Pagetoid Spread Research Articles

The utility of intraoperative retroareolar margin frozen section assessment and the management of atypical epithelial proliferative lesions at the retroareolar margin in nipple-sparing mastectomies

ObjectivesNipple-sparing mastectomy (NSM) has become more frequently utilized due to superior psychological and cosmetic outcomes. The aim of this study was to evaluate the accuracy and utility of intraoperative frozen section evaluation of the retroareolar margin (RAM) in NSM. The management of atypical epithelial proliferative lesions at the RAM was also reviewed and discussed. MethodsA single institution, retrospective analysis was performed on all therapeutic NSM patients with intraoperative evaluation of the RAM from 2014 to 2018. Patient demographics, tumor characteristics, pathologic assessment of the RAM, surgical management, and clinical follow-up were reviewed. ResultsSeventy-four nipple-sparing mastectomies with intraoperative evaluation of RAMs were identified. Concordance was 95% between frozen and permanent section diagnoses with 4 cases representing false negatives and no false positives. There were no instances of nipple-areolar complex (NAC) recurrence in all cases with preserved NACs (mean follow up: 750 days). In the 9 cases where NACs were excised based on intraoperative RAM evaluation, the findings in the excised NACs were negative in 6 and ductal carcinoma in situ in 3 cases. Postoperative measurement of the tumor to nipple distance was the only statistically significant variable associated with a positive RAM by multivariable logistic regression (OR 0.475; 95% CI 0.238–0.946). ConclusionsIntraoperative RAM evaluation demonstrated high concordance with permanent histology. Negative RAM, including atypical epithelial proliferative lesions, led to NAC preservation without recurrence. Positive RAM alone did not predict NAC involvement, although pagetoid spread of ductal carcinoma in situ along nipple ducts may predict NAC positivity.

腫瘤を形成しない肛門腺由来肛門管癌pagetoid spreadの1例

腫瘤を形成しない肛門腺由来肛門管癌pagetoid spreadの1例

Pagetoid tumour spread in periocular sebaceous gland carcinoma: a comparative analysis in 130 patients.

To compare the clinical features, histopathology features, treatment, and prognosis of patients with and without pagetoid tumour spread secondary to periocular sebaceous gland carcinoma (SGC). Retrospective study of 130 patients with SGC who underwent conjunctival map biopsy. Of the 130 patients with SGC, 30 (23%) patients had histopathology proven pagetoid tumour spread. On multivariate analysis, increasing tumour basal diameter (p < 0.001) was predictive of pagetoid tumour spread. The odds ratio for tumour basal diameter in prediction of map biopsy positivity for pagetoid tumour spread was 1.13 (95% CI, 1.07-1.19). The sensitivity and specificity of clinicopathological correlation of pagetoid tumour spread was 57 and 90%. Overall, globe salvage was better in those without pagetoid tumour spread compared to those with pagetoid tumour spread (95% vs 33%; p < 0.0001). Comparing those with pagetoid tumour spread vs those without, the 5-year Kaplan-Meier estimate of systemic metastasis was 21% vs 4% (p = 0.15) and death was 28% vs 4% (p = 0.21), respectively. Increasing tumour basal diameter can predict the risk of pagetoid tumour spread. Every mm increase in tumour basal diameter increases the risk of pagetoid tumour spread by 13%. Map biopsy is recommended for all patients with periocular SGC's. Though the globe salvage rates are poor in those with pagetoid tumour spread, the occurrence of systemic metastasis and death are not significantly higher compared to those without pagetoid tumour spread.

A Case of Anal Canal Cancer with Pagetoid Spread Treated by Tri-Specialty Hybrid Surgery to Preserve Anal Function

A Case of Anal Canal Cancer with Pagetoid Spread Treated by Tri-Specialty Hybrid Surgery to Preserve Anal Function

Sebaceous Gland Carcinoma: Influence of Age at Presentation on Outcomes.

