Role of S100 A7 as a diagnostic biomarker in oral potentially malignant disorders and oral cancer.

Background: S100 proteins have been implicated in the tumorigenesis of different human cancers and in oral dysplasia, as they are keratinocytes. Materials and Methods: In the present study, we have attempted to compare the expression of S100-A7 within young-onset (age ≤45 years, Group 1) oral squamous cell carcinoma (OSCC), OSCC in older age groups (age >45 years Group 2), oral potentially malignant disorders (OPMDs, Group 3) and inflammatory lesions (Group 4). The tissue sections were scored based on the percentage of immunostained cells and staining intensity. Nuclear, cytoplasmic and membrane immunoreactivity were also scored. Results: The present study comprised 153 histopathologically diagnosed case subjects of OSCC >45 years (n = 41), OSCC <45 years (n = 36), OPMD (n = 40) and inflammatory lesions (n = 36). The present study revealed a statistically significant difference of distribution with regard to S100A7 staining (cytoplasmic and nuclear) between OPMDs and OSCC (P < 0.05). The nuclear, cytoplasmic and membrane staining as well as the staining intensity had significantly different scoring patterns among the OSCC group, OPMD group and the inflammatory lesions with the OSCC group having the highest scoring of the S100A7 staining (irrespective of the age). Conclusions: The present study concludes that S100A7 can be used as a diagnostic biomarker to differentiate between OPMDs and OSCC lesions. However, the marker is unable to distinguish between OSCCs in younger and older patients as the molecular pathogenesis of tumors in either of these age groups is probably similar.

Ultrasound liver elastography for the detection of liver fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy: A cross-sectional study.

BACKGROUND: Long-term low-dose methotrexate therapy is associated with liver fibrosis. Although liver biopsy is the gold standard for detecting fibrosis, it is an invasive procedure associated with morbidity and mortality risks. Hence noninvasive imaging techniques such as transient elastography (TE) and shear wave elastography (SWE) have been studied to measure liver stiffness. AIMS: To assess the utility of TE and SWE in detecting fibrosis in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. METHODS: A cross-sectional prospective study was undertaken on 54 patients with psoriasis and reactive arthritis who had received ≥1.5 g of methotrexate. Various clinical and biochemical [fibrosis 4 index (FIB4), aspartate-transaminase-to-platelet ratio index (APRI)] parameters were calculated and liver stiffness measurement (LSM) was done with TE and SWE. The degree of steatosis was measured using controlled attenuation parameter (CAP). Liver biopsy was done when indicated and was interpreted by a pathologist blinded to clinical and imaging results. RESULTS: Fifty four patients with a mean age of 40.3 years and a male-to-female ratio of 5:1 were included. The mean cumulative methotrexate dose was 3.04 g. The median FIB4, APRI, and gamma-glutamyl transpeptidase-to-platelet ratio values were 0.75, 0.23, and 0.15, respectively. The median LSM for TE and SWE was 5.3 and 7.32 kPa, respectively. SWE and TE showed a weak positive correlation (r = 0.26, P = 0.053). The mean CAP was 217 dB/m (area under the receiver operating characteristic = 0.70). In the 19 of 26 cases whose liver biopsies could be assessed, only 4 (21%) showed F1 fibrosis (Ishak staging). The median LSM on SWE was significantly higher in patients with a cumulative methotrexate dose ≥ 4 g when compared with those with a dose <4 g (9.85 vs 7.1, P = 0.02). Other parameters did not correlate with TE and SWE. LIMITATIONS: The small sample size and the low number of cases with significant fibrosis on histopathology were the major limitations of this study. CONCLUSION: Histologically detectable LF is uncommon in patients with psoriasis and reactive arthritis on long-term methotrexate therapy. Both TE and SWE are good at detecting the absence of fibrosis in these patients. In our study, SWE and TE values did not correlate with clinical, biochemical, or histopathological parameters.

Antitubercular Therapy Given to Differentiate Crohn's Disease From Intestinal Tuberculosis Predisposes to Stricture Formation.

