Subsequent Node Metastasis Research Articles

Uterine tumors mimicking ovarian sex cord tumors with rhabdoid differentiation: a clinicopathologic study of 4 cases: A case series analysis.

Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with rhabdoid features are uncommon mesenchymal neoplasms exhibiting diverse histological patterns, including significant rhabdoid morphology. A thorough comprehension of their clinicopathologic features is crucial for precise diagnosis and effective management. This study presents 4 cases of UTROSCT with rhabdoid features, diagnosed in patients aged 31 to 58. Varied recurrence patterns were observed, including similar recurrent lesions to the primary tumors with subsequent mortality, initial invasion and lymph node metastasis, and presence of only primary tumor. Histopathological examination revealed diverse morphological patterns, prominently featuring rhabdoid differentiation. Immunohistochemical analysis showed expression of hormone receptors, sex cord, smooth muscle, and epithelial markers, notably WT1, CD56, and CD99. Molecular analysis identified ESR1-NCOA2 fusions and ESR1 and NCOA2/3 rearrangements, indicating a potential association between these genetic alterations and extensive rhabdoid differentiation. Various treatments were administered post-recurrence, including chemotherapy and targeted therapies. However, poor clinical outcomes were observed in all cases. Despite aggressive treatments, including chemotherapy and targeted therapies, poor clinical outcomes were observed, highlighting the aggressive nature of UTROSCT with significant rhabdoid differentiation. This case series emphasizes the importance of detailed pathological reporting, comprehensive molecular testing, and thorough tumor staging in UTROSCT cases with rhabdoid features. Enhanced understanding of the clinicopathologic characteristics of UTROSCT with rhabdoid differentiation is crucial for accurate diagnosis, prognostication, and management strategies.

DHCR7 promotes lymph node metastasis in cervical cancer through cholesterol reprogramming-mediated activation of the KANK4/PI3K/AKT axis and VEGF-C secretion

Cervical cancer (CC) patients with lymph node metastasis (LNM) have a poor prognosis. However, the molecular mechanism of LNM in CC is unclear, and there is no effective clinical treatment. Here, we found that 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the last step of cholesterol synthesis, was upregulated in CC and closely related to LNM. Gain-of-function and loss-of-function experiments proved that DHCR7 promoted the invasion ability of CC cells and lymphangiogenesis in vitro and induced LNM in vivo. The LNM-promoting effect of DHCR7 was partly mediated by upregulating KN motif and ankyrin repeat domains 4 (KANK4) expression and subsequently activating the PI3K/AKT signaling pathway. Alternatively, DHCR7 promoted the secretion of vascular endothelial growth factor-C (VEGF-C), and thereby lymphangiogenesis. Interestingly, cholesterol reprogramming was needed for the DHCR7-mediated promotion of activation of the KANK4/PI3K/AKT axis, VEGF-C secretion, and subsequent LNM. Importantly, treatment with the DHCR7 inhibitors AY9944 and tamoxifen (TAM) significantly inhibited LNM of CC, suggesting the clinical application potential of DHCR7 inhibitors in CC. Collectively, our results uncover a novel molecular mechanism of LNM in CC and identify DHCR7 as a new potential therapeutic target.

The Interrelation Among Triad of Depth of Invasion, Perineural Invasion and Tumor Size in Squamous Cell Carcinoma of Tongue and Floor of the Mouth: An Analytical Appraisal.

