Predicting Response to Neoadjuvant Chemotherapy Using 18F FDG PET-CT in Patients with Locally Advanced Breast Cancer.

OBJECTIVE: The study was aimed to find the utility of 18F FDG PET CT in assessing response to neoadjuvant chemotherapy (NACT) in female patients with locally advanced breast cancer (LABC). METHODS: All willing women with biopsy proven LABC, following clinical evaluation underwent baseline 18F FDG PET CT along with mammosonograpy and contrast enhanced computerized chest radiography (CECT). The response was assessed clinically before each cycle of chemotherapy using RECIST criteria. Those who were progressing clinically were offered alternate chemotherapy or radiation or surgery. Clinical responders were re-evaluated with 18F FDG PET CT, mammosonogram and CT chest before surgery. The pathological response as assed with residual cancer burden score was used as gold standard. RESULTS: Of the 30 women eligible, 26 women underwent repeat evaluation and surgery. The mean age was 49 years, 16 women were postmenopausal and 15 tumors were receptor positive. On final histopathology 15 % had completer response and 46 % were non responders. Using a cut off value of 50% of the baseline SUVmax, PET-CT had sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 64%, 75%, 75%, 65%, and 69%, respectively in differentiating pathological responders from non-responders. CONCLUSION: 18F FDG PET-CT predicted the response with greater accuracy than CT or clinical examination. Hence it can be used to identify non responders early in the course and alternate treatment can be offered to patients.

Whole-body 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) for staging locally advanced breast cancer: A prospective study from a tertiary cancer centre in south India.

Background & objectives: Locally advanced breast cancer (LABC) is associated with substantial risk of occult metastases. The patients with LABC have high rate of systemic relapse, suggesting inadequacy of the current conventional staging in detecting the occult metastatic spread. 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) is a new modality in the staging of breast cancer patients. Hence, this study was conducted to evaluate the role of 18F-FDG PET/CT in initial staging of LABC and to compare it with conventional methods. Methods: This prospective study included biopsy-confirmed female patients diagnosed with LABC meeting the selection criteria and attending surgical, medical and radiation oncology departments of a tertiary care centre in south India, from April 2013 to December 2014. Conventional workup included serum chemistry, mammogram, bone scan, contrast-enhanced CT (CECT) chest and upper abdomen and ultrasound abdomen and pelvis. All patients following conventional workup underwent 18F-FDG PET/CT. Results: In this study, 61 women with LABC underwent both conventional workup and 18F-FGD PET/CT. The 18F-FDG PET/CT, in comparison to conventional workup, revealed unsuspected N3 nodal disease in 11 more patients, revealed distant metastasis in seven more patients and also detected extra sites of metastasis in five patients. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of PET/CT to detect distant metastasis were 95, 98, 95, 98 and 97 per cent, respectively, whereas the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of conventional imaging to detect distant metastasis were 65, 93, 81, 84 and 84 per cent, respectively. Interpretation & conclusions: The 18F-FDG PET/CT was found to be more accurate than conventional imaging for staging and modified stage and treatment in 30 and 38 per cent of patients, respectively. It was particularly useful in detecting occult distant metastasis and N3 nodal disease with an added advantage of examining whole body in single session. However, CECT chest was superior over 18F-FDG PET/CT for detecting pulmonary metastasis.

A Prospective Study Comparing Functional Imaging (18F-FDG PET) Versus Anatomical Imaging (Contrast Enhanced CT) in Dosimetric Planning for Non-small Cell Lung Cancer.

OBJECTIVES: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET-CT) is a well-used and established technique for lung cancer staging. Radiation therapy requires accurate target volume delineation, which is difficult in most cases due to coexisting atelectasis. The present study was performed to compare the 18F-FDG PET-CT with contrast enhanced computed tomography (CECT) in target volume delineation and investigate their impacts on radiotherapy planning. METHODS: Eighteen patients were subjected to 18F- FDG PET-CT and CECT in the same position. Subsequently, the target volumes were separately delineated on both image sets. In addition, the normal organ doses were compared and evaluated. RESULTS: The comparison of the primary gross tumour volume (GTV) between the 18F-FDG PET-CT and CECT imaging revealed that 88.9% (16/18) of the patients had a quantitative change on the 18F-FDG PET-CT. Out of these patients, 77% (14/18) of the cases had a decrease in volume, while 11% (2/18) of them had an increase in volume on the 18F-FDG PET-CT. Additionally, 44.4% (8/18) of the patients showed a decrease by > 50 cm 3 on the 18F-FDG PET-CT. The comparison of the GTV lymph node between the 18F-FDG PET-CT and CECT revealed that the volume changed in 89% (16/18) of the patients: it decreased and increased in 50% (9/18) and 39% (7/18) on the 18F-FDG PET-CT. New nodes were identified in 27% (5/18) of the patients on the 18F-FDG PET-CT. The decrease in the GTV lymph node on the 18F-FDG PET-CT was statistically significant. The decreased target volumes made radiotherapy planning easier with improved sparing of normal tissues. CONCLUSION: GTV may either increase or decrease with the 18F-FDG PET-CT, compared to the CECT. However, the 18F-FDG PET-CT-based contouring facilitates the accurate delineation of tumour volumes, especially at margins, and detection of new lymph node volumes. The non-FDG avid nodes can be omitted to avoid elective nodal irradiation, which can spare the organs at risk and improve accurate staging and treatment.

