Superficial Spreading Type Research Articles

Report of Incidental Vulvar Malignant Melanoma Upon Dermatologic Evaluation for Vaginal Cyst

BACKGROUND: Vulvar malignant melanoma is a rare, often aggressive and recurring disease with a poorly understood prognosis. Here, we describe a patient with a longstanding vaginal cyst who was diagnosed with vulvar malignant melanoma upon a dermatologic evaluation. THE CASE: Our patient, a 53-year-old female, with a family history of a father with malignant melanoma presented for evaluation of a vaginal cyst present for over 20 years on her right labia that had become painful and began draining over the past year. She was seen twice at urgent care and was treated with oral antibiotics (unspecified) and referred to dermatology. A comprehensive dermatologic evaluation of the epidermal inclusion cyst in the right labia majora incidentally revealed a neoplasm of uncertain behavior in the right labia minora suspected for vulvar malignant melanoma (Figure 1). Shave biopsy of her right labia minora revealed a Stage 1B malignant melanoma, superficial spreading type, with a 1.1 mm depth of invasion (Breslow thickness) and 11 per 1mm2 mitotic count. Right partial radical vulvectomy and bilateral inguinal sentinel lymph node biopsies were performed. Pathology showed malignant melanoma with negative margins and negative nodes. Treatment and excision for her vaginal cyst was not initiated as her symptoms were not bothersome at the time of visit. She presented with a post-operative infection after 2 weeks which was suggestive of bilateral inguinal vulval acute cellulitis with no definitive abscess upon computed tomography (CT) scan. She was initially treated with vancomycin with additional piperacillin/tazobactam for a total of three days. Trimethoprim/sulfamethoxazole was later initiated for 14 days. Medical oncology referral for evaluation of metastasis revealed normal positron emission tomography-computed tomography scan. Notably, the patient had extensive confluent/atypical lentiginous basal melanocytic hyperplasia at the periphery which could not be distinguished from melanoma in situ. Upon tumor board consultation, scouting biopsies of her left labia majora were performed. Pathology showed melanocytic hyperplasia instead of residual malignant melanoma at the periphery. The patient now follows up every few months with dermatology and medical oncology. CONCLUSION: Given the often fast, aggressive spread of vulvar malignant melanoma, timely dermatologic evaluations are necessary. Among those at higher risk due to a personal or family history of malignant melanoma, regular total body skin cancer screenings are indicated. Further, the sensitive and typically sun-protected location of a vulvar malignant melanoma might preclude a dermatologic evaluation in this area and highlights the need for more comprehensive vaginal screenings and better communication between dermatologic and gynecologic medical care teams.

A case of superficial spreading type of poorly differentiated adenocarcinoma of the stomach with invasion to the esophagus

BackgroundInvasion is more likely to occur in gastric cancer affecting larger areas. Poorly differentiated adenocarcinoma tends to invade deep. The cardiac region prefers submucosal invasion because the submucosa is coarser than the other regions.Case presentationA 75-year-old man presented with a chief complaint of abdominal discomfort and weight loss. Esophagogastroduodenoscopy revealed an irregular ulcerative lesion with partial redness of the upper body and lesser curve of the stomach. A continuous shallow depressed lesion invaded the abdominal esophagus by approximately 40 mm. Poorly differentiated adenocarcinomas (por, sig) were observed on biopsy. Grossly, the cancer appeared to extend into the muscle layer; however, we could not confirm invasion into the muscle layer in our biopsy tissue. We diagnosed the lesion as a superficial spreading type of advanced gastric cancer and performed a total gastrectomy, D2-lymph node dissection (spleen preservation), Roux-en-Y reconstruction, and cholecystectomy. Postoperative histopathological examination revealed extensive infiltration of poorly differentiated adenocarcinoma (90 mm × 55 mm), and all were intramucosal lesions. The final pathological diagnosis was T1a, N0, M0, and Stage IA. The postoperative course was uneventful and the patient was discharged on postoperative day (POD) 11. Five years have passed since the operation, and the patient is alive without recurrence.ConclusionWe encountered a case of gastric carcinoma in which poorly differentiated adenocarcinomas expanded extensively. All lesions were intramucosal.