To assess the relationship between age at presentation and outcomes of patients with periocular sebaceous gland carcinoma. Retrospective case series of 241 patients. Of 241 cases, 29 (12%) were young adults (≤40 years), 122 (51%) were middle-aged adults (41-60 years), and 90 (37%) were older adults (>60 years). Based on the eighth edition of American Joint Committee on Cancer, most tumors belonged to T1 category (n = 78, 32%) on presentation. Wide excisional biopsy was the most common treatment modality (n = 183, 79%). There were no statistically significant differences in the clinical presentation, treatment approaches, and histopathology features amongst different age groups, except pagetoid spread which was higher in middle-aged adults (61%, p = 0.004). The incidence of tumor recurrence was higher in older age group compared to younger age groups, with 5-year, 10-year Kaplan-Meier estimate at 31%, 31% in young adults, 38%, 38% in middle-aged adults, and 45%, 100% in older adults (p = 0.03), respectively. The 10-year Kaplan-Meier estimate rate of locoregional lymph node metastasis, systemic metastasis, and death was higher in young adults (51%, 48%, and 48%, respectively) compared to middle-aged (30%, 17%, and 12%, respectively) and older adults (24%, 25%, and 27%, respectively), but the differences were not statistically significant. There is no difference in the clinical presentation of periocular sebaceous gland carcinoma based on age. However, the tumor recurrence rate is much higher in the older age group and death higher in younger patients despite the same treatment strategies in all age groups.

Clinicopathological diversity and outcome of longitudinal melanonychia in children and adolescents: analysis of 35 cases identified by excision specimens.

Longitudinal melanonychia in paediatric patients often represents a difficult diagnostic challenge, and studies emphasising its clinical and histopathological features are limited due to its low incidence in childhood. We retrospectively analysed 35 paediatric cases identified by excision specimens on their clinicopathological features, and performed fluorescence in-situ hybridisation on 13 available cases. Fingernails (77.1%) were more likely to be affected. Total melanonychia and Hutchinson's sign were observed in 10 (28.6%) and 14 (40.0%) cases, respectively. Nail dystrophy at diagnosis was present in five cases. After complete excision of the lesions, four patients relapsed during follow-up (mean=38months). Seventeen cases were diagnosed as lentigines and 18 as naevi, among which 11 cases were categorised as lentigines/naevi with atypical melanocytic hyperplasia. Mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and peri-ungual skin involvement were found in 25.7% (9 of 35), 40.0% (14 of 35), 40.0% (14 of 35) and 40.0% (14 of 35) of cases, respectively. Thirteen cases tested by fluorescence in-situ hybridisation showed no copy number aberration at the probed loci. There was a statistically significant difference in the following features between patients aged less and more than 10years (P<0.05): cytomorphology, mild-to-moderate nuclear atypia, confluency of melanocytes, focal pagetoid spread and melanocyte count. Some concerning clinicopathological characteristics, which are signs indicative of melanoma in adults, are not uncommon in paediatric longitudinal melanonychia, especially in patients aged≤10years. Owing to the extremely low incidence of melanoma in paediatric longitudinal melanonychia, in most circumstances a more conservative clinical management strategy should be adopted.

Application of 3-dimensional reflectance confocal microscopy: Melanocytic proliferations as three-dimensional models

