Neoadjuvant denosumab: its role and results in operable cases of giant cell tumour of bone.

AIMS: The aims of this study were to evaluate the efficacy of preoperative denosumab in achieving prospectively decided intention of therapy in operable giant cell tumour of bone (GCTB) patients, and to document local recurrence-free survival (LRFS). PATIENTS AND METHODS: A total of 44 patients received preoperative denosumab: 22 to facilitate curettage, 16 to facilitate resection, and six with intent of converting resection to curettage. There were 26 male and 18 female patients. The mean age was 27 years (13 to 47). RESULTS: The mean number of denosumab treatments was five (2 to 7) per patient. In 42 of 44 patients (95%), denosumab helped to achieve prospectively decided intention. A total of 41 patients were available for follow-up at a mean follow-up of 34 months (24 to 48). There were 12 local recurrences (29%), in 11 patients (11/25, 44%) who had curettage and in one patient (1/16, 6%) who had resection. The mean time to local recurrence was 16 months (8 to 25). The LRFS was 76% at two years: 94% for cases with resection and 64% for cases with curettage (p = 0.013). CONCLUSION: Although local control rates are unlikely to improve with use of preoperative denosumab, a short preoperative course of denosumab can facilitate surgery in certain cases of operable GCTB, with a high risk of local recurrence making curettage or resection technically easier. It may also help in converting a lesion requiring resection to a lesion that could possibly be treated with curettage.

Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors.

AIMS: To review various pathologic parameters in diagnosed cases of trunk and extremity-based soft tissue tumors (STTs), in order to identify concordance rate between initial biopsy and resection specimen and discrepancies between initial and review diagnosis, by a specialist pathologist. MATERIALS AND METHODS: Over a 2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including referral and "in-house" cases were studied. The reviewing specialist pathologist was blinded to the initial diagnoses. Discordances including discrepancies and deficiencies were defined as major and minor. Major discrepancies included those that could lead to significant treatment changes. True discrepancies were those related to sampling issues between the biopsies and resection specimens. Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor size, and marginal status (in resections) were subdivided as major and minor. RESULTS: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma) and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs, liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were relatively more frequently associated with discrepancies. Percentage of cases with major discordances between the referral reports (100 cases) and review diagnosis was 60%. Percentage of cases with major discordances between the specialist and other oncopathologists was 11%. True discrepancies were observed in 20 (5%) cases. The association of type of specimen with the rate of discordance was not significant (P = 0.114). CONCLUSIONS: Diagnoses of STTs are fraught with errors mostly from general pathologists, followed by nonspecialist oncopathologists. These findings reinforce the need for reporting of STTs, especially sarcomas, by specialist pathologists.

Does magnetic resonance imaging accurately predict residual disease after unplanned excision of soft-tissue sarcomas?

BACKGROUND: Often, it is difficult to assess the presence of residual disease after an unplanned excision in soft-tissue sarcomas. Inadequate excision leads to disease recurrence and inferior oncological outcomes while unnecessary excision may lead to additional surgical procedures with inherent morbidity and increased cost of treatment. There is a paucity of literature comparing the preoperative imaging findings with the final histopathology report to accurately assess the presence of residual disease. MATERIALS AND METHODS: The clinical details of 55 patients who had oncological scar excision after unplanned prior excision were retrieved. Histopathological evaluation of scar was compared with presurgery magnetic resonance imaging (MRI) for the presence of residual disease. Sensitivity, specificity, and positive and negative predictive value (NPV) of MRI for detection of residual disease were calculated. RESULTS: On MRI, residual disease was seen in 28 cases, no disease in 24 cases whereas findings of three patients were indeterminate. On final histopathology, residual disease was present in 30 (55%) patients whereas no residual tumor was seen in 25 (45%) patients. Two patients in whom MRI suggested the presence of residual disease had no tumor on final histopathology. No evidence of residual disease was reported in MRI of 24 patients. Of these, twenty patients were confirmed to have no tumor on final histopathology, whereas four patients had a residual tumor. Sensitivity: 86.66%, specificity: 90.90%, positive predictive value (PPV): 92.85%, NPV: 83.33%. CONCLUSION: MRI can aid in preoperative planning by identifying the site and extent of the previous surgery. It has a high PPV (92%) for detection of residual disease. However, a negative scan (NPV 83%) does not reliably exclude the presence of residual disease.

