Evaluation of Sentinel Lymph Node Status and its Association with Clinicopathological Factors in Patients with Cutaneous Melanoma: A Retrospective Study

Background: Cutaneous Melanoma (CM) is cancer with rising prevalence worldwide. The most significant predictor of CM is regional lymph node metastasis. Sentinel Lymph Node (SLN) biopsy has been used to stage CM and to identify lymphatic metastasis. This study aims to evaluate the SLN association with clinicopathological factors in the CM patients for a better surgical management. Methods: This retrospective study included 80 CM patients who had gone through lymphatic mapping and SLN biopsy at Imam Khomeini Hospital in Tehran from 2011 to 2018. The clinical and histologic factors, including sex, age, tumor location, Breslow thickness, ulceration, angiolymphatic invasion, tumor mitotic rate (TMR), and Clark level, were analyzed.Results: Fifty-six patients (70%) were found to have SLN, 19 patients (33.9%) were SLN-positive, and 37 patients (66.1%) were SLN-negative. Breslow thickness was the only variable that was significantly associated with the prediction of SLN. SLN was not correlated with other features such as ulceration, angiolymphatic invasion, and tumor mitotic rate. Complete Lymph Node Dissection (CLND) was carried out in 18 out of 19 SLN-positive patients. Moreover, 5 patients (27.8%) were found to be non-SLN-positive out of 18 SLN biopsy+CLND-positive patients. Furthermore, there was not any significant relationship between the clinicopathological features and the prediction of non-SLN. Conclusions: Breslow thickness was significantly correlated with positive SLN biopsy. Thus, it can be a strong predictor of positive SLN in CM patients.

Immunopositivity for Siglec-15 in gastric cancer and its association with clinical and pathological parameters

The sialic acid-binding immunoglobulin-type lectin Siglec-15 is a promising target to cancer immunotherapy in several tumor types. The present study aimed to investigate Siglec-15 expression in gastric cancer (GC) patient tissue and to evaluate its clinical value. Siglec-15 expression was evaluated by immunohistochemistry with 71 patients. Siglec-15 staining was observed in tumor cells of 53 (74.64%) patients, with significant association with histologic classification and angiolymphatic invasion (p<0.05). Immunohistochemistry analysis also detected Siglec-15 in tumor-associated stroma cells (macrophages/myeloid cells). There was no significant association with outcomes parameters. Siglec-15 expression in well differentiated histological GC tissues and in the tumor microenvironment are potential targets to be further investigated as a novel prognostic factor for GC.

Comparison of clinicopathologic parameters and oncologic outcomes between type 1 and type 2 papillary renal cell carcinoma

Background To compare the clinicopathologic parameters and oncologic outcomes between type 1 and type 2 papillary renal cell carcinoma (PRCC). Methods This study was approved by the review board (NO.XYFY2019-KL032–01). Between 2007 and 2018, 52 consecutive patients who underwent surgery at a single tertiary referral hospital were included. Clinicopathologic and survival data were collected and entered into a database. The Kaplan-Meier method, and univariate and multivariate Cox proportional hazard regression analyses were performed to estimate progression-free survival (PFS) and cancer-specific survival (CSS). Results Of the 52 patients, 24 (46.2%) were diagnosed with type 1 PRCC, and 28 (53.8%) had type 2 PRCC. The mean tumor size was 4.8 ± 2.5 cm. The two subtypes displayed different morphological features: foamy macrophages were more common in type 1 PRCC, while eosinophils and microvascular angiolymphatic invasion were more frequent in type 2 PRCC. Type 2 cases showed higher tumor stage and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade than type 1 cases (T3-T4: 43% vs 17%, P = 0.041; G3-G4: 43% vs 8%, P = 0.005). In univariate analysis, type 2 PRCC had a lower probability for PFS and CSS than patients with type 1 PRCC (P = 0.016, P = 0.049, log-rank test, respectively). In multivariate analysis, only WHO/ISUP grade (HR 11.289, 95% CI 2.303–55.329, P = 0.003) and tumor size (HR 1.244, 95% CI 1.034–1.496, P = 0.021) were significantly associated with PFS. Conclusions PRCC subtype displayed different morphological features: foamy macrophages, eosinophils and microvascular angiolymphatic invasion are pathologic features that may aid in the distinction of the two subtypes. Histologic subtype of PRCC is not an independent prognostic factor and only WHO/ISUP grade and tumor size were independent predictors for PFS.