Expression of p53 & epidermal growth factor receptor in glioblastoma.

BACKGROUND & OBJECTIVES: Glioblastoma (GB) is the most frequent brain tumour, manifesting at any age, with a peak incidence between 45 and 75 years. Primary and secondary GBs constitute relatively distinct disease entities in evolution, in expression profiles and in therapeutic response. Histopathologically, primary and secondary GBs are indistinguishable. The aim of this investigation was to study the immunohistochemical (IHC) expression of p53 and epidermal growth factor receptor (EGFR) in GB with the objective of categorizing the morphological variants of GB into primary and secondary based on the presence of low-grade areas and knowing the variable expression of p53 and EGFR in primary and secondary GB. METHODS: A total of 28 patients with GB were studied and categorized into primary and secondary based on the presence of low-grade areas, i.e. discernible astrocytic morphology, gemistocyte and oligodendroglia. Tumours with the presence of combination of the above features or any one of the above features were taken as secondary GB, whereas tumours with highly pleomorphic areas were considered as primary GB. IHC was done on the representative tissue blocks for p53 and EGFR. RESULTS: Majority of the patients were in the fifth and sixth decades of life with a mean age of 46.96±13 yr with male preponderance (male:female 2.5:1). Mean age of presentation was 48.93±12 yr in primary and 44.69±15 yr in secondary GB. All cases of GB were classified into primary (53.57%) and secondary (46.43%) based on morphology. EGFR was more frequently expressed than p53. Based on IHC, 50 per cent of cases were classified into primary, three per cent into secondary and 47 per cent as unclassified. INTERPRETATION & CONCLUSIONS: Histopathological features, i.e. presence of low-grade areas, may play a role in classifying GB into primary and secondary. EGFR has a pivotal role in gliomagenesis. Combination of p53 and EGFR alone may not be sufficient to clarify GB into primary and secondary.

A study of primary glomerular diseases in adults; clinical, histopathological and immunofluorescence correlations.

Introduction: The frequency of primary glomerular diseases is variable from one part of the world to the other. Data published from India has shown wide range of variation in the different regions of the country. Objectives: This study reports the frequency of primary glomerulonephritis (GN) in adults in the Rayalaseema region of south India. Materials and Methods: The study is based on prospective evaluation of renal biopsies done during 2 years 4 months period (May 2010-August 2012). A total of 137 cases of primary GN were studied by light microscopy and immunofluorescence (IF). The patients age range between 15-74 years. Results: Most frequent primary GN was membranous nephropathy (MN) constituting 35.8%, followed by minimal change disease (MCD) at 16.7%. Conclusion: This study demonstrates that MN is the most common primary GN encountered in the adults, the second more frequent is MCD. This result is in contrast to previous reports from India where IgA nephropathy (IgAN) and MCD were reported as the most common primary GN in whole population.

Utility of [18F] Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG PET/CT) in the Initial Staging and Response Assessment of Locally Advanced Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

In India up to 50 % of breast cancer patients still present as locally advanced breast cancer (LABC). The conventional methods of metastatic work up include physical examination, bone scan, chest & abdominal imaging, and biochemical tests. It is likely that the conventional staging underestimates the extent of initial spread and there is a need for more sophisticated staging procedure. The PET/CT can detect extra-axillary and occult distant metastases and also aid in predicting response to chemotherapy at an early point in time. To evaluate the utility of FDG PET/CT in initial staging and response assessment of patients with LABC receiving NACT. A prospective study of all biopsy confirmed female patients diagnosed with LABC receiving NACT from April 2013 to May 2014. The conventional work up included serum chemistry, CECT chest and abdomen and bone scan. A baseline whole body PET/CT was done in all patients. A repeat staging evaluation and a whole body PET/CT was done after 2/3rd cycle of NACT in non-responders and after 3/4 cycles in clinical responders. The histopathology report of the operative specimen was used to document the pathological response. The FDG PET/CT reported distant metastases in 11 of 38 patients, where as conventional imaging revealed metastases in only 6. Almost all the distant lesions detected by conventional imaging were detected with PET/CT, which showed additional sites of metastasis in 3 patients. In 2 patients, PET/CT detected osteolytic bone metastasis which were not detected by bone scan. In 5 patients PET CT detected N3 disease which were missed on conventional imaging. A total of 14 patients had second PET/CT done to assess the response to NACT and 11 patients underwent surgery. Two patients had complete pathological response. Of these 1 patient had complete metabolic and morphologic response and other had complete metabolic and partial morphologic response on second PET/CT scan. The 18 FDG PET/CT can detect more number of metastasis as well as additional sites of metastasis compared to conventional methods. The response assessment resulted in change of treatment regimen in 14 % of patients.