The clinicopathologic spectrum and genomic landscape of de-/trans-differentiated melanoma

Dedifferentiation and transdifferentiation are rare and only poorly understood phenomena in cutaneous melanoma. To study this disease more comprehensively we have retrieved 11 primary cutaneous melanomas from our pathology archives showing biphasic features characterized by a conventional melanoma and additional areas of de-/trans-differentiation as defined by a lack of immunohistochemical expression of all conventional melanocytic markers (S-100 protein, SOX10, Melan-A, and HMB-45). The clinical, histologic, and immunohistochemical findings were recorded and follow-up was obtained. The patients were mostly elderly (median: 81 years; range: 42–86 years) without significant gender predilection, and the sun-exposed skin of the head and neck area was most commonly affected. The tumors were deeply invasive with a mean depth of 7 mm (range: 4–80 mm). The dedifferentiated component showed atypical fibroxanthoma-like features in the majority of cases (7), while additional rhabdomyosarcomatous and epithelial transdifferentiation was noted histologically and/or immunohistochemically in two tumors each. The background conventional melanoma component was of desmoplastic (4), superficial spreading (3), nodular (2), lentigo maligna (1), or spindle cell (1) types. For the seven patients with available follow-up data (median follow-up period of 25 months; range: 8–36 months), two died from their disease, and three developed metastases. Next-generation sequencing of the cohort revealed somatic mutations of established melanoma drivers including mainly NF1 mutations (5) in the conventional component, which was also detected in the corresponding de-/trans-differentiated component. In summary, the diagnosis of primary cutaneous de-/trans-differentiated melanoma is challenging and depends on the morphologic identification of conventional melanoma. Molecular analysis is diagnostically helpful as the mutated gene profile is shared between the conventional and de-/trans-differentiated components. Importantly, de-/trans-differentiation does not appear to confer a more aggressive behavior.

Molecular Genetics in a Cohort of Patients With Concurrent PTC and Melanoma

PTC and melanoma are known to harbour common mutations, but this has not been extensively investigated. Targeted therapies for BRAF and PD-L1 have been used for melanoma and there are ongoing clinical trials for use of PD-L1 inhibitors in PTC but its utility is uncertain. Additionally, many of these patients have multiple cancers, so, whether they have a tumour predisposition syndrome is also unclear. Both germline and somatic mutations in BRCA1-associated protein 1 (BAP1) are associated with a wide spectrum of tumours. We hypothesized that a common genetic link may be present in our cohort of patients who have both PTC and melanoma.The aim of this study was to elucidate molecular genetics, specifically BRAF, NRAS, KRAS, KIT using OncoFocus Mass Array System as well as expression of PD-L1 and BAP1, using a standard antibody (SP263) and C-4 respectively, in an Australian cohort with concurrent PTC and melanoma.In our cohort of 21 patients (43% females, all Caucasian), melanoma was diagnosed about 8 years prior to PTC (50.3 ± 18.3 vs. 58.6 ± 12.8 years). The most common mutation was BRAFV600E seen in 88% of PTC, followed by NRAS mutation in 12% of PTC. Majority of the PTC (68%) stained negative for PD-L1. There was no significant association between PD-L1 tumour status and clinicopathologic outcomes. Interestingly, majority of multifocal, bilateral and both bilateral and multifocal PTC were PD-L1 negative (85%,69% and 69% respectively, P<0.05); only extrathyroidal extension was found to be associated with positive (≥1%) PD-L1 staining (83.3 vs.30.8; p=0.057). Regarding melanoma, clinicopathologic and mutation data were obtained for 15/21 patients and 8/15 patients respectively. Superficial spreading type of melanoma was present in 50% patients. The BRAFV600E and NRAS mutation were present in 3/8 patients each, and 2/8 patients had no mutations. PD-L1 staining was negative in 7/12 (58%) of melanoma tissues. Of the 5 cases that stained positive for PD-L1, 4 were at >25%, a much higher degree of staining compared to PTC group. Among 7 patients where data were available for both tissues, concordant mutations were found in only 2 patients (both BRAFV600E). In addition, 11 of the 21 patients had at least one other cancer apart from PTC and melanoma. Nine of the 11 patients who had more than one cancer were BRAF positive. BAP1 staining was retained in the majority of PTCs and melanoma tissues, indicating no loss of BAP1 protein.PTC and melanoma both share molecular markers including BRAF, NRAS, PD-L1 as shown in our cohort. This is the largest study describing the mutation status of both PTC and melanoma. It is also the only study describing the PD-L1 and BAP1 expression in PTC and melanoma. BRAFV600E was the most common mutation. Majority of the PTC and melanoma stained negative for PD-L1. BAP1 expression was retained in both either PTC and melanoma tissues thus making presence of BAP1 tumour predisposition syndrome unlikely.

