Well-differentiated liposarcoma of tongue: A case report.

Key Clinical Message: It is important to consider WDLS as a potential cause of tongue lesions and include it in the list of differential diagnoses. When performing surgical intervention, it is crucial to remove enough tissue around the lesion, and regular follow-up is necessary due to the high risk of recurrence, despite its rarity, when margins are positive. Abstract: Liposarcoma (LS) is the most common soft tissue sarcomas (STSs) that arise from embryonic mesenchymal tissue. Though these sarcomas commonly arise at retroperitoneal locations and extremities, the appearance of these tumors in the head and neck region is rare, with the tongue as a preferred site. As per WHO 2020, LS is classified into four subtypes based on morphology, namely, Well-differentiated liposarcoma (WDLS), Dedifferentiated liposarcoma (DDLS), Myxoid liposarcoma (MLS), and Pleomorphic liposarcoma (PLS). WLS is the most common variant among all. Here, we had a case of 55 years old male with the complaint of swelling in the left lateral border of the tongue with the preliminary diagnosis of pleomorphic adenoma. The patient underwent a left partial glossectomy with adequate margins. Further evaluation of the lesion revealed a clear cell tumor that was ultimately confirmed as liposarcoma on immunohistochemistry that showed tumor cells positive for S100, CDK4, and MDM2 with 2% Ki-67. Postsurgical status of the patient was evaluated by F18 FDG PET CTscan, which was normal. Currently, the patient is under regular follow-up.

Association of pro-inflammatory cytokines with trauma and post-traumatic stress disorder visiting a tertiary care hospital in Kathmandu.

Post-traumatic stress disorder (PTSD) is a mental disorder that can occur after trauma. Although inflammatory markers such as cytokines are found altered in trauma and PTSD, there is no consensus regarding which can be considered as biomarkers. Studies from South Asia region is also rare. We studied cytokines among trauma affected patients and matched healthy controls. Fifty patients (cases) with trauma, visiting the University hospital in Kathmandu and thirty-nine healthy controls were selected, and the levels of cytokines were determined using a Luminex IS 200. We compared the levels of the cytokines in thirty-four age and gender matched pairs of case and control among three groups: healthy volunteers, cases diagnosed as PTSD, and cases without PTSD. Among the 34 pair-matched cases and controls, IL-6 was significantly higher in both PTSD positive cases [2.43 (0.00-14.54) pg/ml; p = 0.004] and PTSD negative cases [3.00 (0.92-3.86) pg/ml; p = 0.005], than in controls [0.39 (0.00-11.38) pg/ml]. IL-1ß was significantly higher in PTSD positive cases [0.17 (0.00-5.27) pg/ml; p = 0.011] than in controls 0.00 (0.00-0.12) pg/ml. Other cytokines did not show significant differences. IL-6 was higher in both the trauma affected groups and IL-1ß was higher in the trauma affected group with PTSD when compared to healthy controls. This supports the immune system activation hypothesis after trauma.

Lung metastasis from renal cell carcinoma 16 years after nephrectomy: A case report and review of the literature.

Renal cell carcinoma can have lung metastasis even after a long interval of radical nephrectomy (16 years after nephrectomy in our case). If any pulmonary nodule is diagnosed with a history of RCC, pulmonary metastasis of RCC should be suspected and should be appropriately treated.

Mature ovarian teratoma with gliomatosis peritonei: A rare case report.

Gliomatosis peritonei (GP) is rarely observed along with mature ovarian teratoma. However, it is important to recognize the benign nature of GP when associated with mature ovarian teratoma. Treatment for primary tumor and long-term follow-up is vital.

Primary squamous cell carcinoma of the breast in a young female- A rare ailment.

Primary squamous cell carcinoma of the breast is an extremely rare invasive breast carcinoma with rapid progression and worse prognosis. Careful assessment and diagnosis of the entity should also be considered in a rapidly progressing breast tumor.

Malignant transformation of mature cystic teratoma into undifferentiated carcinoma: A case report.

Malignant transformation of mature cystic teratoma (MCTO) is a rare entity. Even rarer is the transformation of MCTO into undifferentiated carcinoma. We report a case of an 80-year-old woman with undifferentiated carcinoma and squamous cell carcinoma component originating from mature cystic teratoma of the ovary.

Trends and clinicopathological characteristics of oral squamous cell carcinomas reported at a tertiary cancer hospital in Nepal during 1999 to 2009.