Acute renal failure in a patient with mantle cell lymphoma.

Mantle cell lymphoma is a rare form of B-cell lymphoma. We present a 54-year-old gentleman with mantle cell lymphoma. It was diagnosed based on the demonstration of B-cell antigens CD20 and CD5. It was further confirmed by demonstration of overexpression of cyclin D1 on these atypical lymphocytes in the immunohistochemical staining. He also had acute renal failure and proteinuria. Renal biopsy revealed crescents and lymphomatous infiltration of tubulointerstitium. The presence of infiltrating cells with similar markers in both the lymph node and the kidney confirmed the infiltration of kidney with lymphomatous cells. Our present patient, after a thorough literature search, is found to be the second one with a glomerular lesion and tubulointerstitial infiltration by malignant lymphoma cells.

Cutaneous metastasis of transitional cell carcinoma of the urinary bladder: Cytological aspect.

Cutaneous metastasis from transitional cell carcinoma urinary bladder is a rare clinical entity associated with poor prognosis. This case report describes a 51-year-old male who presented with multiple cutaneous metastases arising from high grade transitional cell carcinoma bladder with lamina propria invasion. The prominent cytological features include medium sized to large pleomorphic cells with irregular nuclear outlines, coarse chromatin pattern, and tumor giant cells. An awareness of this rare clinical entity and high index of suspicion is needed for diagnosis.

Novel frame shift mutations ('A' deletion) observed in exon 9 of Wilms' tumor (WT1) gene in a patient reported with glomerulosclerosis.

Wilms' tumor-suppressor gene-1 (WT1) is a transcription factor that contains four zinc-finger motifs at the C-terminus and plays a crucial role in kidney and gonad development. We have identified primitive glomeruloid formation using immunohistochemistry in a patient who was clinically diagnosed with a Wilms' tumor. In order to understand the involvement of mutations in the WT1 gene, the genomic DNA was isolated from peripheral blood of the patient (18/F). Exon 9 of the WT1 gene was amplified and sequenced. The obtained sequence was BLAST searched against the transcript variants (TV) of the WT1 gene. An amplified exon 9 sequence of the WT1 gene showing similarity with exon 9 of TV-A, F and exon 10 of TV-B, D and E with a deletion of single nucleotide 'A' causing frame shift in the 4th zinc finger domain of the WT1 protein resulted in Wilms' tumor condition. The deletion position is variable with different transcript variants and they are present at: for TV-A c.1592delA, p.468, for TV-F c.1053delA, p.259, for TV-B c.1643delA, p.485, for TV-D c.1652 delA, p.488, and for TV-E c.1095delA, p.273; all these variations resulted in frame shift mutation. In order to substantiate these results in silico analysis was carried out; the structural superimposition of wild type and mutant WT1 structures showed that the mutated region exhibited a different confirmation with RMSD of 1.759Å. Therefore, these results conclusively explain the mutation in the WT1 gene that leads to structural changes contributing to glomerulosclerosis.

Synovial sarcoma with relevant immunocytochemistry and special emphasis on the monophasic fibrous variant.

BACKGROUND: Monophasic fibrous synovial sarcoma (SS) is the most common variant of SS. Only a few cytological studies are available on this entity. Bcl-2 protein expression has been described as a characteristic marker of SS and is useful for its differentiation from other sarcomas. Cytokeratin and CD99 are also used in detecting SS. AIMS: To evaluate synovial sarcoma and its variants cytomorphologically. MATERIALS AND METHODS: During a period of 10 years 7 months, i.e. from January 1998 to July 2008, 12 cytologic specimens diagnosed as synovial sarcoma were reviewed. Ten cases were diagnosed as SS on aspiration alone but two cases required ancillary technique i.e., immunocytochemistry staining with bcl-2 and cytokeratin. The smears were stained with Papanicolaou and May-Grünwald-Giemsa stains. RESULTS: All cytologic specimens in our study had similar appearance. Most smears were highly cellular and were made up of densely packed tri-dimensional groups and singly scattered round to oval cells. Cellular monomorphism and vascular channels within the cell groups were the remarkable findings. Only one case showed cytologic evidence of epithelial differentiation. Bcl-2, cytokeratin, CD99 positivity was seen on immunohistochemistry staining. Results were categorized according to age, sex and morphologic variants. CONCLUSIONS: Although cytomorphologic features of synovial sarcomas are characteristic enough to permit its recognition, clinical correlation is necessary for accurate diagnosis. Monophasic variant is the most common entity observed in the present study.