An audit of histopathology reports of carcinoma endometrium: experience from a tertiary referral center.

BACKGROUND: The aim was to assess compliance to reporting minimum data sets in carcinoma endometrium reports, in a team of 13 pathologists, and also to analyze parameters such as. tumor size, type, grade, depth of myometrial invasion, lymph node yield, pTNM stage etc. MATERIALS AND METHODS: Reports of 114 cases of carcinoma endometrium, that were operated in-house during the years 2008 to 2010 were analyzed from the files of the Pathology department of our hospital. RESULTS: The median age was 58.04 years and median tumor size was 4 cm. Endometrioid adenocarcinoma was the most common type (82.5%), followed by malignant mixed Mullerian tumor (MMMT) (6.1%) and Serous carcinoma (3.5%). Grade 2 was the commonest tumor grade (42.1%). Less than half of myometrial invasion was seen in 50% of the cases and more than half of the myometrial invasion was seen in 46.5% of cases. (Information was not available in four cases). Parametrial involvement was seen in 5.3% cases. The pTNM stage was not mentioned in 71.9% reports. The median lymph node yield was 15. CONCLUSION: The compliance to adhere to and to provide minimum data information in carcinoma endometrium reports is generally good. Lymph node yield is reasonable. Mentioning of pTNM staging is to be done more meticulously. Use of proformas/checklists is recommended.

Outcome of gestational trophoblastic neoplasia: experience from a tertiary cancer centre in India.

AIMS: Gestational trophoblastic neoplasms (GTN) comprise a spectrum of interrelated conditions originating from the placenta. With sensitive assays for human chorionic gonadotropin (ß-hCG) and current approaches to chemotherapy, most women with GTN can be cured with preservation of reproductive potential. The purpose of this analysis was to address the outcome of GTN from a developing country, as data are largely sparse from this region. MATERIALS AND METHODS: We undertook a retrospective review of GTN cases treated at our centre from 2001 to 2008. Patients of GTN were assigned to low-risk (score ≤ 6) or high-risk (score ≥ 7) categories as per the modified World Health Organization scoring system. The low-risk group was treated with single-agent methotrexate (MTX) and the high-risk group received the EMA/CO regimen. Salvage therapies were EMA/EP or BEP. Treatment was continued until serum ß-hCG values were normal for three consecutive chemotherapy cycles, after which the patients were kept on follow-up. RESULTS: In total, 70 GTN patients were treated at our institution during this period; 48 (68%) were low-risk and 22 (32%) were in the high-risk category. The median ß-hCG level was 50 000 IU/l. The lung was the most common site of metastasis, seen in 15 (21%) patients. Among 48 low-risk patients, 37 (77%) received chemotherapy, of whom 25 (68%) were treated with MTX and 24 (96%) achieved a complete response. Twelve low-risk patients (32%) received EMA/CO therapy; 10 (83%) achieved a complete response. The 22 high-risk patients received EMA/CO and of these 16 (73%) achieved a complete response, two (9%) progressed, two (9%) died of progressive disease and two (9%) were lost to follow-up. Grade 3/4 toxicities with MTX included mucositis in two (8%) and neutropenia in five (21%) patients. At a median follow-up of 16.6 months, overall survival in the low- and high-risk groups was 100 and 88.8%, respectively. CONCLUSION: Risk-stratified treatment of GTN was associated with acceptable toxicity and resulted in outcome that was comparable with international standards.

Identification of atypical glandular cells in pap smears: is it a hit and miss scenario?.

OBJECTIVE: Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign. STUDY DESIGN: A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background. RESULTS: This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%. CONCLUSIONS: A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.

A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs.

BACKGROUND: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. AIMS AND OBJECTIVES: To review histologically all metastatic sarcomas to lung and compare with the primary where available. MATERIALS AND METHODS: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. RESULTS: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. CONCLUSIONS: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.

A t (11; 22) (p13; q12) EWS-WT 1 positive desmoplastic small round cell tumor of the maxilla: an unusual case indicating the role of molecular diagnosis in round cell sarcomas.