BACKGROUND AND AIM: Treatment trial with antitubercular therapy [ATT] is a common strategy in tuberculosis-endemic countries in case of a diagnostic dilemma between intestinal tuberculosis and Crohn's disease [CD]. Our aim was to determine the long-term clinical course of patients who received ATT before an eventual diagnosis of CD was made. METHODS: We performed retrospective comparison between CD patients who received ≥6 months of ATT vs those who did not receive ATT. Outcomes assessed were change in disease behaviour during follow-up, requirement of surgery and medication use. RESULTS: In all, 760 patients with CD were screened for the study and, after propensity matching for location and behaviour of disease, 79 patients in each group were compared. Progression from inflammatory [B1] to stricturing/fistulising [B2/B3] phenotype was increased among CD patients who received ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 41.8%, 51.9%, 6.3% at follow-up, respectively] as compared with those who did not receive ATT [B1, B2, B3: 73.4%, 26.6%, 0% at baseline vs: 72.2%, 27.8%, 0% at follow-up, respectively] with an odds ratio of 11.05[3.17-38.56]. The usage of 5-aminosalocylates, steroids, immunosuppressants and anti-tumour necrosis factor was similar between both the groups. On survival analysis, CD patients who received ATT had a lower probability of remaining free of surgery [45%] than those who did not [76%] at 14 years of follow-up (hazard ratio [HR] = 3.22, 95% confidence interval [CI], 1.46-7.12, p = 0.004]. CONCLUSIONS: Crohn's disease patients diagnosed after a trial with antitubercular therapy had an unfavourable long-term disease course with higher rate of stricture formation and less chance of remaining free of surgery.

Cytocentrifuged biopsy fixative preparation: A simple cost-effective technique facilitating microscopic diagnosis of lumen-dwelling intestinal parasites.

OBJECTIVE: Direct microscopic visualization is the most specific method for detecting intestinal parasites and is commonly achieved by stool examination or mucosal biopsy. However, postfixation, the intestinal biopsy fragment is often curled, and the entire surface of the biopsied mucosa is seldom viewed microscopically. Tissue processing further distorts morphology of the organisms and causes diagnostic difficulties. Examining multiple sections for parasite detection is time-consuming and often requires aid of special stains and/or immunohistochemistry. To overcome these disadvantages, we hypothesized that the fixative in which biopsies are transferred may provide a valid representation of the biopsied mucosal surface and therefore aid in the identification of mucosal surface parasites. MATERIALS AND METHODS: Formalin in which biopsies were transferred was retained, stored at 4°C and processed with a cytocentrifuge. Totally, 120 consequent duodenal biopsy fixatives were processed in this way and the cytocentrifuged smears visualized after May-Grunwald-Giemsa staining. Findings of these smears were correlated with their corresponding formalin fixed paraffin embedded tissue sections. RESULTS: Cytocentrifuged formalin preparations were found to be representative of the mucosal surface contents. Giardia trophozoites were visualized in 10/120 preparations with distinct morphological characteristics which were seldom appreciable in tissue sections, eliminating the need for special stains. Furthermore, two of the corresponding histology sections did not demonstrate the parasites despite step sections, while in one case few parasites could be identified in the step sections. CONCLUSIONS: Cytocentrifuged fixative preparation is a simple and cost-effective technique which can be routinely employed for intestinal parasite characterization.

Overt and occult vidian canal involvement in juvenile angiofibroma and its possible impact on recurrence.

BACKGROUND: Postexcision residual disease in the vidian canal is speculated to contribute to recurrence in juvenile angiofibroma. METHODS: We composed a prospective cohort of 16 consecutive patients with juvenile angiofibroma (stages IIA-IIIB). The presurgical vidian canal assessment was done by contrast-enhanced CT (1.2 mm collimation). At surgery after complete tumor excision, the vidian canal tissue was sampled for histology. Postexcision drilling of the vidian canal was done in 8 of 15 patients to remove microscopic residual disease, with a 24 to 48 month follow-up period. RESULTS: Presurgical radiology indicated ipsilateral vidian canal enlargement (≥3 mm)/destruction in 13 of 16 patients. Radiologically occult involvement was documented only by histology in another 1 of 16 patients. Postexcision sampling of the vidian canal noted microscopic residual tumor in 3 of 15 patients. No recurrences were noted in 8 cases (0 of 8) with postexcision drilling of the vidian canal and 2 recurrences in 7 cases (2 of 7) with no drilling (p = .20). CONCLUSION: Vidian canal involvement in juvenile angiofibroma is almost universal (14 of 16) and may be occult to CT evaluation. The site may harbor microscopic residual tumor after seemingly complete excision. Surgical attention toward it may reduce recurrences. © 2015 Wiley Periodicals, Inc. Head Neck 38: E421-425, 2016.

Tumour morphology after neoadjuvant chemotherapy as a predictor of survival in serous ovarian cancer: an experience from a tertiary care centre in India.