To the Editor: Melanoma on chronically sun-damaged skin (MSDS) is challenging to detect.1Sanchez M.I. Rabinovitz H.S. Oliverio M.C. Elgart G.W. Grichnik J.M. Confocal microscopy of challenging dermoscopic diagnoses.Arch Dermatol. 2012; 148: 1224Crossref PubMed Scopus (1) Google Scholar Reflectance confocal microscopy (RCM) increases diagnostic accuracy but relies upon interpretation of 2-dimensional (2D) horizontal sections. Our objective was to determine whether existing technology could be used to create 3-dimensional (3D) models, which would expand on data available for discriminating skin biology. Melanocytic cells have different morphologic appearances dependent on developmental stage, activation status, and pathogenic genetic and epigenetic alterations. Cell shape, therefore, can provide clues to a cell's behavior. We reconstructed individual melanoma cells from stacks of RCM images (Fig 1; Supplemental Fig 1, available via Mendeley at https://data.mendeley.com/datasets/7kx38d9h2v/3). Distinct morphologies could be identified, including spindle, spheroid, and heavily dendritic cell forms. These 3D reconstructions also allowed for modeling of the nuclear shapes (Fig 1, insets). Because image sizes are known, it is possible to calculate nuclear and cellular volumes, which may also increase diagnostic accuracy.2Chang C.K. Tsai C.C. Hsu W.Y. et al.Segmentation of nucleus and cytoplasm of a single cell in three-dimensional tomogram using optical coherence tomography [published correction appears in J Biomed Opt. 2017;22(3):39801].J Biomed Opt. 2017; 22: 36003Crossref PubMed Scopus (11) Google Scholar Monomorphism or pleomorphism of melanocytes may also provide clues to diagnosis. In some tumors, cells are relatively uniform, presenting as sheets of spindle-shaped cells, monomorphic spheroidal-shaped cells, or heavy mats of dendrites. However, other tumors display more variation with epithelioid, spindle-shaped, and dendritic morphologies all appearing in a 500-μm field (Supplemental Fig 2). Location is also important in diagnosis. The presence of melanocytic cells in the middle to upper epidermis (pagetoid spread) may suggest malignancy, whereas cells in the superficial dermis suggest invasion. Within the context of the 3D volume, we used renderings to show upper (epidermal) and lower (dermal) regions simultaneously (Supplemental Fig 3). This can be used not only for identification of pagetoid and invasive cellular locations but also for examining the extent of melanization of cells in different locations that may imply differences in maturation. When visualizing normal pigmented skin and some benign pigmented neoplasms with RCM, bright rims (edging) around the dermal papillae are visible as rings when viewed in the horizontal plane, primarily due to melanin-containing basal keratinocytes. By rendering the stack on the vertical axis, the normal arrangement of refractile cells along the papillae is apparent (Fig 2, Supplemental Fig 4). Epidermal thickness can be calculated, as well as the length of epidermal ridge and volume of dermal papillae in 3D. When MSDS is present, asymmetric pigmentation (partially edged or nonedged dermal papillae) may be noted around dermal papillae.3Serrano P.F.-C. Segurado-Miravalles G. González S. Reflectance confocal microscopy in oncological dermatology.in: Nouri K. Lasers in Dermatology and Medicine. Springer, 2018: 375-400Google Scholar This phenomenon may be due to nonuniform melanin transfer or melanoma cell population density differences. The dermoepidermal junction also frequently becomes flattened in malignant tumors. These phenomena may be best evaluated in 3D. The 3D modeling process currently has limitations. When manual segmentation techniques are used, the more complex models take hours to produce, limiting bedside use. The imaging area is limited to the stack dimensions (500 μm × 500 μm). RCM image stacks are anisotropic, thus the noncubic voxels require interpolation and resampling to render accurately in 3D space.4Trusk T.C. 3D reconstruction of confocal image data.in: Gray W. Price J.R.L. Basic Confocal Microscopy. Springer, Cham2018: 279-307Crossref Google Scholar In summary, 3D modeling of confocal images can provide supplementary information, beyond what is appreciable in 2D images, including melanocyte morphology, volume, pleomorphism, and location. 3D modeling also allows for detailed evaluation of the dermoepidermal contour, which may reflect the summation of keratinocytic, melanocytic, immunologic, and microenvironmental events.