OBJECTIVE: Reliable data describing the trends and clinicopathological characteristics of oral squamous cell carcinoma (OSCC) in the Nepalese population are very limited. The current study aimed to examine the demographics, trend, and clinicopathological characteristics of OSCC reported to the main referral/tertiary cancer hospital, the B.P. Koirala Memorial Cancer Hospital (BPKMCH) in Nepal for a period of 11 years (1999-2009). MATERIAL AND METHODS: This is a cross-sectional study. Data were retrieved retrospectively from hospital register maintained in the Department of Ear, Nose, Throat at BPKMCH, categorized into demographic and clinicopathological variables and SPSS (V25) was used for the analysis. RESULTS: In a period of 11 years, 3,452 cases of head and neck cancer were registered at the Department of Ear, Nose, Throat, BPKMCH. Out of 1,111 oral cancer cases, 1,081 (97.3%) were OSCC. A trend for increasing number of OSCCs presenting to BPKMCH was observed during that period. OSCC was found to be more common among males (73.0%), Brahmin/Chhetri ethnic groups (33.0%), in age group of 51-60 years (31.9%), and in Terai region (62.0%). Tongue (42.8%) was the most common site, followed by buccal mucosa (27.2%). Nevertheless, when stratified with respect to the geographical location and ethnicity, buccal mucosa was the most common site for OSCC in Terai region (63.9%, p = .002) and in Madhesi ethnic group (34.2%, p < .001). Majority of OSCC cases were diagnosed at advanced stage (49.7%, Stage IV) and received a combination therapy (42.0%). CONCLUSIONS: Hospital-based records can provide valuable information on disease characteristics in countries like Nepal. This study revealed that the clinicopathological characteristics of OSCC in Nepal follow the global trend. Nevertheless, relationship between specific intraoral sites for OSCC with geographic location and ethnic groups is an interesting observation and requires further population-based studies to clarify these findings.

Tumor Budding, EMT and Cancer Stem Cells in T1-2/N0 Oral Squamous Cell Carcinomas.

BACKGROUND: Early oral carcinomas have a high recurrence rate despite surgery with clear margins. In an attempt to classify the risk of recurrence of oral squamous cell carcinomas, we explored the significance of tumor budding, epithelial-mesenchymal transition (EMT) and certain cancer stem cell markers (CSC). MATERIALS AND METHODS: Tumor budding (single cells or clusters of ≤5 cells in the tumor front, divided into high- and low-budding tumors), EMT and CSC markers were studied in 62 immunohistochemically stained slides of T1/2N0M0 oral squamous cell carcinomas. Tissues and records of follow-up were obtained from the Oslo University Hospital, Norway. Tumor budding, EMT and CSC markers were scored and analyzed. RESULTS: The only significant prognostic marker was tumor budding (p=0.043). Expression of the EMT marker E-cadherin was lost from the invasive front and tended to be a prognostic factor (p=0.17), and up-regulation of vimentin in tumor cells in the invasive front was found; this indicates that EMT had occurred. CSC markers were not associated with recurrence rate in the present study. CONCLUSION: A high budding index was related to poor prognosis in patients with oral cancer. Budding was associated with EMT-like changes. CSC factors were detected but reflected differentiation rather than stemness. Scoring of buds in patients with oral cancer may help discriminate invasive tumors prone to relapse, and thus, provide an indication for adjuvant therapy.

The clinical impact of mean vessel size and solidity in breast carcinoma patients.

Angiogenesis quantification, through vessel counting or area estimation in the most vascular part of the tumour, has been found to be of prognostic value across a range of carcinomas, breast cancer included. We have applied computer image analysis to quantify vascular properties pertaining to size, shape and spatial distributions in photographed fields of CD34 stained sections. Aided by a pilot (98 cases), seven parameters were selected and validated on a separate set from 293 breast cancer patients. Two new prognostic markers were identified through continuous cox regression with endpoints breast cancer specific survival and distant disease free survival: The average size of the vessels as measured by their perimeter (p = 0.003 and 0.004, respectively), and the average complexity of the vessel shapes measured by their solidity (p = 0.004 and 0.004). The Hazard ratios for the corresponding median-dichotomized markers were 2.28 (p = 0.005) and 1.89 (p = 0.016) for the mean perimeter and 1.80 (p = 0.041) and 1.55 (p = 0.095) for the shape complexity. The markers were associated with poor histologic type, high grade, necrosis, HR negativity, inflammation, and p53 expression (vessel size only). Both markers were found to strongly influence the prognostic properties of vascular invasion (VI) and disseminated tumour cells in the bone marrow. The latter being prognostic only in cases with large vessels (p = 0.004 and 0.043) or low complexity (p = 0.018 and 0.024), but not in the small or complex vessel groups (p>0.47). VI was significant in all groups, but showed greater hazard ratios for small and low complexity vessels (6.54-11.2) versus large and high complexity vessels (2.64-3.06). We find that not only the overall amount of produced vasculature in angiogenic hot-spots is of prognostic significance, but also the morphological appearance of the generated vessels, i.e. the size and shape of vessels in the studied hot spots.