Clinicopathological analysis of basal cell carcinoma – A retrospective study

Objectives: The objective of the study was to analyze the demographic profile, histopathological features, risk factors, and recurrence rates in patients with basal cell carcinoma. Materials and Methods: A retrospective study was conducted from 2012 to October 2018 in 29 patients with histopathologically confirmed basal cell carcinoma. All the patients had undergone either excision or cryotherapy as per the institution protocol. Information on the history of the disease, occupation, history of sun exposure and clinical and histopathological features were collected and analyzed. Results: A female preponderance was found (n = 18, 62.1%), majority of the patients were unemployed (44.8%), 19 patients (65.5%) gave a history of sun exposure, and the nose was the most common site of disease. Ten females (34.5%) did not have any excessive exposure to the sun, but gave a history of exposure to heat and fumes in the kitchen. Six patients (20.7%) had a preexisting nevus at the same site and superficial spreading type was the most common histopathological type (n = 24, 82.8%). Excision gave the best result. Four patients (13.8%) had recurrence of the disease. Limitations: Small sample size was the major limitation. The risk factors and occupation could not be analyzed objectively. Conclusion: This is a pioneer study from Kerala. A female preponderance (62.1%) was observed. The role of heat, fumes, type of oven, and use of reheated oil in cooking as risk factors for the development of BCC needs analysis in future studies. Superficial spreading type was the most common pattern observed in histopathology slides (82.8%). Excision gives near-complete clearance and a good cosmetic result with less risk of recurrence.

Superficial spreading type of early gastric cancer coexisting with multiple hyperplastic polyps

We encountered a rare case that involved the superficial spreading type of early gastric cancer coexisting with multiple hyperplastic polyps. An 81-year-old Japanese woman with a history of Helicobacter pylori infection was diagnosed with gastric cancer (cT1bN0M0), which presented as a wide, nodular, aggregated protrusion that was associated with multiple pedunculated and sessile polyps. Distal gastrectomy was performed, and the resected specimen involved an 8cm × 4cm nodular aggregated protruding lesion and 15 polyps that were 2-20mm in size. Histopathological examination revealed that the nodular aggregated protruding lesion was a mucosal adenocarcinoma and that the multiple polyps were hyperplastic. The coexistence of multiple hyperplastic polyps and mucosal adenocarcinoma with nodular aggregated protrusions suggested that the mucosal adenocarcinoma had developed from a fusion of multifocal hyperplastic lesions. This may have occurred via a hyperplasia-carcinoma sequence related to the Helicobacter pylori infection. The superficial spreading type of early gastric cancer has a potential developed from a fusion of multifocal hyperplastic polyps.

Establishing an endoscopic diagnostic process system (M-system) for gastric MALT lymphoma of superficial-spreading type.