Head and neck cancer represents 5-10% of all malignancies. Squamous cell carcinoma (SCC) of the oral cavity represents about 2% of overall malignant neoplasms and 47% of the head and neck region. Squamous cell carcinoma of tongue has a peculiar behavior of occult and skips metastasis to regional lymph nodes. It occasionally occurs along with floor of the mouth. The purpose of this study is to evaluate the significance of correlation between, depth of invasion of the primary tumor, its proximity with the neurovascular bundle and subsequent perineural invasion and cervical lymph node metastasis in squamous cell carcinoma tongue and floor of the mouth and the sites involving both. A total of 108 patients with carcinoma tongue (59), floor of the mouth (20) and involving both together (29) who underwent treatment during January 2015 to June 2017 that were followed up until December 2019 were assessed. Out of 108 patients that were included in the study, 71 patients underwent primary surgery and 37 patients were inoperable (tongue-17, floor of the mouth-9 and involving both together-11). Perineural invasion was seen in 15 cases of pT1-2 where depth of invasion was less than 1cm and in 28 cases of pT3-4 where depth of invasion was more than 1cm (p-0.075). Skip metastasis was accounted for 61.9% overall. The triad of perineural invasion, depth of invasion and tumor size is interrelated and was responsible for cervical lymph node metastasis and prognosis of the disease. Obtaining clear deep margins of the tumor from the mucosal margin and removal of lympho-fatty tissue at the floor of the mouth is an important aspect which gives the indication about prognostic factors like depth of invasion, tumor size, cervical nodal metastasis and recurrence of the disease. High-grade tumors (T3-4), depth of invasion of tumor at 1cm or > 1cm, increase the propensity of perineural invasion highly.

Clinical effects of cervical conization with positive margins in cervical cancer

Radical surgery after cervical conization is a common approach for the treatment of cervical cancer. In some cases, disease progression is observed after positive margins at conization, but the effect of conization on disease progression remains unclear. Thus, the aim of this study was to investigate the clinical outcomes of positive margins at conization in cervical cancer. A total of 101 patients who underwent cervical conization before radical hysterectomy and pelvic lymph node dissection were considered eligible by reviewing medical records. The association between the positive margins and patient outcomes, including subsequent lymph node metastasis, was evaluated. The rate of lymphovascular space invasion (LVSI) positivity at radical surgery was significantly higher in patients with positive margins (p = 0.017) than in those with negative margins, although there was no significant difference in the rate of pelvic lymph node metastasis (p = 0.155). Moreover, there was no significant difference in the overall survival or progression-free survival between the two groups (p = 0.332 and 0.200, respectively). A positive margin at conization presented no significant prognostic disadvantage; thus, diagnostic conization is one of the most suitable treatment options for early-stage cervical cancer that is difficult to accurately assess.

A Case of Colonic Endocrine Cell Carcinoma with Subsequent Axillary Lymph Node Metastasis of which Resection Led to a Long-term Survival

A Case of Colonic Endocrine Cell Carcinoma with Subsequent Axillary Lymph Node Metastasis of which Resection Led to a Long-term Survival

Vascular endothelial growth factors C and D and lymphangiogenesis at the early stage of esophageal squamous cell carcinoma progression.

We conducted a detailed study of lymphangiogenesis and subsequent lymph node metastasis in early-stage esophageal squamous cell carcinoma (ESCC) using immunostaining for D2-40 and vascular endothelial growth factor (VEGF)-C and D. The study materials included 13 samples of normal squamous epithelium, 6 samples of low-grade intraepithelial neoplasia (LGIN), and 60 samples of superficial ESCC (M1 and M2 cancer 24; M3 or deeper cancer 36). We assessed lymphatic vessel density (LVD) using D2-40 and immunoreactivity for VEGF-C and D in relation to histological type, lymphatic invasion, and lymph node metastasis. LVD in M1 and M2 lesions and M3 or deeper lesions was significantly higher than in normal squamous epithelium (P<0.001). High expression of VEGF-C and D was observed in M1 and M2 cancer and in M3 or deeper cancer, but not in normal squamous epithelium or LGIN. LVD in VEGF-C- and D-positive cases was significantly higher than in negative cases (P<0.001). In M3 or deeper cancer, the correlation between VEGF-C or D status and lymphatic invasion or lymph node metastasis was not significant. LVD in cases with positive lymphatic invasion and those with lymph node metastasis was significantly higher than in cases lacking either (P=0.02 and 0.03, respectively). ESCC cells produce VEGF-C and D from the very early stage of progression. VEGF-C and D activate lymphangiogenesis, and this increase of lymphatic vessels leads to lymphatic invasion and subsequent lymph node metastasis.

