Basal or stimulated thyroglobulin in evaluating response to treatment in papillary thyroid carcinoma? A retrospective cohort study.

OBJECTIVE: It is not clear whether response to initial treatment in papillary thyroid carcinoma (PTC) patients is best evaluated by measuring thyroglobulin (Tg) in the presence of levothyroxine (BTg) or when stimulated by elevated TSH (STg). The aim of this study was to evaluate whether response to therapy 1 year after initial treatment changes with the use of STg in relation to BTg in PTC patients treated with total thyroidectomy (TT) and radioiodine (131I), and, if observed, to assess which response is better associated with clinical course. SUBJECTS AND METHODS: This is a retrospective study of 148 PTC patients submitted to TT and 131I. We analyzed the response to therapy (excellent, biochemical incomplete, or indeterminate) at 1 year after initial treatment, using BTg or STg, and compared which method was better associated with "excellent response at final evaluation." RESULTS: Twenty-eight patients (20.4%) presented change in response to therapy, with 17 of these (60.7%) presenting a worse response. Response using STg was 1.6 times better associated with proposed outcome [odds ratio (OR) = 4.61; confidence interval 95% (IC95%): 2.13-9.98] than with BTg (OR = 2.84; IC95%: 1.33-6.06). CONCLUSION: Response to therapy at 1 year using STg was altered in approximately 20% of cases and therefore proved to be a better predictor of excellent response in the last evaluation.

Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study

ABSTRACT Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusions: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement.

Postoperative serum magnesium levels as a predictor for the need for calcium replacement after total thyroidectomy: a prospective study.

Objective: Our aim was to assess the ability of serum magnesium (Mg), measured on the first postoperative day (Mg1PO), to predict the need for calcium (Ca) replacement in patients undergoing total thyroidectomy (TT). Subjects and methods: Eighty patients undergoing TT, with Mg1PO and PTH dosage in the first (PTH1h) and eighth (PTH8h) hours after TT, were evaluated for the need for Ca replacement. Data were evaluated by uni/multivariate logistic regression and Receiver Operating Characteristic (ROC) curve. Results: 32 patients (40%) required Ca replacement. Median PTH1h, PTH8h and Mg1PO were higher in the no replacement group: 17 versus (vs) 3 pg/mL (p < 0.001), 18.2 vs 3.0 pg/mL (p < 0.001) and 2 vs 1.6 mg/dL (p < 0.001), respectively. Mg1PO was the isolated predictor for this replacement (odds ratio = 0.0004, 95% confidence interval: 0.000003-0.04; p = 0.001), with the cut-off value of 1.8 mg/dL showing sensitivity and specificity of 78.1% and 87.5%, respectively. Conclusion: In this group of patients, serum Mg1PO was the isolated predictor for the need for Ca replacement.

The role of immunohistochemistry in the assessment of classical Hodgkin lymphoma microenvironment.

INTRODUCTION: Classical Hodgkin lymphoma (CHL) has a unique cellular composition, containing a minority of neoplastic cells - Hodgkin and Reed-Sternberg (HRS) cells - in an inflammatory background. Investigations into this microenvironment have been given special importance in scientific hematopathology, playing an important role in elucidating its composition and its relationship to the prognosis of patients. OBJECTIVE: To investigate microenvironment tumor markers in CHL, in order to analyze their interactions with clinical-morphological aspects of interest in onco-hematopathology. METHODS: This retrospective study analyzed 184 patients with a pathologic diagnosis of CHL. Clinical data were reviewed from medical records. A morphological and immunophenotypic study with CD20, CD30, CD15, PAX-5, CD3, CD4, CD8, CD68, CD34, CD138 and PD-1 were performed. The data were tabulated and p value less than 0.05 was considered significant. RESULTS: The time-to-cure was shorter in CD20+ patients, especially in those with more than 25% positivity (P=0.0183). The time-to-cure (P=0.0309) and the death (P=0.016) rates were shorter in PD-1 negative patients. Among patients with the presence of plasma cells in the microenvironment, those with lower numbers tend to be cured earlier (P=0.0374). Higher vascular density is associated with lower frequency of B symptoms (P=0.036) and presence of disease recurrence (P=0.004). CONCLUSIONS: The microenvironment is certainly the setting of increasingly robust studies and the findings of this work highlight non-neoplastic B lymphocytes, plasma cells, PD-1 lymphocytes, and vascular density, related to prognosis of CHL patients.