Gastric mucosa-associated lymphoid tissue lymphoma is a rare disease, which is associated with a low endoscopic diagnostic accuracy even on tissue biopsy. We aimed to establish a diagnostic process system (M-system) using detailed magnifying endoscopy images to improve the diagnostic efficiency of this disease. First, 34 cases from 16 patients with the diagnosis of mucosa-associated lymphoid tissue lymphoma were collected as the study group. The control group included randomly selected patients who were diagnosed with early differentiated carcinoma, undifferentiated carcinoma or inflammation. Then, the endoscopic images of these patients were analyzed by senior physicians. Finally, the M-system was established based on the data extracted from the images reviewed, and its diagnostic efficiency for mucosa-associated lymphoid tissue lymphoma was validated by the junior physicians. A series of elements with high sensitivity and specificity for the diagnosis of mucosa-associated lymphoid tissue lymphoma on endoscopic images were extracted for the establishment of the M-system. Using the M-system, the diagnostic accuracy, sensitivity, specificity and correct indices of mucosa-associated lymphoid tissue lymphoma rose from 65.4 to 79.4%, 41.2 to 76.5%, 73.5 to 80.4% and 0.147 to 0.569%, respectively, all of which were statistically significant. The M-system can improve the diagnostic accuracy of mucosa-associated lymphoid tissue lymphoma of the superficial-spreading type on detailed magnifying endoscopy. This would help in the early diagnosis of the disease and treatment, which would translate into improved clinical outcomes.

Malignant Melanoma of the Female Genital Tract: Experience of an Oncology Center in Pakistan.

IntroductionMalignant melanoma, which arises from melanocytes or pigment cells, is one of the most common forms of epithelial cancer. Cutaneous and noncutaneous melanomas differ clinically and genetically. Mucosal melanomas are rare. In the female genital tract, the most frequent location of melanoma is the vulva, whereas the vagina is seldom affected. The occult nature of their anatomical location contributes to the late presentation and late diagnosis of vaginal melanoma, resulting in an exceedingly poor patient prognosis. The present study describes the incidence, symptoms, management, and prognosis of women in Pakistan with malignant melanoma of the vulva, vagina, and cervix.Materials and methodsThe Hospital Information System of Shaukat Khanam Memorial Cancer Hospital and Research Center was searched electronically to identify patients diagnosed with malignant melanoma from January 1995 to December 2017. Patients with cutaneous malignant melanoma, multiple primary tumors, and metastases to the female genital tract from primary tumors located elsewhere were excluded. All included patients had been diagnosed with primary malignant melanoma of the female genital tract.ResultsThe search of medical records identified 271 patients with malignant melanoma, of whom 13 had primary malignant melanomas of the female genital tract. Of these 13 patients, nine, three, and one had primary vaginal, vulvar, and cervical melanomas, respectively. Median age at presentation was 60 years (range, 30-70 years), with 10 patients being post-menopausal. The most common presentations were per-vaginal bleeding and per-vaginal discharge (five patients each). The mean duration of symptoms was 7.46 months. Seven patients underwent wide local excision. Six patients had nodular type malignant melanoma, two had superficial spreading type, and five were unclassified. Nine patients had pathological T4 disease, and two had pathological T3. Mean Breslow depth was 5.4 millimeters (mm), with 10 patients having tumor depth >4 mm. Eight patients were positive for the microscopic involvement of margins. The mean time to recurrence was 11.8 months (range, 1-24 months), and the mean time to metastasis was 17.6 months (range, 2-44 months). The median survival after surgery was 25 months (range, 2-75 months).ConclusionThis study is the first to report the incidence, symptoms, management, and prognosis of patients in Pakistan with malignant melanoma of the female genital tract. Meta-analyses and prospective multicenter studies are needed.

