High-grade Histologic Features Research Articles

Giant Cell Tumor of Soft Tissue: An Updated Review.

Giant cell tumor of soft tissue (GCTST) is a locally aggressive mesenchymal neoplasm of intermediate malignancy that predominantly occurs in the superficial soft tissue of the extremities. It is histologically similar to a giant cell tumor of bone (GCTB) and shows a mixture of round to oval mononuclear cells and osteoclast-like multinucleated giant cells. Currently, immunohistochemistry plays a very limited role in the diagnosis of GCTST. Primary or secondary malignant GCTST has recently been described and tumors exhibiting high-grade histological features demonstrate higher rates of distant metastasis. GCTST lacks the H3-3A gene mutations that are identified in the vast majority of GCTBs, suggesting a different pathogenesis. Surgery is the standard treatment for localized GCTST. Incomplete surgical resection is usually followed by local recurrence. Radiation therapy may be considered when the close proximity of critical structures prevents microscopically negative surgical margins. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

Adamantinoma-like ewing sarcoma arising in the pancreatic tail: a case report of a rare entity and review of the literature

ALES is a rare subtype that demonstrates the EWSR1-FLI1 translocation characteristic of ES and demonstrates complex epithelial differentiation including diffuse cytokeratin and p40 expression. It has predominantly recognized in the head and neck and is common in middle-aged population. This case is the first case of ALES reported in the pancreatic tail, sharing some morphological characteristics with ALES in the head and neck, including monotonous cytology, infiltrative growth pattern, and complex epithelioid differentiation, but ALES in the head and neck often has high-grade histological features (e.g., necrosis, high mitotic rate, etc.), and sudden keratinization can also occur, but these features were not reflected in this primary pancreatic tail ALES. Although ALES arising in the pancreatic tail and in the head and neck sites share the immunohistochemical and molecular profile, our case can provide new ideas in differential diagnosis of ALES arising in pancreatic tail and promote increased recognition and understanding of ALES.

When Surgery Won’t Cut It: Successful Management of Eruptive Squamous Atypia With Combination Medical Therapy

The term eruptive squamous atypia (ESA) is used to describe squamous proliferations that do not present with high-grade histologic features and for which surgical management may exacerbate the condition. Non-surgical management of ESA with radiation, local or systemic chemotherapy, retinoids, or immunotherapy have been reported with variable success. In contrast, combination treatment with retinoids, immunomodulatory or chemotherapeutic agents may result in a more durable response. We report a case of recalcitrant ESA of the lower extremities where complete clinical remission was induced with triple combination medical management with intralesional 5-fluorouracil, field treatment with topical 5-fluorouracil and imiquimod, and oral acitretin. Our case adds to the literature supporting combination medical therapy for challenging cases of ESA.

Prognostic Factors in Pseudomyxoma Peritonei with Emphasis on the Predictive Role of Peritoneal Cancer Index and Tumor Markers

Pseudomyxoma peritonei (PMP) is a rare peritoneal condition where mucus-secreting tumorous cells progressively produce a thick, gelatin-like substance. The prognosis of patients with PMP is determined by the degree of cellularity within the mucin (low-grade (LAMN) vs. high-grade (HAMN) histologic features) and by the extent of the disease. Prognostic relevance of tumor markers CA19-9 and CEA, gender, Peritoneal Cancer Index (PCI), and completeness of cytoreduction (CC) after cytoreductive surgery were evaluated on 193 consecutive PMP patients, based on a retrospective analysis of prospectively gathered data from a German tertial referral center. We demonstrated that low PCI, CC0 status, low-grade histology, and female gender were independent positive prognostic factors for both overall survival (OS) and progression-free survival (PFS). Furthermore, LAMN patients with achieved CC0 status show significantly better OS and PFS compared to those with CC1 status (p = 0.0353 and p = 0.0026 respectively). In contrast, the duration and drug of hyperthermic intraperitoneal chemotherapy (HIPEC) were not prognostic in any comparison. Increased CA19-9 and CEA levels were significantly associated with HAMN cases, but also predicted recurrence in patients with low-grade histologies. Our study confirmed the prognostic role of tumor markers and emphasized the importance of CC status and PCI in a large cohort of PMP- and LAMN patients.