Patients with Classical Hodgkin Lymphoma with Less Than 10.5 CD20-Positive Reed-Sternberg Cells in 10 High-Power Fields Have Better Prognosis.

The CD20 immunoexpression in classical Hodgkin lymphoma (CHL) is variable and it may represent an intersection between the pathophysiology of CHL and the clinical prognosis of patients. Retrospective study with 174 patients with pathological diagnosis of CHL. Clinical data were reviewed from medical records. Immunophenotypic study with CD20 were performed in two ways: hotspot count and in 10 high-power fields (HPF). The data were tabulated and the p value less than 0.05 was considered significant. The CD20-positive phenotype was found in 45 (25.9%) of the total of 174 patients with available material. Patients with CD20 positivity on neoplastic cells tend to heal earlier, particularly those with less than 10.5 cells/10 HPF (p = 0.037). Patients with CHL with less than 10.5 CD20-positive Reed-Sternberg cells in 10 HPF have better prognosis.

Mucosa-associated lymphoid tissue lymphoma in the terminal ileum: A case report.

BACKGROUND: The lymphoma of the mucosa-associated lymphoid tissue (MALT) is predominantly found in the stomach. The few cases reported in the literature of MALT lymphomas affecting the ileum are in patients who are already symptomatic and with clear advanced endoscopic findings. We present the first case of an asymptomatic female patient who underwent colonoscopy as a routine examination with the findings of an ulcer in the distal ileum region, which histopathological examination and associated immunohistochemistry revealed the diagnosis of MALT lymphoma. CASE SUMMARY: A 57-year-old asymptomatic female patient underwent a colonoscopy exam for screening. The examination revealed an ulcer of medium depth with well-defined borders covered by a thin layer of fibrin and a halo of hyperemia in the distal ileum portion. Findings are nonspecific but may signal infections by viruses, protozoa, and parasites or inflammatory diseases such as Crohn's disease. Biopsies of the ulcer were taken. The anatomopathological result revealed an atypical diffuse lymphocytic infiltrate of small cells with a characteristic cytoplasmic halo of marginal zone cells. The immunohistochemical study was performed and the results demonstrated a negative neoplastic infiltrate for the expression of cyclin D1 and cytokeratin AE1/AE3 and a positive for BCL60 in the germinal center. The test also revealed CD10 positivity in the glandular epithelium and germinal center of a reactive follicle with dual-labeling of CD20 and CD3 demonstrating the B lymphocyte nature of the neoplastic infiltrate. In BCL2 protein labeling, the neoplastic infiltrate is strongly positive with a negative germinal center. The findings are consistent with immunophenotype B non-Hodgkin's lymphoma, better classified as extranodal MALT. The patient was treated with chemotherapy and showed complete regression of the disease, as evidenced by colonoscopy performed after treatment. CONCLUSION: MALT lymphomas in the terminal ileum are extremely rare and only 4 cases have been reported in the literature. Given the low sensitivity and specificity of endoscopic images in these cases, the pathology can be confused with other important differential diagnoses such as inflammatory diseases or infectious diseases and which makes the biopsy important, even in asymptomatic patients, paired with anatomopathological analysis and immunohistochemistry which is the gold standard for correct diagnosis.

Is there a relationship between preoperative cytological diagnosis and evolution in patients with differentiated thyroid carcinoma? A retrospective study.

Objective: Cytological analysis and Bethesda classification of thyroid nodules is the standard method of diagnosing differentiated thyroid carcinoma (DTC). However, even for nodules with a non-malignant cytological diagnosis, there is a not insignificant risk of cancer. There are doubts whether this lack of certainty would influence patient prognosis. Our aim was to compare patients with DTC, classified according to the preoperative cytological diagnosis, regarding their evolution. Methods: A retrospective study was carried out with 108 DTC patients submitted to total thyroidectomy (TT) between 2009 and 2015, divided into three groups according to preoperative cytological diagnosis (Bethesda classification): classes I/II, III/IV, and V/VI. Groups were compared for evolution considering response to treatment at last evaluation as well as time disease free. Statistical analysis used ANOVA, chi squared, and Kaplan-Meier curves with p<0.05 considered significant. Results: Groups differed for time between nodule puncture and TT [in months; V/VI (2.35 ± 2.48) < III/IV (7.32 ± 6.34) < I/II (13.36 ± 8.9); p < 0.0001]. There was no significant difference between groups for evolution at final evaluation (disease free status; classes I/II: 71.4%; classes III/IV: 60%; classes V/VI: 66.6%; p = 0.7433), as well as time disease free (in months; classes I/II: 34.57 ± 25.82; classes III/IV: 38.04 ± 26.66; classes V/VI: 30.84 ± 26.34; p = 0.3841). Conclusion: DTC patients classified according to preoperative cytological diagnosis did not differ for evolution. Although patients with non-malignant cytological diagnoses were submitted to TT later, this did not affect the evolution of the cases.

