressive patients with manic-depressive psychosis (MDP) and attack-like schizophrenia. The time surviving and counting off were done in the three clinical variants of depression: hypochondriacal, agitated and apathetic. The surviving of time violation was regarded in the structure of depersonalization disorders, particularly "Ego" stability in time as well as bearing in mind the duration, sequence, localization, rate, tempo and rhythm of the events and emotional experience. The most pronounced and diverse disorders of time surviving were recorded in hypochondriacal depression of MDP, less remarkable and latent in apathetic depression within the framework of schizophrenia.

Adult↗

Median nerve compression by a radially inserted palmaris longus tendon after release of the antebrachial fascia: A complication of carpal tunnel release.

We describe a case that had recurrent median nerve compression after release of the antebrachial fascia in carpal tunnel release. The nerve was compressed by a palmaris longus tendon that was inserted radially into the thenar fascia. After decompression (detachment of the tendon) the patient had symptom relief. Release of the antebrachial fascia in the presence of this tendon variant carries a risk of median nerve compression by the tendon.

Carpal Tunnel Syndrome↗

Multiple recurrent and de novo odontogenic keratocysts associated with oral-facial-digital syndrome.

In 1954, Papillon-Leage and Psaume were the first to describe the clinical characteristics of oral-facial-digital syndrome (OFDS). On the basis of their clinical features and the inheritance pattern, 2 variants were initially distinguished, namely OFDS type I (Papillon-Leage and Psaume) and OFDS type II, or Mohr syndrome. At present, 11 types of OFDS have been discovered. OFDS represents a heterogeneous group of disorders characterized by oral manifestations including oral frenula, cleft or lobulated tongue, high arched palate, cleft lip and/or palate, facial anomalies, and digital abnormalities such as syndactyly, polydactyly, brachydactyly, and clinodactyly. Depending on the type of OFDS, abnormalities may be present in other organs, such as the brain and heart. We report a patient with OFDS in whom multiple recurrent and de novo keratocysts were found. Although multiple keratocysts are commonly found in Gorlin-Goltz nevoid basal cell carcinoma syndrome, a relationship between OFDS and multiple keratocysts has not been described.

Child↗

A t(17;20)(q21;q12) masking a variant t(15;17)(q22;q21) in a patient with acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is genetically characterized by a reciprocal translocation between chromosomes 15 and 17, the t(15;17)(q22;q21), which results in the fusion gene PML/RARA. A small proportion of patients with APL have complex or simple variants of this translocation. We report the case of a 31-year-old woman with APL (FAB-M3 classical form) carrying an apparently balanced translocation t(17;20)(q21;q12) masking a t(15;17)(q22;q21) confirmed by fluorescence in situ hybridization (FISH) and molecular studies. The patient was treated with an all-trans-retinoic acid (ATRA) plus anthracycline-based protocol and achieved complete remission, with no recurrence to date. These results illustrate the usefulness of combining cytogenetics, FISH, and reverse transcription-polymerase chain reaction (RT-PCR) methods to evidence the PML/RARA fusion gene in cases with morphologic suspicion of APL with variant or cryptic t(15;17).

Adult↗

Lipomatous hemangiopericytoma: a fat-containing variant of solitary fibrous tumor? Clinicopathologic, immunohistochemical, and ultrastructural analysis of a series in favor of a unifying concept.

The dinicopathologic, immunohistochemical and ultrastructural features of 13 lipomatous hemangiopericytomas are presented. There were 6 male and 7 female patients whose ages at diagnosis ranged from 27 to 75 years (median 48) all presenting with a mass of variable duration. The tumor sizes ranged from 1.7 cm to 19 cm (median 5.5 cm). The locations included the orbit (1), neck (1), mediastinum (1), epicardium (1), retroperitoneum (3), right iliac fossa (1), and upper (1) and lower (4) extremity. Histologically, the lesions were composed of a varying admixture of spindle-shaped to round cells, variably collagenous stroma, adipose tissue, and branched, often thick-walled, hemangiopericytoma-like vessels. For 11 tumors, the mitotic activity ranged from 1 to 3 mitoses per 10 high-power fields (HPF). One tumor which contained hypercellular areas showed 13 mitoses per 10 HPF, and another hypercellular lesion showed up to 43 mitoses per 10 HPF, abnormal mitoses, and necrosis. Immunohistochemically, tumor cells were invariably positive for vimentin and CD99, and mostly for CD34 but negative for desmin, keratin, CD31, CD117 (c-kit), and inhibin. About half of the tumors showed reactivity for bcl-2. Occasionally, focal reactivity was also observed for smooth muscle actin, muscle-specific actin, S100 protein, and epithelial membrane antigen. Ultrastructural examination of seven cases showed features in keeping with fibroblastic, myofibroblastic, or pericytic differentiation. Treatment consisted of simple tumorectomy in 10 cases and wide excision in 3. Follow-up information on 10 patients (range: 6 to 77 months; median: 18 months) showed no recurrence. Lipomatous hemangiopericytoma which share the clinical, pathologic, immunohistochemical, and ultrastructural features of solitary fibrous tumor (SFT) is likely to represent, in most cases, a fat-containing variant of SFT.

Actin Cytoskeleton↗

Variant lymphoproliferative disorder of granular lymphocytes (LDGL) following Hodgkin lymphoma.