Serous ovarian cancer is the most common malignant ovarian tumour. Traditional management consists of surgical resection with postoperative chemotherapy. Currently neoadjuvant chemotherapy is offered to patients with advanced stage disease. The present study aims to analyse the histomorphological alterations in serous ovarian cancer following neoadjuvant chemotherapy. Correlation of these morphological alterations with survival is also presented here. Serous ovarian cancers from 100 advanced stage cases were included; 50 were treated with pre-surgery chemotherapy. Semi-quantitative scoring was used to grade the alterations in tumour morphology. Survival data was correlated with the final morphological score. Tumour morphology was significantly different in cases treated with neoadjuvant chemotherapy (CT group) as compared to cases with upfront surgery. The CT group cases showed more fibrosis, calcification, and infiltration by lymphocytes, plasma cells, foamy and hemosiderin-laden macrophages. The residual tumour cells had degenerative cytoplasmic changes with nuclear atypia. Patients with significant morphological response had a longer median survival, although it did not attain statistical significance in the current study. With the increasing use of neoadjuvant chemotherapy in management, the pathologist needs to be aware of the altered morphological appearance of tumour. Further studies are required to establish a grading system to assess the tissue response which can be helpful in predicting the overall therapeutic outcome and the prognosis of patients.

Apoptotic protein expression, glycogen content, DNA ploidy and cell proliferation in hepatoblastoma subtyping and their role in prognostication.

PURPOSE: To evaluate Bcl-xL, Bax, PCNA, cytokeratin 19 (CK-19), glycogen content and DNA ploidy expression in hepatoblastoma (HB) and their prognostic value. METHODS: This retrospective study on 26 cases of HB involved DNA ploidy estimations separately for various subtypes on histological sections using image cytometry of Feulgen-stained smears. Glycogen content, PCNA, CK-19, Bax and Bcl-xL expression on tissue sections were evaluated. THE outcome on follow-up (mean 86 months) and Kaplan-Meier survival analysis were performed. RESULTS: Fetal areas were diploid (84%); embryonal areas were aneuploid (89.47%) (p < 0.001). PCNA labeling index was low in fetal (10.82%) and high in embryonal areas (59.85%) (p = 0.03). CK-19 was negative in fetal, but focally positive in embryonal areas. Bax was negative in fetal (80%) and positive in embryonal areas (88.23%) (p < 0.001); Bcl-xL was more frequently positive in fetal (90%) than embryonal areas (52.94%) (p = 0.02). Fetal cells were rich in glycogen. Kaplan-Meier survival analysis showed good initial radiological response to chemotherapy (p = 0.009), glycogen content (p = 0.0137) and DNA diploid cases (p = 0.0429) were associated with good outcome on univariate analysis. Histology typing (p = 0.085), Bcl-xL (p = 0.689), Bax (p = 0.27), CK-19 (p = 0.281), PCNA (p = 0.689), age (p = 0.24), sex (p = 0.5661), stage (p = 0.24) and α-fetoprotein levels (p = 0.49) were unrelated to outcome. Multivariate analysis showed glycogen content to be the most statistically significant variable (0.024). CONCLUSION: Fetal and embryonal areas show different staining patterns for PCNA, Bax and Bcl-xL. DNA ploidy and glycogen content are significant prognostic variables.

Bilateral primary renal lymphoma with orbital metastasis in a child.

Primary renal lymphoma (PRL) is a rare condition and bilateral PRL even rarer. Most of these bilateral PRL have been reported in adults. We describe a 3-year-old male with bilateral primary renal B cell lymphoma with orbital metastases. We discuss the difficulties in diagnosis and management of this rare presentation of lymphoma.

Sarcoidosis manifesting as massive splenomegaly: a rare occurrence.

Sarcoidosis is a multisystemic granulomatous disease of unknown origin occurring worldwide and affecting people of all races and ages. This disease manifests most frequently with bilateral hilar lymphadenopathy, pulmonary infiltrates, and skin and ocular lesions. Granulomatous inflammation of the spleen is common in patients with sarcoidosis, but splenic enlargement is unusual and massive splenomegaly quite rare. Splenomegaly is usually homogeneous, but multiple low-attenuating nodular lesions are occasionally seen and easily mistaken for lymphoma, metastases, or infections such as tuberculosis. We describe an unusual case of sarcoidosis in a woman who presented with massive splenomegaly with extensive nodularity that cleared completely with corticosteroid therapy.