Pagetoid Spread of Sebaceous Cell Carcinoma over the Cornea

Pagetoid Spread of Sebaceous Cell Carcinoma over the Cornea

Eyelid sebaceous gland carcinoma: An assessment of the T classification of the American Joint Committee of Cancer TNM staging system 8th versus 7th edition.

To assess the prognostic values of the T classification of the 8th edition of the American Joint Committee of Cancer staging system and compare it to the 7th edition. Multicenter retrospective study of patients with eyelid sebaceous gland carcinoma. The primary outcome measure was the differences between outcomes when tumors were staged with either 7th or 8th edition. The measures evaluated included presenting features, management, histopathology, metastasis, recurrence, and mortality. Of the 60 patients (median age 73 years), 31 (51.7%) were females. A change in T staging occurred in 39 patients (65%) when the 8th edition was applied. Advanced categories (T3/T4) were significantly associated with nodal metastasis (p = 0.037) using the 8th edition criteria but not with the 7th edition (p = 0.066). The 8th edition T categorization significantly correlated with eye survival (p = 0.022) while the 7th edition did not (p = 0.058). Applying the 8th edition, category T4 at presentation was associated with a higher risk of nodal metastasis (p = 0.037) but not associated with local recurrence, distant metastasis, or tumor-related death (p = 0.281, p = 0.737, p = 0.319, respectively). T3/T4 category tumors were significantly associated with poor tumor differentiation (p = 0.001), and papillary histologic pattern (p = 0.024) but not with pagetoid spread (p = 0.056). The application of the 8th edition AJCC staging system for eyelid SGC may accurately predict nodal metastasis. Local recurrence and distant metastasis were not significantly associated with T classification, using either edition. Poor tumor differentiation and papillary pattern were associated with T3/T4 categories suggesting that pathological features may assist in determining prognosis.

Histopathologic Analysis of Signet-ring Cell Carcinoma In Situ in Patients With Hereditary Diffuse Gastric Cancer.

Hereditary diffuse gastric cancer (HDGC) is a rare autosomal dominant syndrome associated with an increased risk of developing Laurén's diffuse-type gastric carcinoma and lobular breast carcinoma. Although signet-ring cell carcinoma (SRCC) in situ (SRCC-pTis) has been reported as a characteristic lesion in HDGC cases with CDH1 germline mutations (CDH1 pathogenic variant), and a precursor of conventional intramucosal SRCC (SRCC-pT1a), its histopathologic features and specificity have not been sufficiently clarified. Here, we examined gastrectomy samples from 6 Japanese HDGC patients with CDH1 germline mutation, belonging to 4 families, and analyzed SRCC lesions histologically and immunohistochemically. Of the 274 foci found in the 6 samples, SRCC-pT1a accounted for 225 lesions (range: 8 to 107, mean 45.7 lesions per patient), while 46 foci were of SRCC-pTis (range: 1 to 15, mean 7.67 foci per patient). All SRCC-pTis foci were observed in the fundic gland area and on the superficial side of the mucosa. Histologically, tumor cells of SRCC-pTis were found between normal foveolar epithelial cells and the basement membrane, following a typical pagetoid spread pattern. Immunohistochemically, E-cadherin expression was lost in SRCC-pTis (27/28, 96.4%) more frequently than in SRCC-pT1a (95/197, 48.2%; P<0.001). To elucidate the specificity of SRCC-pTis for HDGC, 60 samples (range: 0.12 to 1.49 m, total 28.8 m of mucosal length) from gastric cancer cases were analyzed as controls, in which no SRCC-pTis were identified. Our results indicate that SRCC-pTis is a distinct histologic feature with high specificity for HDGC cases with CDH1 germline mutations.

Anal canal adenocarcinoma with pagetoid spread and inguinal lymph node metastasis treated with preoperative chemoradiotherapy: A case report.