The relationship between primary tumour thicknesses in cancers of the oral cavity to subsequent lymph node metastasis

Background: Elective dissection of cervical lymph nodes in oral cavity cancers gives very precious data on its pathological state, judge for adjuvant therapy requirement plus its therapeutic effect but it has its morbidities that cannot be condoned. Tumor thickness (TT) in oral cavity cancers show an increasing value to be one of the most important and reliable factors that have a great relationship to regional node involvement.Methods: Forty-three patients with T1, T2 oral cavity squamous cell carcinoma with clinically and radiologically negative cervical L.Ns underwent elective neck dissection and the relation between the tumor thickness and the nodal metastasis was monitored. Tumor thickness was estimated preoperatively by using the intra-oral ultrasound and confirmed by histopathology postoperatively.Results: Only 12 out of 43 neck dissections (27.9%) showed positive L.Ns metastasis of primary tumor. The excised number of L.Ns ranged from 15 to 31 with mean±SD (21.58±3.59) L.Ns. The (TT) ranged from 1.4 mm to 7.8 mm. Our statistical results showed that there is a cutoff point which was 4 mm where (TT) &gt; 4 mm showed significant results with histologically found positive cervical node metastasis compared to (TT) ≤4 mm specimens.Conclusions: Relationship of tumor thickness to lymph node metastasis was found to be significant as shown by this study. Our results clearly demonstrate that conservative elective neck dissection is indicated in patients with stage I/II oral cavity carcinoma whose tumors are &gt; 4 mm in thickness as they mostly have latent metastasis.

Clinicopathological implications to micropapillary bladder urothelial carcinoma of the presence of sialyl Lewis X-decorated mucin 1 in stroma-facing membranes

ObjectivesBladder urothelial carcinoma (UC) comprises more than 90% of all bladder cancers. Among several UC variants, micropapillary UC (MPUC) is a rare one with high potential for lymphovascular invasion and subsequent lymph node metastasis. Histologically, MPUC is characterized by the presence of small papillary carcinoma cell clusters surrounded by lacunar spaces. Immunohistochemically, the outer circumference of these clusters, that is, the stroma-facing membrane of carcinoma cells, is reportedly almost invariably positive for mucin 1 (MUC1) protein and to a lesser extent for sialyl Lewis X (sLeX) carbohydrates; however, the clinicopathological implications of these expression patterns have not been fully investigated. Materials and methodsWe performed immunohistochemical analysis of MPUC (n = 11) and conventional UC (n = 57) for MUC1 and sLeX to determine whether these factors immunolocalized. Dual immunofluorescence staining was also carried out to assess MUC1 and sLeX colocalization. We also performed Western blot analysis of Chinese hamster ovary cells misexpressing both recombinant epitope-tagged MUC1 and glycosyltransferases enabling sLeX biosynthesis. ResultsMPUC samples preferentially exhibited both MUC1 protein and sLeX carbohydrate expression on the stroma-facing membrane of carcinoma cells. Based on univariate analysis, MUC1 expression in that pattern was positively correlated with tumor extension, lymphovascular invasion, lymph node metastasis, disease stage, and relatively poor patient prognosis. A comparable sLeX expression pattern also correlated positively with tumor extension and nodal metastasis. Based on multivariate analysis, localization of MUC1 and sLeX on the stroma-facing side of the membrane was positively correlated with lymph node metastasis. ConclusionsOverall, our immunofluorescence findings as well as immunoprecipitation analyses of Chinese hamster ovary cell transfectants strongly suggest that MUC1 is a potential scaffold protein for sLeX carbohydrates in MPUC. Both MUC1 and sLeX may cooperatively contribute to MPUC histogenesis and clinicopathological characteristics.