Is there a relationship between preoperative cytological diagnosis and evolution in patients with differentiated thyroid carcinoma? A retrospective study

ABSTRACT Objective: Cytological analysis and Bethesda classification of thyroid nodules is the standard method of diagnosing differentiated thyroid carcinoma (DTC). However, even for nodules with a non-malignant cytological diagnosis, there is a not insignificant risk of cancer. There are doubts whether this lack of certainty would influence patient prognosis. Our aim was to compare patients with DTC, classified according to the preoperative cytological diagnosis, regarding their evolution. Subjects and methods: A retrospective study was carried out with 108 DTC patients submitted to total thyroidectomy (TT) between 2009 and 2015, divided into three groups according to preoperative cytological diagnosis (Bethesda classification): classes I/II, III/IV, and V/VI. Groups were compared for evolution considering response to treatment at last evaluation as well as time disease free. Statistical analysis used ANOVA, chi squared, and Kaplan-Meier curves with p<0.05 considered significant. Results: Groups differed for time between nodule puncture and TT [in months; V/VI (2.35 ± 2.48) < III/IV (7.32 ± 6.34) < I/II (13.36 ± 8.9); p < 0.0001]. There was no significant difference between groups for evolution at final evaluation (disease free status; classes I/II: 71.4%; classes III/IV: 60%; classes V/VI: 66.6%; p = 0.7433), as well as time disease free (in months; classes I/II: 34.57 ± 25.82; classes III/IV: 38.04 ± 26.66; classes V/VI: 30.84 ± 26.34; p = 0.3841). Conclusions: DTC patients classified according to preoperative cytological diagnosis did not differ for evolution. Although patients with non-malignant cytological diagnoses were submitted to TT later, this did not affect the evolution of the cases.

Thyroglobulin/thyrotropin ratio for predicting long-term response in differentiated thyroid carcinoma: a retrospective study

ABSTRACT Objective: Thyrotropin-stimulated thyroglobulin (STg) after total thyroidectomy is a prognosis marker for differentiated thyroid carcinoma (DTC). As Tg level is influenced by thyrotropin (TSH), perhaps the STg/TSH ratio is also a prognosis marker for these tumours. We aimed to compare STg/TSH ratio and first STg level in differentiated thyroid carcinoma patients for their ability to predict the long-term response to initial treatment. Subjects and methods: This retrospective study evaluated data from 181 DTC patients for first (1st) STg and STg/TSH ratio, at 1-3 months post-total thyroidectomy and before iodine-131 therapy, according to response to initial therapy [Excellent/Indeterminate or Incomplete (Biochemical/Structural)] observed at final evaluation, and with the survival time with excellent/indeterminate response. Results: Cases with incomplete response presented higher STg level [225.13 ± 585.26 ng/mL versus (vs) 20.4 ± 192.9 ng/mL; p < 0.001] and STg/TSH ratio (3.01 ± 7.8 vs 0.27 ± 2.58; p < 0.001). Cutoffs of 5 ng/mL for STg and 0.085 for STg/TSH displayed sensitivities of 76.7% and 76.9%, and specificities of 79.2% and 82.6%, respectively, in predicting response to therapy. Values below these cutoffs were associated with longer survival time in excellent/indeterminate response (140.4 vs 15.9 and 144.6 vs 15.9 months, respectively). Conclusion: STg/TSH ratio has a similar performance to the 1st STg in predicting long-term response to initial therapy.

Thyroglobulin/thyrotropin ratio for predicting long-term response in differentiated thyroid carcinoma: a retrospective study.