Perianal Paget's disease is a rare condition, which is not usually accompanied by cancer. Here, a case of anal canal carcinoma with pagetoid spread and inguinal lymph node metastasis, which exhibited a significant response to preoperative chemoradiotherapy (CRT), is presented. A 58-year-old woman was admitted to The University of Tokyo Hospital with a complaint of discomfort around the anus. Physical examination revealed an erythematous inflamed skin lesion in the perianal region and a tumor of 15 mm in diameter detected on palpation in the left inguinal region, which was diagnosed as metastatic adenocarcinoma by excisional biopsy. Colonoscopy revealed moderately differentiated adenocarcinoma of 15 mm in diameter in the anal canal. Skin biopsy of the perianal region revealed an infiltration of pagetoid cells, which were positive for cytokeratin 7, and negative for cytokeratin 20 and gross cystic disease fluid protein 15. Based on these results, the patient was diagnosed as having anal canal adenocarcinoma with pagetoid spread. The patient received preoperative CRT including the bilateral inguinal region. After CRT, robotic-assisted laparoscopic abdominoperineal resection was performed. The macroscopic findings of the surgical specimen confirmed the formation of a scar as a result of the preoperative CRT. Microscopic examination of the anal tumor revealed no residual carcinoma or lymph node metastasis. In conclusion, this case may suggest the potential applicability of preoperative CRT for the local control of anal canal carcinoma with pagetoid spread.

Diagnostic accuracy of pigmented labial macules by in vivo reflectance confocal microscopy and correlation among techniques

Pigmented labial macules (PLMs) are clinical, dermoscopic, and histopathologic challenges. To describe and evaluate the utility of reflectance confocal microscopy (RCM) in PLMs and to establish a correlation between dermoscopy, RCM, histopathology, and immunohistochemistry. Prospective study of PLMs from 4 tertiary referral dermatology centers. The study included 51 biopsy specimen-proven PLMs. Dermoscopic, RCM images, and histopathologic preparations were evaluated for malignant criteria. Diagnostic accuracy of RCM for melanoma diagnosis, RCM Lip Score previously reported, and κ values between techniques were calculated. Included were 5 melanomas and 46 benign PLMs. Dermoscopically, melanomas exhibited more frequently ≥3 colors and ≥3 structures. With RCM, pagetoid spreading, epithelial disarray, continuous proliferation of atypical cells around papillae, nonhomogeneously distributed papillae, marked cellular atypia, and a higher number of dendritic cells per papillae were more frequent in melanomas. The RCM Lip Score was significantly higher in malignant lesions. Good κ values were observed in most of the evaluated features. A perfect sensitivity and specificity was obtained combining dermoscopy and RCM. A low number of melanomas were obtained. RCM improves lip melanoma diagnosis, and the RCM Lip Score represents a useful tool for the evaluation of a PLM.

Superficial sarcomas with CIC rearrangement are aggressive neoplasms: A series of eight cases.

CIC rearranged sarcomas have significant overlap with Ewing sarcoma, are aggressive, and typically present in deep soft tissue. They most commonly have a t(4;19)(q35;q13) with CIC-DUX4 fusion. Superficial presentation is rare. We report eight (6F, 2M; median 45-years-old, range 14-65) superficial CIC-rearranged sarcomas, involving the extremities (n = 4), vulva (n = 2), and trunk (n = 2). The tumors were composed of nodules/sheets of round cells with necrosis and hemorrhage separated by dense hyaline bands. Tumor cells had vesicular chromatin, prominent nucleoli and frequent mitotic figures. One showed pagetoid spread. Targeted next-generation sequencing was positive for CIC-DUX4 fusion (6/6); fluorescence in situ hybridization (FISH) was positive for CIC rearrangement (2/3). Eight of eight had evidence of CIC-DUX4 fusion/rearrangement by molecular techniques. Immunohistochemistry was positive for CD99+ (8/8) and DUX4+ (4/4). FISH for EWSR1 rearrangement was negative (5/5). Of five patients with at least 6 months follow-up, three of five died of disease, all within 2 years of presentation. One is alive with disease at 48 months. One is disease free at 3 months. Superficial CIC-rearranged sarcomas should be considered in cases exhibiting features reminiscent of Ewing sarcoma, but with increased pleomorphism and/or geographic necrosis. In contrast to superficial Ewing sarcomas, superficial CIC-rearranged sarcomas are aggressive.