Risk factors and treatment outcomes of 239 patients with testicular granulosa cell tumors: a systematic review of published case series data

Purpose Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes. Methods We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level. Results From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission. Conclusion Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

Discoidin Domain Receptor-1 (DDR1) is Involved in Angiolymphatic Invasion in Oral Cancer

The discoidin domain receptor-1 (DDR1) is a non-integrin collagen receptor recently implicated in the collective cell migration of other cancer types. Previously, we identified an elevated expression of DDR1 in oral squamous cell carcinoma (OSCC) cells. Through the data mining of a microarray dataset composed of matched tumor-normal tissues from forty OSCC patients, we distilled overexpressed genes statistically associated with angiolymphatic invasion, including DDR1, COL4A5, COL4A6 and PDPN. Dual immunohistochemical staining further confirmed the spatial locations of DDR1 and PDPN in OSCC tissues indicative of collective cancer cell invasion. An elevated DDR1 expression at both the transcription and protein level was observed by treating keratinocytes with collagen of fibrillar or basement membrane types. In addition, inhibition of DDR1 kinase activity in OSCC TW2.6 cells disrupted cell cohesiveness in a 2D culture, reduced spheroid invasion in a collagen gel matrix, and suppressed angiolymphatic invasion in xenograft tissues. Taken together, these results suggest that collagen deposition in the affected tissues followed by DDR1 overexpression could be central to OSCC tumor growth and angiolymphatic invasion. Thus, DDR1 inhibitors are potential therapeutic compounds in restraining oral cancer, which has not been previously explored.

Sentinel Lymph Node Biopsy in Head and Neck Melanoma: Long-term Outcomes, Prognostic Value, Accuracy, and Safety

Objective To evaluate the long-term outcomes of sentinel lymph node biopsy (SLNB) for head and neck cutaneous melanoma (HNCM). Study Design Retrospective cohort study. Setting Tertiary academic medical center. Subjects and Methods Longitudinal review of a 356-patient cohort with HNCM undergoing SLNB from 1997 to 2007. Results Descriptive characteristics included the following: age, 53.5 ± 19 years (mean ± SD); sex, 26.8% female; median follow-up, 4.9 years; and Breslow depth, 2.52 ± 1.87 mm. Overall, 75 (21.1%) patients had a positive SLNB. Among patients undergoing completion lymph node dissection following positive SLNB, 20 (27.4%) had at least 1 additional positive nonsentinel lymph node. Eighteen patients with local control and negative SLNB developed regional disease, indicating a false omission rate of 6.4%, including 10 recurrences in previously unsampled basins. Ten-year overall survival (OS) and melanoma-specific survival (MSS) were significantly greater in the negative sentinel lymph node (SLN) cohort (OS, 61% [95% CI, 0.549-0.677]; MSS, 81.9% [95% CI, 0.769-0.873]) than the positive SLN cohort (OS, 31% [95% CI, 0.162-0.677]; MSS, 60.3% [95% CI, 0.464-0.785]) and positive SLN/positive nonsentinel lymph node cohort (OS, 8.4% [95% CI, 0.015-0.474]; MSS, 9.6% [95% CI, 0.017-0.536]). OS was significantly associated with SLN positivity (hazard ratio [HR], 2.39; P < .01), immunosuppression (HR, 2.37; P < .01), angiolymphatic invasion (HR, 1.91; P < .01), and ulceration (HR, 1.86; P < .01). SLN positivity (HR, 3.13; P < .01), angiolymphatic invasion (HR, 3.19; P < .01), and number of mitoses ( P = .0002) were significantly associated with MSS. Immunosuppression (HR, 3.01; P < .01) and SLN status (HR, 2.84; P < .01) were associated with recurrence-free survival, and immunosuppression was the only factor significantly associated with regional recurrence (HR, 6.59; P < .01). Conclusions Long-term follow up indicates that SLNB showcases durable accuracy, safety, and prognostic importance for cutaneous HNCM.