Abstract P3-08-38: Primary cutaneous melanoma of the breast in women. A retrospective study of 82 patients

Abstract Background: Primary cutaneous melanoma of the breast (PCMB) is a relatively uncommon type of melanoma staged according to the AJCC system for other cutaneous melanomas. However, whether their outcome is different from primary cutaneous melanomas of other sun-exposed sites and the features that predict outcome specifically in PCMB are currently unclear. Moreover, histologically, the breast skin is considered to be a special site for melanocytic lesions. Therefore, we analyzed a retrospective cohort of female PCMB patients to determine the clinical and primary tumor features that correlate with time-to-event outcomes of overall survival (OS) and disease specific survival (DSS). Design: We identified women with PCMB diagnosed and/or treated at our institution between 2002 and 2015. The following data were collected: clinical/ demographic features (age at diagnosis, ethnicity, anatomic site [nipple-areolar complex, upper, lower, medial, lateral]); primary tumor pathologic features (Breslow thickness, Clark level, ulceration, mitotic rate, vertical growth phase (VGP), regression, lymphovascular invasion (LVI), perineural invasion (PNI), tumor infiltrating lymphocytes (TIL) and cytology); and metastatic disease features (satellitosis, date and metastasis to sentinel and/or regional lymph nodes, clinical detectability of nodal metastasis, and date and site of distant metastases). Kaplan Meier methods, univariate and multivariate Cox proportional hazards regression models determined associations with OS and DSS. Results: 82 cases, including 16 in-situ and 66 invasive PCMBs were identified. Most patients were white (98%), with a median age at diagnosis of 40.5 years (range: 15-77). With a median follow up of 7.6 years, the 1, 3, 5, 10-year OS rates were 97.4%, 94.7%, 91.9% and 81.3%, respectively; the 1, 3, 5, 10-year DSS rates were 98.7%, 95.9%, 93.1% and 86.9%, respectively; the median OS and DSS were not reached. Thirteen patients developed metastasis: 5 regional only, 1 distant only and 7 both; of which 6 had metastatic disease at presentation. Eleven patients died, and 8 was due to progression of PCMB. Most of the invasive PCMB were of superficial spreading type (84.8%), with median tumor thickness of 0.47 mm. Univariate analysis of patients with invasive melanoma revealed the following features to be associated with shorter survival (Table 1): age at presentation, Breslow thickness, Clark level, ulceration, mitotic rate and VGP; while histologic type, anatomic site, LVI, PNI, regression, associated nevus, cytology, and TIL were not significant. Adjusting covariate of features significant in univariate analysis, the multivariate analysis demonstrated only Breslow thickness and ulceration to be independently associated with OS and DSS. Conclusion: Primary cutaneous melanomas of the breast often affects white adult women and increasing tumor thickness and ulceration are associated with shorter survival, similar to primary melanomas of other cutaneous sites. Table 1: Clinical and Primary Tumor Features Associated with Overall (OS) and Disease Specific Survival (DSS) in Primary Cutaneous Melanomas of the BreastUnivariate Analysis (p-value)Clinical/ primary tumor featureOSDSSAge at presentation ≥ 41.5 years0.0020.018Breslow Thickness0.0020.001Clark Level0.0040.003Vertical Growth Phase0.0430.038Mitotic Rate0.001&amp;lt;0.001Ulceration&amp;lt;0.001&amp;lt;0.001Regression0.2870.195Tumor Infiltrating Lymphocytes0.1370.278Lymphovascular Invasion0.1980.147Associated Nevus0.830.41Predominant Cytology0.7280.874Multivariate Analysis (p-value)Breslow Thickness0.0140.006Ulceration0.0060.017 Citation Format: Madhuchhanda Roy, Junsheng Ma, Aysegul A Sahin, Senthilkumar Damodaran, Michael T Tetzlaff, Jonathan L Curry, Ana M Ciurea, Jing Ning, Carlos A Torres-Cabala, Doina Ivan, Phyu P Aung, Merrick I Ross, Jeffrey E Gershenwald, Michael A Davies, Victor G Prieto and Priyadharsini Nagarajan. Primary cutaneous melanoma of the breast in women. A retrospective study of 82 patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-38.