Treatment Outcome of Anal Canal Cancer with Pagetoid Spread in Japan

Treatment Outcome of Anal Canal Cancer with Pagetoid Spread in Japan

1807 Esophageal Melanocytosis: An Uncommon Finding

INTRODUCTION: Esophageal melanocytosis is a benign, rare melanocytic proliferation in the basal layer of the squamous epithelium. The etiology of the melanocytosis is not clear; however, it has been suggested that aberrant migration during embryogenesis and chronic irritation such as GERD could lead to its occurrence. While largely asymptomatic, these proliferations raise concern for mucosal melanoma. CASE DESCRIPTION/METHODS: A 69-year-old Trinidadian female with past medical history of gastroesophageal reflux disease (GERD) presented with a two week history of dysphagia. Physical examination did not reveal any cutaneous or mucocutaneous lesions. Neurological exam also was normal. A computerized tomography (CT) scan showed circumferential wall thickening and moderate patulous proximal esophagus. A barium esophagram revealed severe esophageal dysmotility and GERD. Given dysphagia and CT findings, an esophagogastroduodenoscopy (EGD) was performed revealing hyperpigmented mucosa in the lower third of the esophagus (Figure 1A). Biopsies revealed melanin within the basal squamous epithelium with evenly spaced melanocytes and pigmented dendritic processes (Figure 1B). Immunohistochemistry for Melan-A and SOX10, a nuclear marker of melanocytes, highlighted these melanocytes without nesting or pagetoid scatter (Figure 1C). The patient was scheduled for a follow-up EGD for monitoring in 12 months. DISCUSSION: Endocscopically, anal and colonic lesions have been discovered along with esophageal lesions. Esophageal lesions largely present in the middle and lower third of the esophagus. Initial visualization of these lesions should be managed with a biopsy to determine if melanoma is present. Should esophagael melanocytosis be discovered on biopsy, repeat EGD with biopsy is recommended as early melanoma-in-situ may closely mimic esophageal melanocytosis.

Melanin bleaching with potassium permanganate for melanocytic lesions diagnosis in veterinary medicine

ABSTRACT The aim of this study was to microscopically re-evaluate the melanocytic lesions diagnoses established by the Animal Pathology Laboratory of the Federal University of Uberlândia, in the state of Minas Gerais, Brazil, over a period of eleven years; in addition, to perform a comparative analysis between the conventional histopathological (CH) method and the use of the melanin bleaching (MB) technique with potassium permanganate, sulfuric acid, and oxalic acid solutions. The results of the MB method presented a disagreement in 24.32% of the diagnosis previously by CH, with low agreement (61.0%) and low Kappa coefficient (0.2267). Melanoma was the most frequent lesion, more frequent in elderly and non-breed female dogs. The most frequent melanoma location was in the cutaneous tissue. The presence or absence of a pagetoid spread in cutaneous samples, distribution of melanin, pattern of cell layout, cell morphology, degree of cellular atypia, and the number of mitoses verified after MB were the most important criteria to confirm the diagnosis of malignancy or benignity of the lesions. Evaluating pathologists considered MB to be essential for the majority of diagnoses and an efficient complementary method for the diagnosis of melanocytic lesions, even in cases with a moderate degree of pigmentation.

Predictors of Local Recurrence for Eyelid Sebaceous Carcinoma: Questionable Value of Routine Conjunctival Map Biopsies for Detection of Pagetoid Spread.