OBJECTIVE: Thyrotropin-stimulated thyroglobulin (STg) after total thyroidectomy is a prognosis marker for differentiated thyroid carcinoma (DTC). As Tg level is influenced by thyrotropin (TSH), perhaps the STg/TSH ratio is also a prognosis marker for these tumours. We aimed to compare STg/TSH ratio and first STg level in differentiated thyroid carcinoma patients for their ability to predict the long-term response to initial treatment. METHODS: This retrospective study evaluated data from 181 DTC patients for first (1st) STg and STg/TSH ratio, at 1-3 months post-total thyroidectomy and before iodine-131 therapy, according to response to initial therapy [Excellent/Indeterminate or Incomplete (Biochemical/Structural)] observed at final evaluation, and with the survival time with excellent/indeterminate response. RESULTS: Cases with incomplete response presented higher STg level [225.13 ± 585.26 ng/mL versus (vs) 20.4 ± 192.9 ng/mL; p < 0.001] and STg/TSH ratio (3.01 ± 7.8 vs 0.27 ± 2.58; p < 0.001). Cutoffs of 5 ng/mL for STg and 0.085 for STg/TSH displayed sensitivities of 76.7% and 76.9%, and specificities of 79.2% and 82.6%, respectively, in predicting response to therapy. Values below these cutoffs were associated with longer survival time in excellent/indeterminate response (140.4 vs 15.9 and 144.6 vs 15.9 months, respectively). CONCLUSION: STg/TSH ratio has a similar performance to the 1st STg in predicting long-term response to initial therapy.

Follicular Lesions with Papillary Nuclear Characteristics: Differences in Chromatin Detected by Computerized Image Analysis.

OBJECTIVE: Follicular lesions of the thyroid with papillary carcinoma nuclear characteristics are classified as infiltrative follicular variant of papillary thyroid carcinoma-FVPTC (IFVPTC), encapsulated/well demarcated FVPTC with tumour capsular invasion (IEFVPTC), and the newly described category "non-invasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) formerly known as non-invasive encapsulated FVPTC. This study evaluated whether computerized image analysis can detect nuclear differences between these three tumour subtypes. METHODS: Slides with histological material from 15 cases of NIFTP and 33 cases of FVPTC subtypes (22 IEFVPTC, and 11 IFVPTC) were analyzed using the Image J image processing program. Tumour cells were compared for both nuclear morphometry and chromatin textural characteristics. RESULTS: Nuclei from NIFTP and IFVPTC tumours differed in terms of chromatin textural features (grey intensity): mean (92.37 ± 21.01 vs 72.99 ± 14.73, p = 0.02), median (84.93 ± 21.17 vs 65.18 ± 17.08, p = 0.02), standard deviation (47.77 ± 9.55 vs 39.39 ± 7.18; p = 0.02), and coefficient of variation of standard deviation (19.96 ± 4.01 vs 24.75 ± 3.31; p = 0.003). No differences were found in relation to IEFVPTC. CONCLUSION: Computerized image analysis revealed differences in nuclear texture between NIFTP and IFVPTC, but not for IEFVPTC.

p53 and p21 expression in bone marrow clots of megaloblastic anemia patients.

The pathogenesis of megaloblastic hemopathies (MH) is centered on the deficiency of vitamin B12 and folic acid with interruption of erythrocyte maturation. This study researched the participation of p53 and p21 in the pathophysiology of the disease. A retrospective study enrolled 95 patients with histopathologic diagnosis by biopsy or bone marrow clot (BMB/BMC), with clinical review and immunohistochemical study in tissue microarray (TMA) for p53 and p21, detailing their marking location. All patients had BMC and only 11 had BMB. The CMO was a differential of this study and it allowed an expanded sample. In the TMA, 63.7% (58/91) of the samples were immunopositive for p53; and 35.2% (31/88) were immunopositive for p21. Nuclear staining, divergent from the literature, was observed in 17.3% (10/58) among those p53+ and in 38.7% (12/31) among those p21+. The pattern of immunostaining showed non-significant differences (P=0.474) regarding morphologic and clinical aspects. The positivity for both may indicate an effective balance between apoptosis and anti-apoptotic action. Excessive inhibition of apoptosis would contribute to high global cellularity, but without functional maturation effectiveness. In conclusion, there is p21 and/or p53 immunoexpression in most cases of this study and there is no clear association between immunoexpression pattern and patient outcome. Unlike the literature, we also found a percentage of nuclear immunostaining, but the finding was not statistically significant. Combination of p21 and p53 results created different possibilities of pathologic interpretation for MH, reinforcing the importance of studies similar to this one.