Tumor necrosis predicts poor clinical outcomes in patients with node-negative upper urinary tract urothelial carcinoma.

Tumor necrosis has been indicated as a factor for the poor clinical outcome in human cancers. We aim to disclose the association between tumor necrosis and overall survival and recurrence-free survival in node-negative upper urinary tract urothelial carcinoma patients treated with radical nephroureterectomy. A retrospective cohort of 100 patients with upper urinary tract urothelial carcinoma from January 1990 to June 2011 was enrolled in this study. Univariate analysis with Log-rank test and multivariate analysis with Cox proportional hazards regression models were conducted to determine the correlations of tumor necrosis with overall survival and recurrence-free survival. Tumor necrosis was presented in 48 patients with upper urinary tract urothelial carcinoma and was significantly associated with the advanced pathological stage (P < 0.001), high tumor grade (P < 0.001), subsequent bladder tumor (P = 0.018), vascular invasion (P < 0.001) and lymph node metastasis (P = 0.026). Multivariate analysis revealed tumor necrosis as an independent unfavorable predictor of overall survival in node-negative upper urinary tract urothelial carcinoma patients by multivariate analysis (hazard ratio = 9.23, 95% confidence interval = 1.05-80.89, P = 0.045). Tumor necrosis was an independent factor of adverse clinical outcomes in node-negative upper urinary tract urothelial carcinoma patients who received radical nephroureterectomy. Evaluation of tumor necrosis might be of clinical significance to determine whether patients with node-negative upper urinary tract urothelial carcinoma should be given further therapy after radical nephroureterectomy.

Abstract 4950: Defective expression of partition-defective 3 (PAR-3) is associated with adverse prognostic factors in esophageal squamous cell carcinoma

Abstract Esophageal cancer is the sixth leading cause of cancer mortality and squamous cell carcinoma is a prevalent histological subtype worldwide. The partition-defective 3 (PAR-3) protein belongs to a partition defective complex that controls polarity, which is mainly composed of PAR-3, PAR-6, and atypical protein kinase C (aPKC). PAR-3 contains one self-oligomerization domain in the N-terminus, three PDZ protein interaction domains and one aPKC-binding domain. Owing to these domains, PAR-3 is able to form a conserved protein complex with PAR-6 and aPKC. In mammalian epithelial cells, PAR complex assembles at tight junctions, and plays a role in controlling apical-basal polarity, asymmetric cell division, and directional cell migration. It is well known that disrupted cell polarity is a feature of epithelial cancers. Therefore, it is believed that PAR proteins may be involved in multiple aspects of oncogenesis and tumor-promoting function. We previously detected a homozygous deletion of PAR-3 gene in esophageal squamous cell carcinoma (ESCC) cell lines by a high-density oligonucleotide microarray approach. (Oncogene 28:2910-2918, 2009). A copy number loss of PAR-3 gene was observed in 15% of primary ESCC tumors. The expression of PAR-3 mRNA was significantly reduced in 70% of ESCC tumors when compared with their nontumorous tissue counterparts. Exogenous expression of PAR-3 gene in ESCC cells lacking this gene (KYSE30 cells) enhanced the recruitment of Zonula occludens 1 (ZO-1), a marker of tight junctions, to sites of cell-cell contact. Conversely, knockdown of PAR-3 gene in ESCC cells expressing this gene disrupted ZO-1 localization at cell-cell borders. Although our previous findings suggested that deletion and reduced expression of PAR-3 gene may be a novel mechanism that drives the progression of ESCC, the clinical relevance of PAR-3 in ESCC tumor progression was not known. In the present study, we aimed to investigate the expression pattern of PAR-3 protein in primary ESCC tumors and to clarify any potential relationship between the PAR-3 expression and clinicopathological parameters. Immunohistochemical analyses showed that PAR-3 protein was expressed at the basal layer of the normal squamous epithelium of the esophagus, esophageal glands proper and the duct of esophageal glands. Both normal esophageal cells and ESCC tumor cells showed granular cytoplasmic staining and particularly strong membranous staining of PAR-3 protein. PAR-3 protein expression was lost in 20 (37%) of 74 primary ESCC tumors. Loss of PAR-3 protein expression was significantly associated with invasion depth (P = 0.0065) and lymph node metastasis (P = 0.03). Our results suggest that loss of PAR-3 protein expression may lead to tumor progression and subsequent lymph node metastasis in ESCC. Citation Format: Tomoko Kitaichi, Koichiroh Yasui, Akira Tomie, Yasuyuki Gen, Osamu Dohi, Yuji Naito, Yoshito Itoh. Defective expression of partition-defective 3 (PAR-3) is associated with adverse prognostic factors in esophageal squamous cell carcinoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4950. doi:10.1158/1538-7445.AM2015-4950