A case of superficial spreading type of esophageal cancer resected endoscopically with combination of methods for prevention of stricture

A case of superficial spreading type of esophageal cancer resected endoscopically with combination of methods for prevention of stricture

Risk of Lymph Node Metastasis in Patients with the Superficial Spreading Type of Esophageal Squamous Cell Carcinoma

Background: Little is known about the clinicopathological characteristics of superficial spreading-type esophageal carcinoma extending ≥5 cm along the long axis of the esophagus. This study was aimed at investigating the frequency of lymph node metastasis (LNM) in patients with superficial spreading-type esophageal carcinoma. Methods: We reviewed the data of 320 patients with superficial esophageal squamous cell carcinoma who had undergone esophagectomy with lymph node dissection at our hospital between 1986 and 2010. The incidence of LNM was compared between the spreading (≥5 cm) and nonspreading (< 5 cm) types. Results: The multivariate analysis revealed significant differences in the likelihood of LNM depending on the lymphovascular invasion, the infiltrative growth pattern (INF)-c, and the depth. There was no difference in the LNM frequency between nonspreading and spreading type in the patients with epithelium (EP)-lamina propria, muscularis mucosa (MM)-submucosa (SM)1 and SM2/3 lesions. The frequencies of LNMs (nonspreading-type vs. spreading-type tumors) in the patients with MM-SM1 lesions were 7/47 (14.9%) versus 4/25 (16%) and those in the patients with SM2/3 lesions were 22/58 (37.9%) versus 4/14 (28.9%), when the lesions did not have lymphovascular invasion and INF-c. Conclusions: Endoscopic resection can be selected for ­EP-SM1 lesions, regardless of whether the lesions are of the spreading type or nonspreading type.

BRAF Mutation Status in Primary, Recurrent, and Metastatic Malignant Melanoma and Its Relation to Histopathological Parameters.

BackgroundBRAF mutations are a common finding in malignant melanoma (MM). Nevertheless, apart from their significance as a therapeutic target in advanced melanoma, their prognostic value is still debated.ObjectiveTo assess BRAF mutation status in primary, recurrent, or metastatic MM and its correlations with histopathological findings.MethodsWe analyzed 203 samples from 178 consecutive patients: 129 primary cutaneous MM, 49 metastatic and recurrent MM of unknown primary site, and 25 cases of recurrences or metastases of primary MM. BRAF mutations in exon 15 were identified with real-time polymerase chain reaction and/or direct sequencing or pyrosequencing. Histopathological examination was performed according to standard procedures.ResultsWe observed a 42.1% prevalence of BRAF mutations at codon 600 among our patients, 84% of whom harbored the V600E mutation. Mutations showed a statistically significant increase in younger patients (P = 0.011), in ulcerated tumors (P = 0.020), and in tumors lacking solar elastosis in adjacent dermis (P = 0.008). Mutations were also more common in male patients, as well as in primary MMs of the torso, and in nonvisceral metastases, however without reaching statistical significance. Logistic regression analysis identified type and ulceration as the only significant predictors of BRAF mutation. The highest frequencies of mutated BRAF were identified in superficial spreading and nodular types, and the lowest in acral lentiginous and lentigo maligna types. In situ MM and primary dermal melanoma displayed intermediate frequencies.ConclusionFrequency of mutated BRAF is type-related and correlated with ulceration, a known adverse prognostic factor.

Approach to Patients with Malignant Melanoma of Unknown Primary Origin.

Objectives:Although malignant melanoma accounts for 3% of skin cancers, it is responsible for 75% of deaths associated with skin cancer. In our study, all melanoma cases diagnosed and treated at our clinic were retrospectively reviewed, and the cases of unknown primary origin among them were examined in detail in terms of diagnosis and treatment.Methods:The patients with malignant melanoma treated at the inpatient services of our clinic between January 1991 and April 2017 were retrospectively screened in the records. These patients were evaluated for age, sex, tumor type, Breslow depth, metastasis, and treatment. Among these patients, four cases of unknown primary origin were examined in detail.Results:During January 1991 and April 2017, 173 patients received inpatient care for malignant melanoma at our clinic. As regards to the melanoma subtypes, nodular type in 45 patients, acral lentiginous type in 43 patients, superficial spreading type in 63 patients, lentigo maligna melanoma in 15 patients, subungual type in 7 patients, and either unidentified melanoma or other subtypes in 10 patients were identified.Conclusion:The ideal treatment of a patient with melanoma is multidisciplinary, with plastic surgery having a central role.