Primary tumor vascularity, HIF-1α and VEGF expression in vulvar squamous cell carcinomas: their relationships with clinicopathological characteristics and prognostic impact.

BACKGROUND: Increased vascularity is a crucial event in the tumor progression and has prognostic significance in various cancers. However, the ultimate role of angiogenesis in the pathogenesis and clinical outcome of vulvar carcinoma patients is still not settled. METHODS: Tumor vascularity using CD34 stained slides measured by Chalkley counting method as well as hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) immunoexpression was examined in 158 vulvar squamous cell carcinomas. Associations between vascular Chalkley count, HIF-1α and VEGF expression and clinicopathological factors and clinical outcome were evaluated. RESULTS: High CD34 Chalkley count was found to correlate with larger tumor diameter (P = 0.002), deep invasion (P < 0.001) and HIF-1α (P = 0.04), whereas high VEGF expression correlate significantly with poor tumor differentiation (P = 0.007). No significant association between CD34 Chalkley counts and VEGF expression and disease-specific survival was observed. High HIF-1α expression showed better disease specific survival in both univariate and multivariate analyses (P = 0.001). CONCLUSIONS: A significant association between high tumor vascularity and larger tumor size as well as deeper tumor invasion suggests an important role of angiogenesis in the growth and progression of vulvar carcinomas. HIF-1α expression in vulvar carcinomas was a statistically independent prognostic factor.

Primary tumor vascularity in esophagus cancer. CD34 and HIF1-α expression correlate with tumor progression.

OBJECTIVE: Hypoxia inducible factor α (HIF1-α) is a key protein regulating the response of a variety of genes and pathways, including angiogenesis, to hypoxic stimuli. High vascularity in various carcinomas correlates with invasion and metastasis. Assessment of primary tumor vascularity and HIF1-α expression in esophageal carcinomas was an objective of this study. METHODS: The vascularity in esophageal carcinomas (n=52) was quantified by Chalkley method on CD34 immunostained sections. HIF1-α expression was examined by immunohistochemistry. The relationships between CD34 Chalkley count, HIF1-α and various clinico-pathological characteristics with clinical outcome were evaluated. RESULTS: High HIF1-α expression in squamous cell carcinoma (SCC) was significantly associated with the T3-4 group (p=0.02). A higher percentage of SCC with high HIF1-α expression compared to its expression in adenocarcinoma (AC) (p=0.005) was observed. In the SCC group, high CD34 Chalkley count and high HIF1-α expression implied a significantly reduced survival (p=0.003 and p=0.001). No such significant association was found in the AC group. CONCLUSIONS: HIF1-α expression is different in two separate tumor microenvironments: SCCs and ACs of the esophagus. This suggests that different mechanisms may be involved in HIF1-α expression- and activity between the two histological types of esophageal carcinoma.

Expression of cyclooxygenase-2 in invasive breast carcinomas and its prognostic impact.

Representative tumour sections from 468 patients with invasive breast cancer were immunostained for cyclooxygenase-2 (COX-2) and evaluated. The relationships between COX-2 expression, clinical outcome and various clinicopathological variables, including tumour vascularity and disseminated tumour cells (DTC) in the bone marrow were examined. COX-2 expression in invasive breast carcinoma cells was positively associated with oestrogen receptor and/or progesterone receptor positivity (p<0.001). Triple-negative tumours showed no/low COX-2 expression more frequently than other tumour types (p<0.001). Expression of COX-2 was not associated with breast cancer-specific survival (p=0.49, log-rank) or distant disease-free survival (p=0.67, log-rank) for all patients, including lymph node-negative, untreated patients (p>0.14, log-rank). There was also no significant association between COX-2 expression and histological grade, tumour size, nodal status, DTC in bone marrow, p53, HER2, or tumour vascularity. In conclusion, COX-2 expression in this series was associated with the presence of hormone receptors. Low COX-2 expression was observed in triple-negative breast carcinomas.

Expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2 in invasive breast carcinoma: prognostic significance and relationship with markers for aggressiveness.

AIMS: Vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR-1) and VEGF receptor 2 (VEGFR-2) play a role in breast cancer growth and angiogenesis. We examined the expression and relationship with clinical outcome and other prognostic factors. METHODS AND RESULTS: Tumour sections from 468 breast cancer patients were immunostained for VEGF, VEGFR-1, and VEGFR-2, and their relationships with tumour vascularity, disseminated tumour cells (DTCs) in bone marrow and other clinicopathological parameters were evaluated. VEGF, VEGFR-1 and VEGFR-2 immunoreactivities were observed in invasive breast carcinoma cells. VEGF expression was significantly associated with VEGFR-1 and VEGFR-2 expression (P < 0.001). High-level cytoplasmic expression of VEGFR-1 was associated with significantly reduced distant disease-free survival (DDFS) (P = 0.017, log-rank) and breast cancer-specific survival (BCSS) (P = 0.005, log-rank) for all patients, and for node-negative patients without systemic treatment (DDFS, P = 0.03, log-rank; BCSS, P = 0.009, log-rank). VEGFR-1 expression was significantly associated with histopathological markers of aggressiveness (P < 0.05). Significantly reduced survival was observed in DTC-positive patients as compared with DTC-negative patients in the combined moderate/high VEGFR-1 group (P < 0.001 for DDFS and BCSS), and the same was true for DDFS in the moderate VEGFR-2 group (P = 0.006). CONCLUSIONS: High-level expression of VEGFR-1 indicates reduced survival. Higher-level expression of VEGFR-1 or VEGFR-2 in primary breast carcinomas combined with the presence of DTC selects a prognostically unfavourable patient group.

Quantification of angiogenesis in breast cancer by automated vessel identification in CD34 immunohistochemical sections.

BACKGROUND/AIM: Tumor growth is dependent upon angiogenesis. Tumor vascularity, as measured by microvessel density or Chalkley counts, has been shown to predict treatment outcome. However, many issues related to reproducibility and methodology have prevented its clinical application. We present a method of automatic vessel identification applied to CD34 immunohistochemical sections which facilitates increased reproducibility. MATERIALS AND METHODS: Pixel colour information was used to identify CD34 stain. In order to reduce the effects of noise and background, stained areas smaller than 3.5 µm were ignored. RESULTS: Comparing automatic and manual vessel counts in 50 randomly selected breast cancer cases, the method achieved an intraclass correlation coefficient of r(a)(2)=0.96 and a 95% confidence interval for the percentage difference between the counts from -26.1% to 10.8%. The method was also found to have a sensitivity approaching 100%. CONCLUSION: The method can reliably be used on colour photographs of staining for CD34 to quantify angiogenesis.

Breast carcinoma vascularity: a comparison of manual microvessel count and Chalkley count.

Manual counting of microvessels as intratumoral microvessel density (MVD) and Chalkley counting have been used in several studies to assess the prognostic impact of vascularity in invasive breast carcinomas. In our present study, the aim was to evaluate the prognostic value of angiogenesis in invasive breast carcinoma assessed by MVD and Chalkley techniques in the same series of patients. A total of 498 breast carcinoma patients with median follow up time 85 months were evaluated. The tumour vascularity was quantified by both manual microvessel count (MVD) and Chalkley count in CD34 stained breast carcinoma slides by a single investigator blinded to clinical information. Other relevant clinicopathological parameters were noted, including breast cancer related death and both loco-regional and systemic relapse. The patients were stratified by converting MVD and Chalkley counts to categorical variables to assess prognostic impact, and results were compared. High vascular grades using MVD count did not demonstrate any prognostic significance for breast cancer specific survival (BCSS) or distant disease free survival (DDFS) either in whole patient group (BCSS, p=0.517, DDFS, p=0.301) or in non-treated node negative patients (p>0.05). Chalkley count showed prognostic significance for both DDFS and BCSS in whole patient group (p<0.001) and also in untreated node negative patient group (p<0.05). In multivariate analysis, Chalkley count, but not MVD, retained the prognostic value for BCSS (p=0.007) and DDFS (p=0.014). The Chalkley count for assessing angiogenesis in invasive breast carcinomas demonstrated prognostic value. The Chalkley method appears to be the better method in estimating the prognostic impact of vascularity in invasive breast carcinomas.