The potential risk of vessel infiltration and cervical lymph node metastasis in hypopharyngeal superficial squamous cell carcinoma: a retrospective observational study

Conclusion: The depth of hypopharyngeal superficial cancer may predict vessel infiltration and potential risk of cervical lymph node metastasis. Objectives: To elucidate the histopathological predictors of vessel infiltration and the risk of regional lymph node metastasis in hypopharyngeal superficial cancer. Methods: This study included 31 lesions from 30 patients who had undergone transoral en bloc resection in the hospital. Patients with intraepithelial neoplasia or muscular invasion were excluded. Patient characteristics, nodal status, state of vessel infiltration, state of perineural invasion, histopathological parameters, and post-operative cervical lymph node recurrence were retrospectively examined. The histopathological parameters measured were tumor diameter and the following three parameters: tumor thickness, depth from the mucosal surface, and depth from the basement membrane. Correlations between histopathological parameters and state of vessel infiltration were statistically analyzed. Results: Of the 31 lesions examined, four had vessel infiltration. Three of the four lesions with vessel infiltration had regional lymph node metastasis as well as subsequent lymph node metastasis. Lesions with vessel infiltration were significantly deeper than those without. In contrast, there was no significant difference in lesion diameters. In addition, there was no correlation between the depth and the diameter of the lesion.

A Pediatric Case of Spitzoid Melanoma with Subsequent Large Lymph Node Metastasis.