To identify clinicopathologic factors associated with local recurrence of eyelid sebaceous carcinoma and determine whether routine conjunctival map biopsies are necessary to detect pagetoid spread. The authors searched PubMed for articles on eyelid sebaceous carcinoma and pagetoid spread published in English during 1982 to 2018, and they reviewed 99 consecutive patients with eyelid sebaceous carcinoma who underwent surgical excision with frozen section control of margins performed by 1 author (BE) during 1999 to 2017. Local recurrence rates after surgery were 5% to 25% in the literature and 6% in the authors' cohort. Risk factors for local recurrence included T3b (>20 mm) or worse disease according to the AJCC Cancer Staging Manual, eighth edition, pagetoid spread, diffuse growth pattern, and multicentric origin. Pagetoid spread was observed in 8.3% to 70% of patients in the literature and 31% of patients in the authors' cohort. The literature review showed that surgical excision with frozen section control is the mainstay of management of eyelid sebaceous carcinoma, with topical chemotherapy and cryotherapy used in cases with pagetoid spread. The authors found no solid evidence for added value from routine 4-quadrant conjunctival map biopsies, and some studies called into question their accuracy and yield. In patients with eyelid sebaceous carcinoma, meticulous microscopic margin control is appropriate in all cases and particularly for tumors >20 mm and adjuvant topical chemotherapy should be considered for tumors with conjunctival pagetoid spread. Routine conjunctival map biopsies are not essential, but targeted map biopsies of areas with signs suggestive of pagetoid intraepithelial spread may be appropriate to guide future closer observation or adjuvant treatments.

Polypoid Compound Melanocytic Proliferations: A Clinicopathological Study

Nevi can show a polypoid appearance both clinically and histologically. Anecdotally, polypoid compound melanocytic nevus may exhibit a spectrum of junctional architectural and cytologic atypia, at times creating a diagnostic challenge by mimicking the radial growth phase of melanoma. To investigate this issue, we prospectively reviewed 40 polypoid compound melanocytic proliferations without overt malignant features. The lesions frequently occurred in young female patients and were predominantly from the trunk and intertriginous areas. Commonly observed atypical features included asymmetry (30%), shouldering (47.5%), poor circumscription (37.5%), and deep extension of melanocytes along the adnexal structures (67.5%). Severe cytologic junctional atypia (22.5%), dermal mitoses (10%), and pagetoid spread of melanocytes (5%) were less commonly seen. All lesions showed a reassuring dermal component with negligible cytologic atypia and maturation with depth. Overall, 7 lesions could not be readily classified as benign nevus; 5 of these in which a benign diagnosis was strongly favored were classified as atypical polypoid compound melanocytic nevi, whereas 2 lesions with diffuse severe junctional cytologic atypia and dermal mitoses were classified as ambiguous melanocytic proliferations. Atypical/ambiguous lesions were significantly larger and predominantly located in the axilla and groin. On molecular studies, none of the lesions tested showed the molecular profile of melanoma. We confirmed that polypoid compound melanocytic nevus can exhibit a variable degree of junctional atypia, likely related to frequent episodes of trauma and regeneration resulting in melanocytic proliferation. Pathologists should be aware of this phenomenon to avoid overdiagnosis.