A 41-year-old Caucasian female was diagnosed with a CD3(+) CD4(+) CD8(+) variant of lymphoproliferative disorder of granular lymphocytes (LDGL) in the third year of remission following treatment of stage III-B Hodgkin lymphoma (HL). The patient was asymptomatic at diagnosis, without clinical evidence of immune disorder or recurrence of HL. Diagnosis was made incidentally, secondary to lymphocytosis discovered on a routine follow-up post HL therapy. Clonal chromosomal abnormalities were seen in 20% of peripheral blood lymphocytes with a karyotype 46, XX, t(2;6;2;11) (p13;q23;q24;q23). The breakpoint on 11q23 is distal to the MLL gene as shown by fluorescence in situ hybridization (FISH) analysis. To our knowledge, this is the first report of variant LDGL in association with HL treatment with documented clonal chromosomal abnormalities.

Adult↗

Recurrent tachycardia after selective ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia.

Recurrence rate of atrioventricular (AV) nodal reentrant tachycardia after successful radiofrequency ablation varies widely, and the determinants of recurrent AV nodal reentrant tachycardia remain controversial. Furthermore, true or pseudorecurrence of tachycardia after successful ablation in patients with different forms of AV nodal reentrant tachycardia has not been evaluated systematically. Three hundred sixty-two patients (161 men and 201 women [mean age 52 +/- 16 years]), including 314 patients with typical-form, 10 patients with atypical-form, 4 patients with variant-form, and 34 patients with multiple-form AV nodal reentrant tachycardias, received selective radiofrequency ablation of the anterograde and/or retrograde slow AV nodal pathway. During a mean follow-up of 27 +/- 11 months, 9 patients (2.5%) experienced recurrent AV nodal reentrant tachycardia (true recurrence, group A), and 8 (2.2%) had inappropriate sinus tachycardia or paroxysmal atrial tachyarrhythmias (pseudorecurrence, group B). Neither the true nor pseudorecurrence rate was different among the 4 different forms of tachycardia. Factors including presence of residual slow pathway conduction, a single AV nodal reentrant echo beat, absence of an accelerated junctional rhythm during successful ablation, facilitating induction of tachycardia by isoproterenol, radiofrequency pulse number, and successful ablation site were not associated with an increased risk of recurrent AV nodal reentrant tachycardia. The onset time of recurrent tachycardia was significantly late in group B patients (30 +/- 21 vs 292 +/- 240 days, p = 0.04). Thus, this study demonstrated that both true and pseudorecurrence could occur after successful ablation.

Adolescent↗

Squamous cell carcinoma of the conjunctiva: clinicopathological features in 287 cases.

BACKGROUND: Squamous cell carcinoma is the most frequently encountered malignant tumour of the conjunctiva. The objective of this study was to describe the clinicopathological features of patients with squamous cell carcinoma of the conjunctiva seen at a large ophthalmologic hospital in Mexico City. METHODS: We reviewed the clinical and pathological files of all patients with documented squamous cell carcinoma of the conjunctiva seen at the hospital between 1957 and 1996. RESULTS: A total of 287 cases (286 patients) were reviewed. The mean age of the patients was 60.4 (range 12 to 99) years; 55% were male. The clinical diagnosis was accurate in 41% of cases. Typical keratinized squamous cell carcinoma of the conjunctiva accounted for 98% of the lesions, and there were small numbers of histologic variants: lymphoepithelioma-like carcinoma (three cases), spindle cell carcinoma (two cases) and mucoepidermoid carcinoma (one case). Evidence of local extension of the tumour was found in 150 patients (52%), with the cornea being most frequently involved (108 cases [38%]). Regional metastasis was found in two patients, to a submandibular lymph node in one and to a preauricular lymph node in the other. The most common form of treatment was local resection (258 cases [90%]). The mean length of follow-up was 7.7 (range 2 to 24) months. The recurrence rate was 5.2%. INTERPRETATION: We report a large series of patients with squamous cell carcinoma of the conjunctiva. The incidence of local extension was high. Three cases of lymphoepithelioma-like carcinoma, a variant not previously reported in the conjunctiva, were encountered and were confirmed by immunohistochemical reactions.

Adolescent↗

Epithelioid sarcoma in children and adolescents: a report from the Italian Soft Tissue Sarcoma Committee.

BACKGROUND: Epithelioid sarcoma (ES) is an uncommon malignant soft tissue tumor. To the authors' knowledge, little information is available to date concerning its clinical features and management in children and adolescents, particularly with regard to the recently described proximal-type variant. The current study concerns 30 patients age<18 years who were enrolled in the Italian Soft Tissue Sarcoma Committee protocols. METHODS: Histopathologic specimens, clinical data, and treatment modalities were reviewed for the current analysis. Nineteen patients had classic ES and 11 had proximal-type ES. Surgery was the mainstay of treatment; radiotherapy was given to six patients considered to be at risk of local disease recurrence due to incomplete resection, and chemotherapy was administered to eight patients. RESULTS: With a median follow-up of 66 months, the 5-year event-free survival (EFS) and overall survival (OS) rates were 61.7% and 92.4%, respectively, but the OS rate dropped to 86.9% and 72.4%, respectively, at 10 years and 15 years. Local disease recurrence was the major cause of treatment failure. The most significant finding influencing both EFS and OS was tumor site, with a tumor location in the extremities predicting a favorable outcome. Initially unfavorable clinical findings and a worse outcome were associated with the proximal-type variant of ES. A response to chemotherapy was noted in three of the seven patients with measurable disease. CONCLUSIONS: The current study confirms some typical features of ES (i.e., the peculiar superficial distal location [i.e., the hand, fingers], indolent growth, and a tendency to recur locally). The current study data do not clearly confirm the strong tendency for the lymph node involvement described in adult ES patients. Further studies are needed to better define the clinical behavior and biology of the proximal-type variant of ES.

Adolescent↗