Dear Editor: The lack of reliable pathological criteria for distinguishing between benign and malignant melanocytic lesions makes it very difficult for clinicians and pathologists to diagnosis melanoma. Here, we describe a rare case of a young patient affected by Spitzoid melanoma of the left leg with left superficial inguinal lymph node metastasis. A 13-year-old boy was referred to our hospital for a 19×9-mm cutaneous dome-shaped pigmented nodule on his left lower leg (Fig. 1A). The nodule appeared 3 months prior and was asymptomatic. No lymphadenopathy was found on physical examination. Under the suspicion of Spitz nevus, the tumor was excised with a 2-mm free margin. Histological analysis demonstrated that it was a symmetrical melanocytic tumor; it exhibited prominent pleomorphism and definitely showed changes of maturation (Fig. 1B~D). We detected hemorrhage crusts on the horny layer, but these were caused by the patient's scratching. There was no bleeding in his clinical course. Atypical epithelioid and spindle-shaped melanocytes with large hyperchromatic pleomorphic nuclei were observed. No ulceration was present. These findings were discordant with pigmented epithelioid melanocytoma1. His immunologic profile was consistent with a melanocytic tumor: S-100, Melan-A, and HMB-45 positivity, and CD34 negativity. The presence of diffuse HMB-45 positivity, even deeper in a nest, was considered unusual in a Spitz nevus. The extremely controversial nature of the lesion led to a diagnosis of atypical Spitz neoplasm of indeterminate biologic potential or Spitzoid-type minimal deviation melanoma. After receiving informed consent from the patient's parents, we performed careful observation, considering the possibility of malignant tumor. He had a huge palpable inguinal lymph node on physical examination 4 months postoperatively. Magnetic resonance imaging and positron emission tomography scans showed a large metastatic superficial inguinal lymph node (Fig. 2). Under a diagnosis of Spitzoid melanoma with subsequent lymph node metastasis, we performed wide local excision (2-cm margin including the periosteum) of the lower leg and resurfaced the defect with a local flap procedure. Left inguinal lymph nodes including the superficial and deep node groups were completely dissected. Three of the nine harvested lymph nodes including the large lymph node exhibited metastasis. Atypical melanocytes similar to those in the leg lesion were found within the lymph node parenchyma. The patient was treated with adjuvant dacarbazine, nimustine, and vincristine chemotherapy 5 times over 6 months. At a recent follow-up 2 years later, he did not have any evidence of recurrence or metastasis. The 5-year survival rate of children between 11 and 17 years old with metastatic Spitzoid melanoma is 49%2. Recent studies suggest the prognosis of children with Spitzoid melanoma is better than that in adults even local metastases or positive sentinel lymph nodes are present3,4,5. However, some cases of incomplete excision of Spitzoid melanoma leading to systemic metastasis and death have been reported5. Therefore, in cases in which the diagnosis is uncertain despite further evaluations, it is necessary perform careful observation to prevent recurrence and metastasis as early as possible. Fig. 1 (A) A 10-mm dome-shaped pigmented nodule on the left lower leg. (B) Histopathology of the skin lesion; Breslow's thickness clearly exceeded 4 mm. No ulceration was present (H&E, ×10). (C) Abundant irregular nests of varying size and shape, ... Fig. 2 Magnetic resonance imaging (left panel) and anterior projection images from the positron emission tomography-computed tomography scan (right panel). Note the extensive left inguinal lymph node uptake (arrows). This sentinel lymph node was larger than ...

Protease-activated receptor 2 suppresses lymphangiogenesis and subsequent lymph node metastasis in a murine pancreatic cancer model.

Protease-activated receptor-2 (PAR-2) is a G protein-coupled receptor that functions as a cell-surface sensor for coagulation factors and other proteases associated with the tumour microenvironment. Pancreatic cancer cells express high levels of PAR-2 and activation of PAR-2 may induce their proliferation and migration. Interestingly, however, PAR-2 expression is increased in stroma-rich pancreatic cancer regions, suggesting a potential role of PAR-2 in the tumour microenvironment. Here, we assessed the importance of PAR-2 in the stromal compartment by utilizing an orthotopic pancreatic cancer model, in which tumour cells are PAR-2-positive, whereas stromal cells are PAR-2-negative. We assessed tumour weight and volume and analysed proliferation and (lymph)angiogenesis both in vivo and in vitro. We show that genetic ablation of PAR-2 from the stromal compartment inhibits primary tumour growth, which is accompanied by reduced vascularization in primary tumours and reduced in tube formation of vascular endothelial cells in vitro. In contrast to smaller primary tumours, the number of lymph node metastases was increased in PAR-2-deficient animals, which was accompanied by an increased number of lymphatic vessels. In vitro tube-formation assays show that PAR-2 does not inhibit the intrinsic tube-forming capacity of lymphatic endothelial cells, but that PAR-2 actually inhibits cancer cell-induced tube formation. Overall, stromal PAR-2 thus plays a dual role in pancreatic cancer development by potentiating primary tumour growth but limiting lymphangiogenesis and subsequent lymph node metastasis. Our data identify a novel role of PAR-2 in the tumour microenvironment and pinpoint PAR-2 as a negative regulator of lymphangiogenesis.

Fluorescence in situ hybridization analysis of atypical melanocytic proliferations and melanoma in young patients.