Recurrent Vulvar Melanoma – a Case Report

Abstract Melanoma rarely develops in the genital area. It is responsible for 5% of all vulvar malignancies. Postmenopausal women are usually more affected and the main differential diagnosis is vulvar melanosis and vulvar nevi. There are limited numbers of studies on dermoscopic features of mucosal melanoma, particularly early-stage lesions. Dermoscopic criteria have been described for the diagnosis of vulvar melanosis, and observational studies have been conducted to define the dermoscopic features of nevi and melanoma on the vulva. We are presenting the case of a 69-year old female with suspected recurrence of vulvar melanoma who previously had surgical removal of mucosal lentiginous melanoma on the left labia minor in June 2017. Five months after the primary melanoma surgery, the patient noticed de novo pigmentation at the left and right labia minor and urethral opening. On clinical examination, irregular light-brown pigmentation with ill-defined borders was evident on the labia minora of the vulva and around the external urethral orifice. On dermoscopy, irregular pigmented network, with white scar-like and structureless pinkish areas was evident. Incisional biopsy of the vulvar mucosa revealed melanoma in situ, confirming the local recurrence. CT scans of the head, thorax, abdomen and pelvis and gynaecological examination revealed no secondary deposits. Ultrasound of the regional inguinal lymph nodes revealed enlarged suspected pathologic involvement of the lymph nodes in both inguinal regions. Lymph node fine needle aspiration of lymph nodes in the left and right inguinal area revealed pleomorphic infiltrate of lymphoid cells with hemosiderin or melanoma pigment in the cytoplasm. Cystoscopic findings were within normal range. Interdisciplinary tumour board indicated wide excision of melanoma with margins of 1 cm and resection of the urethra, as well as biopsy of the enlarged left inguinal lymph node. Histopathological analysis of the resected mucosa revealed lentiginous spread of melanocytes showing moderate atypia, with focal pagetoid spread, without mitoses and ulceration and without invasion of lamina propria. The resection margins were tumour-free. Non-specific lymphadenitis was diagnosed on lymph node histopathological analysis. The patient was regularly monitored by a dermatologist and urologist, and had no recurrence. The accurate and prompt diagnosis is essential in the case of the vulvar melanoma which has unfavourable and unpredictable prognosis, with a tendency of local recurrences and regional and distant metastases in the case of invasive melanoma. In order not to miss early mucosal melanoma, dermatologists and gynaecologists should not avoid biopsy of lesions that demonstrate any clinical or dermoscopic feature of atypical melanocytic lesion, especially in case of the development of irregular pigmentation that expands and changes over time, the appearance of a solitary amelanotic papule or nodule requires excision or, in case of large diameter lesions, incision biopsies. Larger studies are needed to define more rigorously clinical and dermoscopic criteria that accurately distinguish early mucosal melanomas from benign skin lesions.

Intraductal Oncocytic Papillary Neoplasms: Clinical-Pathologic Characterization of 24 Cases, With An Emphasis on Associated Invasive Carcinomas.

Intraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a rare tumor. Recent molecular data indicate that it is distinct from other intraductal neoplasms; however, its clinicopathologic characteristics, especially the frequency/significance of an invasive carcinoma component, and biologic behavior remain to be fully defined. Clinicopathologic characteristics and survival of 24 IOPNs were analyzed. By definition, all tumors exhibited intraductal growth and oncocytic morphology. The female:male ratio was 1.7, and mean age was 59. In 44% of the patients, the IOPN was discovered incidentally; however, the working diagnosis was "ductal adenocarcinoma" in 42%. Fourteen IOPNs occurred in the head of the pancreas. The median tumor size was 4.5 cm. The tumors often grew along adjacent benign ducts, mimicking invasion, but only 29% exhibited unequivocal invasive carcinoma, mostly in the form of microscopic foci (pT1a=4, pT1b=1, pT2=2), and only 6% had lymph node metastasis. Invasive carcinoma was predominantly composed of small tubular units lined by oncocytic cells, or individual oncocytic cells infiltrating the periductal stroma. Follow-up information was available for 18 patients (median=6.8 y). No patients died from the disease, and the overall 10-year survival was 94%. Patients with invasive carcinoma trended toward a lower 5-year recurrence-free survival than those with noninvasive IOPNs (66% vs. 93%, P=0.066), but overall survival was not impacted by the presence of invasion (P=0.38). IOPN is a distinct tumor type in the pancreas. Despite its morphologic complexity and often extensive pagetoid spread to adjacent ducts, conventional invasive carcinoma is seen in only 29% and usually as microscopic foci. Thus, it is not surprising that IOPN exhibits indolent behavior even when invasion is present.