Combination of local and oral steroid use for stricture control after circumferential endoscopic submucosal dissection for superficial spreading type of esophageal cancer : A case report

The third edition of the guidelines for esophageal cancer clinical practice stated that there is no limitation in the circumferential range for endoscopic submucosal dissection (ESD) adaptation. However, the technical difficulty of broad esophageal ESD and the risk of stenosis after surgery are possible challenges encountered. We have experienced a case of superficial spreading type of esophageal cancer in which complete resection was achieved by circumferential esophageal ESD with the tunnel method. Local steroid injection and oral administration combination therapy was useful for controlling stenosis after ESD.

A Review of Photodynamic Therapy for Neoplasms of the Head and Neck.

Photodynamic therapy (PDT) involves the use of a phototoxic drug which is activated by low powered laser light to destroy neoplastic cells. Multiple photosensitizers have been studied and tumors have been treated in a variety of head and neck sites over the last 30years. PDT can effectively treat head and neck tumors, particularly those of the superficial spreading type, and the classic application of this technology has been in the patient with a wide field of dysplastic change and superficial carcinomatosis. Interstitial treatment has been used to treat more invasive cancer. Data is available from case series and institutional experiences, but very little randomized data is available. We review the mechanisms of action, historical development, available data, and current knowledge regarding PDT for the various head and neck subsites, and discuss possible future directions, with an emphasis on clinical application.

Morphological classification of intraductal papillary neoplasm of the bile duct.

To investigate the morphological classification of intraductal papillary neoplasm of the bile duct (IPNB), as well as morphological differences between IPNB without mucin secretion (IPNB-NM) and IPNB with mucin secretion (IPMN-B). Eighty-one patients with IPNB were retrospectively analysed. Imaging examinations included computed tomography (CT), magnetic resonance imaging (MRI), gadolinium-ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI and positron emission tomography-computed tomography (PET-CT). According to the morphology of tumours and extent of bile duct dilations, IPNB was classified into seven types: I, upstream-ductectatic type; II, typical type; III, superficial-spreading type; IV, no-mass-forming type; V, intrahepatic-cystic type; VI, extrahepatic-cystic type; and VII, infiltrating type. Thirteen IPNB-NM patients comprised type I (11 cases), type II (1 case) and type VII (1 case); 68 IPMN-B patients comprised type I (2 cases), type II (30 cases), type III (6 cases), type IV (11 cases), type V (13 cases), type VI (2 cases) and type VII (4 cases). Bile duct dilations were more severe in IPMN-B than in IPNB-NM. PET-CT and Gd-EOB-DTPA-enhanced MRI clearly demonstrated the extension of infiltrating IPNB. IPNB can be classified into seven morphological types. IPNB-NM and IPMN-B have different morphological features. • IPNB can be classified into seven morphological types. • IPNB-NM and IPMN-B have different morphological features. • Enhanced CT and MRI can display different types of IPNB. • Morphological classification of IPNB facilitates management of the disease.

Pharmacokinetic Study of Adjuvant Gemcitabine Therapy for Biliary Tract Cancer following Major Hepatectomy (KHBO1101).

BackgroundBiliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects.MethodsWe evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2′,2′-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800–1,000 mg/m2. Physical examination and adverse events were monitored for 12 weeks.ResultsThirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43–83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy.ConclusionMajor hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU.Trial RegistrationUMIN-CTR in (JPRN) UMIN000005109

Outcome of patients with de novo versus nevus-associated melanoma

Prior reports indicate a wide range of melanomas in histopathologic contiguity with a nevus, and an associated nevus has unclear prognostic implications in melanoma. We sought to investigate the relationship among nevus-associated melanomas, sentinel lymph node status, and overall survival. We conducted a retrospective analysis of 850 patients with cutaneous melanoma and sentinel lymph node removed at Massachusetts General Hospital from 1998 through 2008 and meta-analysis of the literature. Nevus-associated melanomas represented 28% (235/850) of cases and were significantly correlated with younger age (P= .03), truncal site (P= .0005), superficial spreading type (P < .0001), and absent ulceration (P= .005). There was no association with sentinel lymph node status (P= .94) and no survival difference between nevus-associated versus de novo melanoma (P= .41). Meta-analysis of over 4000 cases revealed a similar percentage of associated nevi (32%). This was a retrospective study. Approximately 30% of melanomas are associated with a nevus. The presence of a nevus associated with a melanoma has no prognostic implication in sentinel lymph node status or overall survival.

Indocyanine green and fluorescence lymphangiography for sentinel lymph node identification in cutaneous melanoma.

Sentinel lymph node (SLN) biopsy has become the standard method of determining regional lymph node involvement in cutaneous melanoma. Although traditionally performed via injection of radioisotope tracers and blue dyes, fluorescent lymphangiography with indocyanine green (ICG) is an attractive alternative. Fifty two consecutive patients with cutaneous melanoma of the trunk or extremities underwent SLNB. Preoperative lymphoscintigraphy was performed with technetium-99m sulfur colloid (TSC). Peritumoral intradermal injection of isosulfan blue (ISB) and ICG was then performed. Successful identification of a sentinel lymph node via each modality was then assessed. A total of 77 lymph nodes were identified from the 52 patients (range 1-3). The majority of melanomas were extremity-based, superficial spreading type, and had SLN localized to the axilla. There were no complications related to IcG administration. Rates of SLN detection were 96.2% for TSC, 59.6% for ISB, and 88.5% for IcG (P < 0.05 for ICG vs ISB). On univariate logistic regression analysis, no factors were found to be associated with failure of ICG. Fluorescent lymphangiography using ICG is an effective method of SLN identification in patients with cutaneous melanoma of the trunk and extremities. When ICG and TSC are used in combination, ISB offers no additional advantage and may be safely omitted.

Correlation of histologic regression in primary melanoma with sentinel node status.

The influence of regression on the status of the sentinel node (SN) is controversial. In many centers, the presence of regression in thin melanomas supports the performance of an SN biopsy. To identify whether regression in primary melanoma has any influence on SN involvement. Retrospective study of melanomas with a Breslow thickness greater than 0.75 mm and undergoing SN biopsy from January 1, 2003, through December 31, 2010, at Instituto Valenciano de Oncología, which receives melanoma patients from regional hospitals and dermatology practices. Only cases with paraffin blocks or histologic slides representative of the primary tumor and available for review were included in the study. Melanomas from 201 patients met these criteria and constitute the core of this study. Sentinel node biopsy in melanoma. Presence or absence of regression in the primary melanoma, type (early vs late), and extension were correlated with the presence or absence of metastasis in the SNs. In addition, the main clinical and histologic characteristics of the primary melanoma were correlated with the status of SN and the regression features. Regression was found in 52 melanomas (25.9%). Regression did not show a statistically significant association with SN status. When melanomas were subdivided by Breslow thickness into 4 groups, those with regression had a lower frequency of positive SNs in 3 of the 4 groups (≤1.00, 1.01-2.00, and >4.00 mm), although differences did not reach statistical significance in any group. We found no influence by type of regression or its extension on the SN status. Regression was found more frequently in thin melanomas (≤1.00 mm), melanomas located on an axial site, and superficial spreading or lentigo maligna melanoma types (P = .02, P < .001, and P = .03, respectively). Regression of the primary melanoma is not associated with a higher proportion of positive SNs. These data do not support the practice of performing SN biopsy in thin melanomas with regression in the absence of additional adverse prognostic characteristics.