Morphologic heterogeneity among melanocytic proliferations is a common challenge in the diagnosis of melanoma. In particular, atypical melanocytic lesions in children, adolescents, and young adults may be difficult to classify because of significant morphologic overlap with melanoma. Recently a four-probe fluorescence in situ hybridization (FISH) protocol to detect chromosomal abnormalities in chromosomes 6 and 11 has shown promise for improving the classification of melanocytic lesions. We sought to determine the correlation between FISH results, morphology, and clinical outcomes in a series of challenging melanocytic proliferations in young patients. We retrospectively performed the standard four-probe FISH analysis on 21 melanocytic neoplasms from 21 patients younger than 25 years of age (range 5–25 years, mean 14.6 years) from Stanford University Medical Center who were prospectively followed for a median of 51 months (range 1–136 months). The study cohort included patients with 5 confirmed melanomas, 2 melanocytic tumors of uncertain malignant potential (MelTUMPs), 10 morphologically challenging atypical Spitz tumors (ASTs), and 4 typical Spitz nevi. FISH detected chromosomal aberrations in all five melanomas and in one MelTUMP, in which the patient developed subsequent lymph node and distant metastasis. All 10 ASTs, 4 Spitz nevi, and 1 of 2 MelTUMPs were negative for significant gains or losses in chromosomes 6 and 11q. Our findings demonstrated a strong correlation between positive FISH results and the histomorphologic impression of melanoma. This finding was also true for the MelTUMP with poor clinical outcome. Therefore FISH may serve as a helpful adjunct in the classification of controversial melanocytic tumors in young patients.

口腔扁平上皮癌におけるMUC1ムチン上のDF3エピトープの発現は腫瘍悪性度,後発リンパ節転移および予後不良と関連する

口腔扁平上皮癌におけるMUC1ムチン上のDF3エピトープの発現は腫瘍悪性度,後発リンパ節転移および予後不良と関連する

Stage I・II筋層浸潤舌扁平上皮癌における後発転移と予後：210例の検討

本研究は後発転移と予後の予知因子として筋層浸潤の深さと角化を評価するのを目的とした。1987～2009年に癌研病院頭頸科で舌部切単独治療を受けたStage I・II舌扁平上皮癌の210例を解析した。筋層浸潤の深さは5mm以上，5mm未満とした。筋層浸潤最深部に注目し角化を癌真珠が顕著な癌真珠形成型62例，癌真珠は顕著でないが高度～中等度の角化がある不全角化型98例，角化が弱い～なしの非角化型50例に評価した。筋層浸潤5mm以上では，転移率は癌真珠形成型が69%（20/29），不全角化型が73%（22/30），非角化型が89%（8/9）であった。よって，筋層浸潤5mm以上は後発転移の強力な予知因子であろう。この210例のうち患側頸部郭清を受け追加治療のない76例の予後を解析した。癌真珠形成型で筋層浸潤5mm未満は8例全例が予後良好であった。5mm以上の46%（7/15）が頸部再発死，7%（1/15）が遠隔転移死であった。不全角化型と非角化型は，筋層浸潤3mm未満で予後不良の83%（5/6）と100%（2/2）が頸部再発死，3mm以上で予後不良の64%（7/11）と57%（4/7）が遠隔転移死であった。よって，筋層浸潤と角化は後発転移の予後に関係していた。

Detection of subsequent cervical lymph node metastasis in a patient with gingival carcinoma using computed tomography perfusion with a single-compartment kinetic model

We present a preliminary case report on the application of computed tomography perfusion (CTP) with a single-compartment kinetic model for early detection of subsequent lymph node metastasis in gingival carcinoma. A 47-year-old female patient with squamous cell carcinoma of the right lower molar gingiva (cT1N0M0) was reviewed. At 4 months after the initial treatment, a subsequent lymph node metastasis was suspected on monthly follow-up ultrasonography. She provided written informed consent prior to participating in the study, which had been approved by the institutional review board at our institution. After a standard head and neck contrast-enhanced CT examination, CTP images were acquired with a coverage of 32 mm (64 × 0.5-mm thickness) and a total acquisition time of 45 s, initiated at 5 s after intravenous infusion of 40 ml of 370 mg I/ml non-ionic iodine contrast agent at a rate of 4 ml/s. Post-processing of the CTP data was performed with dedicated software based on a single-compartment kinetic model (Ziosoft Inc., Tokyo, Japan). The SC flow parameter represented the blood flow per unit volume of tissue, in milliliters per minute per milliliter (i.e., min−1). The mean SC flow value was 1.144 min−1 in a totally replaced metastatic node and 0.985 min−1 in a partially replaced node, compared with 0.787 min−1 in the contralateral benign node. In conclusion, CTP with a single-compartment kinetic model is considered to be one of the useful methods for detection of a small non-necrotic subsequently developing metastatic cervical lymph node.