A Rat Model of Neurocysticercosis-Induced Hydrocephalus: Chronic Progressive Hydrocephalus with Mild Clinical Impairment.

BACKGROUND: Hydrocephalus is the most common complication of extraparenchymal neurocysticercosis, combining obstructive and inflammatory mechanisms that impair cerebrospinal fluid circulation. METHODS: We studied the long-term progression of neurocysticercosis-induced hydrocephalus in a rat model. We generated an experimental rat model of neurocysticercosis-induced hydrocephalus by cisternal inoculation of cysts or antigens of Taenia crassiceps and compared it with the classic model of kaolin-induced hydrocephalus. We used 52 animals divided into 4 groups: 1) control, 2) neurocysticercosis-induced hydrocephalus by cysts or 3) by antigens, and 4) kaolin-induced hydrocephalus. We studied behavioral, radiologic, and morphologic alterations at 1 and 6 months after inoculation by open field test, magnetic resonance imaging, and immunohistochemical localization of aquaporin-4 (AQP-4). RESULTS: Behavioral changes were observed later in neurocysticercosis-induced than in kaolin-induced hydrocephalic rats (P = 0.023). The ventricular volume of hydrocephalus induced by experimental neurocysticercosis progressively evolved, with the magnetic resonance imaging changes being similar to those observed in humans. Periventricular inflammatory and astrocytic reactions were also observed. AQP-4 expression was higher in the sixth than in the first month after inoculation (P = 0.016) and also occurred in animals that received antigen inoculation but did not develop hydrocephalus, suggesting that AQP-4 may constitute an alternative route of cerebrospinal fluid absorption under inflammatory conditions. CONCLUSIONS: Our neurocysticercosis-induced hydrocephalus model allows for the long-term maintenance of hydrocephalic animals, involving mild clinical performance impairments, including body weight and behavioral changes.

Bone Marrow Aspirate Clot: A Useful Technique in Diagnosis and Follow-Up of Hematological Disorders.

Bone marrow biopsy is a diagnostic tool largely used in the evaluation of a broad number of disorders that could affect the hematopoietic system. Differently, bone marrow aspirate clot technique is rarely performed even though it has been described in literature. Here, we highlight the utility of the bone marrow aspirate clot, exemplifying through the discussion of three clinical cases in which this technique was used for diagnosis and follow-up purposes: megaloblastic hemopathy, multiple myeloma, and chronic lymphocytic leukemia. Bone marrow clot analysis increases sensitivity to diagnose hemopathies and offers the possibility of morphological evaluation and anatomopathological study, with the advantage of not needing decalcification processes, hence improving antigenic expression in immunohistochemical and FISH techniques. It is an easy-to-perform technique, offering a quick, reliable, and more comfortable procedure for patients.

Case for diagnosis. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder.

Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a rare disease, with an indolent evolution and benign course. The classic presentation is a solitary nodule on the face or trunk. The disorder's rarity and clinical and histopathological characteristics, can make the diagnosis difficult. We present the case of a 36-year-old Caucasian woman with a purplish erythematous nodule, hardened, shiny, asymptomatic, on the left nasal ala, which had grown progressively for 45 days. Histopathological examination and immunohistochemistry panel demonstrated alterations consistent with primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. There was complete remission of the condition within 60 days of treatment with potent occlusive corticosteroids.

Case for diagnosis. Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder

Abstract: Primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder is a rare disease, with an indolent evolution and benign course. The classic presentation is a solitary nodule on the face or trunk. The disorder's rarity and clinical and histopathological characteristics, can make the diagnosis difficult. We present the case of a 36-year-old Caucasian woman with a purplish erythematous nodule, hardened, shiny, asymptomatic, on the left nasal ala, which had grown progressively for 45 days. Histopathological examination and immunohistochemistry panel demonstrated alterations consistent with primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder. There was complete remission of the condition within 60 days of treatment with potent occlusive corticosteroids.