A desmoplastic small round cell tumor (DSRCT) is an uncommon tumor characterized by polyphenotypic expression and a specific reciprocal translocation t (11; 22) (p13; q12). It has been rarely identified in the head and neck region. Herein, we describe a DSRCT in the maxilla of a young man, who was initially diagnosed with a primitive neuroectodermal tumor (PNET), based on histopathological appearance of a round cell tumor, with MIC2 and -FLI-1 positivity, on immunohistochemistry (IHC). Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT-PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1. The case is presented to highlight the value of molecular diagnosis in round cell sarcomas at uncommon sites, especially when similar IHC markers can be expressed in a PNET and a DSRCT. An exact diagnosis of a round cell sarcoma has a therapeutic relevance.

Expression of E-Cadherin in breast carcinomas and its association with other biological markers - a prospective study.

CONTEXT: E-cadherin (E-CD) is an important cell adhesion molecule in normal epithelial cells and has been shown to be an invasion tumor suppressor gene. MATERIALS AND METHODS: Various clinicopathological parameters like age, family history, tumor stage, histological grade, lymph node status and other biological markers were also analyzed. Present study reveals E-CD expression in 65 cases of breast cancer including 41 (63%) cases of pure infiltrating ductal carcinoma (IDC), 11 (16.9%) of pure infiltrating lobular carcinoma (ILC); another 10 (15.3%) of mixed ductal/lobular type, and remaining 3 (4.6%) miscellaneous types. RESULTS: Negative E-CD expression was noticed more in advancing age groups (P = 0.01). About 59.2% cases showing negative E-CD expression had family history of breast and/or other cancers. E-CD expression was found significantly higher in cases of pure IDC (55.5%) than in pure ILC cases (18.1%) (P = 0.04). Eleven (68.7%) of the total 16 high-grade IDC cases, revealed negative expression. Both cases of comedo carcinoma revealed negative expression. Three (30%) out of 10 mixed cases revealed negative expression in both ductal and lobular areas, while in remaining 7 cases, positvity was seen in ductal areas only. Invasive cribriform and medullary carcinoma revealed a stronger expression, while negative staining was observed in sweat gland carcinoma. E-CD re-expression was noticed in lymph node tumor deposits. A direct association of E-CD expression with ER expression and an inverse association with that of p53 were also observed (P = 0.001), (P = 0.04). CONCLUSIONS: E-CD expression is useful, but limited, in differentiating IDCs from ILCS. Its negative expression correlates with certain poor prognostic parameters reflecting its use as a marker for invasive cancers. It re-expresses at metastatic sites.

The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears.

OBJECTIVES: A diagnosis in pulmonary onco-cytopathology primarily necessitates distinguishing small cell carcinoma (SCLC) from non-small cell carcinoma (NSCLC), which includes squamous cell carcinoma and adenocarcinoma. Lately, p63 antibody has been used for distinguishing squamous cell carcinoma from SCLC and adenocarcinoma. We present an analysis of p63 expression in cytological smears from 100 bronchial lavage specimens comprising 51 cases of SCLC and 49 cases of NSCLC. METHODS: A single Papanicolaou-stained conventional smear was de-stained and re-fixed with cold acetone and methanol for immunocytochemical staining with p63 antibody. Staining results were graded as 0 (nil), 1+ (focal), 2+ (moderate, diffuse) and 3+ (strong, diffuse). RESULTS: Out of 100 cases, 21 were cytologically diagnosed as squamous cell carcinoma. Twenty of these showed 2+ or 3+ p63 positivity, whereas one, which was adenocarcinoma on histology, showed 1+ staining. Of seven cases cytologically diagnosed as adenocarcinoma, six showed no p63 staining, whereas one, which was squamous cell carcinoma on histology, showed 1+ staining. All 48 cases cytologically diagnosed as SCLC were confirmed as such on histology and showed no p63 staining. Four cases were cytologically designated as poorly differentiated carcinomas, of which three showed no p63 staining and one showed 3+ staining. The former three were found to be SCLC on histology while the latter was squamous cell carcinoma. The remaining 20 cases were cytologically designated as NSCLC. Of these, eight showed no p63 staining, whereas 10 showed 1+ and two showed 2+ staining. The former eight were adenocarcinoma on histology and the latter two were squamous cell carcinoma. The 10 cases that showed 1+ p63 staining were adenocarcinomas (n = 5), squamous cell carcinoma (n = 4) and NSCLC, not otherwise specified (n = 1). Positive staining was seen in normal basal cells, which acted as an internal control. Overall sensitivity of p63 for squamous cell carcinoma was 100% and specificity was 90.4%. CONCLUSIONS: p63 immunostaining on processed cytology smears can be used to help identify squamous cell carcinoma. Its diffuse expression was specific for squamous cell carcinoma while focal staining was also seen in adenocarcinoma.