Stage I・II舌扁平上皮癌におけるポドプラニン発現様式と頸部リンパ節後発転移との関係

筋層浸潤5mm未満の舌扁平上皮癌では潜在性の頸部リンパ節転移を臨床的あるいは病理学的なパラメーターで予測するのは困難である。最近の報告で，癌細胞におけるポドプラニンの発現と転移との強い関係が示唆されている。本研究では，ポドプラニンのモノクロナール抗体であるD2-40を用いて染色した筋層最深部の腫瘍胞巣におけるポドプラニン発現を評価し，筋層浸潤5mm未満のStage I，II舌扁平上皮癌における頸部リンパ節後発転移へのインパクトを検討した。リンパ節転移は，腫瘍胞巣にびまん性に広くポドプラニン発現がみられた症例の42%（10/24）にみられ，一方でポドプラニン発現が弱いか無い症例では4%（1/24）にみられたのみであった。これらの結果から，ポドプラニンが筋層浸潤5mm未満のStage I，IIの舌扁平上皮癌症例における潜在性リンパ節転移の予測因子として役立つことが示唆された。

68Ga-DOTATATE-PET/CT Positive Metastatic Lymph Node in a 69-Year-Old Woman With Merkel Cell Carcinoma

We report the case of a 69-year-old woman with a Merkel cell carcinoma (MCC) in whom subsequent lymph node metastasis was first diagnosed by 68Ga-Dotatate-PET/CT followed by histopathological confirmation. MCC is an extraordinarily rare and aggressive neuroendocrine tumor of dermal origin with a high rate of postoperative recurrence. Owing to its rarity, the diagnosis of MCC remains a significant challenge. In our case, 68Ga-Dotatate-PET/CT proved clinically useful for diagnosing the lymph node metastasis of a MCC.

Outcome of sentinel lymph node biopsy and prognostic implications of regression in thin malignant melanoma

Thin melanomas with partial or complete regression may provide clues about antitumor immunity, but their management remains controversial. We have characterized the management and clinical outcomes of regressed thin (<1 mm) T1a melanomas and hypothesized that regression increases the risk of regional metastases when compared with nonregressed thin melanomas. A prospectively collected clinical database was reviewed, and T1a melanomas with regression were identified. Histology, surgical approach, outcome, and survival were evaluated. The primary outcome measures were sentinel node positivity, subsequent lymph node metastasis, and survival. A total of 75 patients with T1a or in-situ melanomas were grouped into three subsets. Group 1: 35 underwent a sentinel node biopsy (SNBx), none of which were positive. No patients developed nodal recurrence. The 5-year survival of this group was 93%, with a median follow-up of 52 months. Group 2: 31 were followed up without SNBx; two developed regional nodal disease (6.5%), neither of whom died of subsequent distant disease. The 5-year survival was 89%, with a median follow-up of 38 months. There was no significant difference in the survival between groups 1 and 2. Group 3: nine patients presented with metastatic disease concurrent with a regressed thin melanoma. These patients had a median survival of 2.3 years and a 4-year survival estimate of 22%. Regression should not be used as an indication for SNBx in T1a melanomas; we recommend that such patients be managed with wide local excision and a long-term clinical follow-up. The poor prognosis of thin regressed primary melanoma with simultaneous metastatic disease may indicate the existence of immune escape phenotypes supporting melanoma progression.