Vascularization in primary breast carcinomas: its prognostic significance and relationship with tumor cell dissemination.

PURPOSE: The interaction between tumor cells, stroma, and endothelial cells is important for the dissemination of tumor cells. The aim of the present study is to examine vascularity in primary breast carcinomas and its prognostic significance and relationship with tumor cell dissemination. EXPERIMENTAL DESIGN: A total of 498 invasive breast carcinomas were analyzed. Representative tumor sections were stained for CD34 and CD105, and vascularity was quantified by the Chalkley method. The relationship between Chalkley counts, vascular invasion, disseminated tumor cells (DTC) in the bone marrow, other clinicopathologic variables, and clinical outcome was evaluated. RESULTS: High vascular grades determined by Chalkley counts were significantly associated with shorter distant disease-free survival and breast cancer-specific survival in all patients (P < 0.001, log-rank) and in node-negative patients not receiving adjuvant systemic therapy (P < 0.05). In multivariate analysis, both CD34 and CD105 Chalkley counts showed prognostic significance for distant disease-free survival (P = 0.014 and P = 0.026), whereas CD34 also showed prognostic significance for breast cancer-specific survival (P = 0.007). Vascular invasion and DTCs in the bone marrow showed independent prognostic significance. DTC did not discriminate survival for CD34 low Chalkley counts, whereas a very poor prognosis was observed for DTC-positive patients with high CD34 counts. In node-negative patients not receiving systemic chemotherapy, high CD34 and high CD105 counts in combination identified patients with unfavorable outcome, as opposed to all other CD34/CD105 combinations. CONCLUSIONS: Improved identification of risk groups could be obtained by adding CD34 and CD105 vascular analysis to DTC, vascular invasion, and other primary tumor factors. This may facilitate the selection of candidates for adjuvant systemic therapy.

Initial experience in a cancer hospital in Nepal with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer.

To evaluate the performance and feasibility of sentinel lymph node biopsy in early breast cancer patients using patent blue dye. From March 2004, we are consecutively enrolling breast cancer patients with tumor size less than 5 cm with no clinically palpable axillary lymph nodes in this feasibility study. So far, 21 patients underwent sentinel lymph node biopsy using 1.0% patent blue dye injection around the tumor followed by axillary dissection. Sentinel lymph node biopsy was compared with axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes. Age of patients ranged form 32-67 years old with mean age of 46.72 years. Fifty seven percent of patients were postmenopausal. Patients with T1 lesions were 8 and T2 were 13. The sentinel lymph node/s were successfully identified in 20 out of 21 patients (95.0%). The number of sentinel lymph nodes ranged from 1 to 5 (average 2.0) and non-sentinel nodes ranged from 5-22 (average 12.0). Infiltrating ductal carcinoma was diagnosed in 15 patients, DCIS with early invasion in 4 patients, invasive lobular carcinoma in 1 and medullary carcinoma in 1 patient. Of the 20 patients in whom sentinel lymph nodes were successfully identified, nodes were positive in 35.0% (7/20) of patients. All the positive nodes were detected in group with T2 lesions. SLNs were the only positive nodes in 2 patients. There were no false negative patients, yielding an accuracy of 100.0%. Lymphatic mapping using patent blue dye alone is technically feasible for patients with small (T1 or T2) palpable breast tumors. The sentinel node can be reliably identified in the majority of these patients, and its histology reflects that of the axilla with a high degree of accuracy. This method is very useful in economically backward countries as it involves less expensive material.

Ganglioneuroma of pelvis--an unique presentation in a young man.

Ganglioneuromas presented as a pelvic tumor around the pelvic organs is a rare entity. A case with unusual presentation is reported. Young man of 18 years old presented with a complaint of lower abdominal mass increasing in size for last 3 years. It was treated with partial resection for debulking purpose after the conformation during surgery with frozen section. Debulking surgery with preservation of organ functions is feasible in these slow growing tumors for better quality of life.