A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: a rare case report with review of literature.

Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have dealt with molecular analysis. A 19-year-old boy presented with pain and swelling in his left lower limb of two months duration. He developed acute urinary retention four days prior to his hospital admission, wherein radiological examination unraveled a large soft tissue mass, displacing his pelvic muscles, along with a lytic lesion involving his right pubic bone. Biopsy showed a cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive. Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value of molecular analysis in diagnosis of a synovial sarcoma at rare sites, especially when IHC results are equivocal and the biopsy material is limited.

Cytomorphological study of soft tissue neoplasms: role of fluorescent immunocytochemistry in diagnosis.

OBJECTIVES: Exact categorization of soft tissue tumours (STTs) on smears requires application of various ancillary techniques. This study was aimed at evaluating the role of fluorescent immunocytochemistry (FICC) in cyto-diagnosis of 30 STT cases. METHODS: Thirty cases of soft tissue tumours were included in the present study. All cases were subjected to routine Giemsa and Papanicolaou stain. Extra smears were made and kept for fluorescent immunostaining. A panel of cytoskeletal antibodies, tagged with FITC (Fluorescein isothyocynate), was employed in all these cases. Fluorescent immunostained smears were examined under Zeiss Confocal Laser scanning microscope, using double immunofluorescence (red-green). Finally, all cases were subjected to biopsy and again immunoperoxidase staining. RESULTS: Among the 30 cases in the present study, unaided cytological diagnoses ranged from 'spindle cell' tumour in four (13.3%) cases, benign and malignant spindle cell tumour in 17 (56.6%) cases, to malignant mesenchymal tumour in nine (30%) cases. FICC helped in further correct categorization of 25/30 (83.3%) cases viz. leiomyoma (three), benign neurogenic tumour (six), schwannoma (one), dermatofibrosarcoma protuberans (three), synovial sarcoma (two), rhabdomyosarcoma (two), malignant fibrous histiocytoma (five) and malignant peripheral nerve sheath tumour (three). Aggressive fibromatosis was found to be a missed diagnosis in two cases. Overall concordance between cyto-diagnosis with FICC, and histopathology results was 83.3% (P < 0.05). CONCLUSION: Fluorescent immunocytochemistry is a significant ancillary technique for making a rapid and specific diagnosis of STT, as required for their timely management. Incorporation of a wide panel of antibody markers with clinico-cytological correlation is recommended in forming an exact diagnosis in these cases.

Premalignant lesions of prostate and their association with nodular hyperplasia and carcinoma prostate.

BACKGROUND: A relatively new development in the arena of prostatic histopathological study is the premalignant proliferative changes in the glandular epithelium, possibly relating to carcinoma. Two major categories have come up, namely prostatic intraepithelial neoplasia (PIN) and atypical adenomatous hyperplasia (AAH). AIMS: The aims of present study were to identify foci of the two putative premalignant conditions viz. PIN and AAH in ducto-acinar lining epithelia of 200 prostatectomy specimens and their association with nodular hyperplasia and adenocarcinoma prostate. MATERIAL AND METHODS: Micro sections from 200 prostatectomy specimens, received in the Department of Pathology, PGIMS, Rohtak, were extensively studied for the presence and association of premalignant conditions. Significant values were obtained by employing Chi-square (chi2) test, with P value < 0.05 as significant. RESULTS: Out of 177 cases of nodular hyperplasia, 53 (29.9%) showed PIN and 38 (20.3%) showed presence of AAH. All 6 cases (100%) of pure carcinoma revealed foci of PIN. Out of the remaining 23 cases of carcinoma with nodular hyperplasia, foci of PIN were observed in 16 cases (94.1%) and AAH in 2 cases (11.7%). High-grade PIN was observed in 20 cases (86.9%) of the total 23 cases of carcinoma, with/without nodular hyperplasia and 20 cases (11.2%) of nodular hyperplasia. Low-grade PIN was observed in 33 cases (18.6%) of nodular hyperplasia and in only 1 case (5.8%) of carcinoma prostate with nodular hyperplasia. CONCLUSION: PIN, especially high-grade type was the most commonly observed premalignant lesion, in cases of adenocarcinoma, thereby suggesting it to be the likely precursor of carcinoma prostate. AAH showed a weaker association with carcinoma.