Glioblastoma lacking necrosis or vascular proliferations: Different clinical presentation but similar outcome, regardless of histology or isolated TERT promoter mutation.

Abstract The survival outcome of glioblastomas lacking necrosis of vascular proliferations is controversial, especially in glioblastomas with only an isolated TERT promoter mutation. Limited evidence suggests a favorable outcome for these patients, which challenges the concept of the proposed CNS5 classification of glioblastoma. In this study we assessed the impact on survival of the lack of necrosis or vascular proliferations in glioblastoma, and investigated the impact of isolated TERT promoter mutations. Although the clinical presentation is different, we did not find a favorable outcome for glioblastoma patients lacking high grade histological features or for patients with an isolated TERT promoter mutation.

S3411 Extensive Hepatic Lesions From a Primary Duodenal Neuroendocrine Carcinoma in a Young Male

Introduction: Neuroendocrine neoplasms (NEMs) are relatively rare, accounting for 0.5% of newly diagnosed malignancies. NEMs can be found throughout the body with two-thirds arising in the GI tract and incidence increasing among duodenal NEMs. These malignancies have a female predominance and generally occur in the 6th decade of life. This is a case of advanced metastatic disease from an unexpected duodenal neuroendocrine carcinoma in a healthy young male. Case Description/Methods: A 29-year-old male, with no PMH, acutely developed sharp RUQ abdominal pain. Prior to this, he was in his usual state of health. In the ED, the patient was hemodynamically stable with tenderness to palpation in the RUQ. Initial labs showed WBC 12.10 × 103/uL, Hgb 11.7 g/L, AST 55 U/L, ALT 173 U/L, ALP 127 U/L, and TBIL 0.8 mg/dL. CT A/P showed multiple well-circumscribed liver lesions, largest measuring 8.6 × 7.8 cm, with portal venous invasion (Figure A). CA 19-9 and CEA were negative. There was elevation of AFP 1,577 ng/mL and LDH 817 U/L, but negative hCG. A1AT, ANA, AMA, ASMA, ALKM, and ceruloplasmin were negative. Liver biopsy showed a poorly-differentiated malignant neoplasm of unknown primary. EGD was performed revealing a fungating mass in the second portion of the duodenum (Figure B). Pathology favored a high-grade poorly-differentiated neuroendocrine carcinoma (Figure C). He was discharged with palliative cisplatin/irinotecan initiation. Discussion: Gastrointestinal NEMs have been increasing in prevalence due to improved awareness. When carcinoid symptoms are absent, detection is dependent on imaging and endoscopy after the patient presents with complications from metastasis or mass effect. Following biopsy, GI NEMs are classified by WHO 2010 criteria into 3 groups based on mitotic count and Ki-67 index. Group 3 tumors are classified as poorly-differentiated neuroendocrine carcinomas with Ki-67 >20% with higher rates of angioinvasion and metastatic potential. Lymph node metastasis occurs in 60% of duodenal NETs, while liver mets occur in < 10%. In our case, the patient’s Ki-67% index was >90%, characterizing it as a Group 3 NEM. Characterization is important given the impact on prognosis and treatment. Group 3 NEMs have the overall worst prognosis. Since >90% of duodenal NEMs do not cause a clinical syndrome and are not associated with metastatic disease, surgical or endoscopic resection is preferred. However, if there is metastatic disease or high-grade histologic features, chemotherapy is the mainstay of treatment.Figure 1.: A, CT A/P with multiple large heterogeneously enhancing liver lesions concerning for metastatic malignancy of unknown primary (B) Large fungating mass located in the second portion of the duodenum (C) Duodenal mass, H&E stain, 20×, high-grade poorly differentiated epithelial malignancy composed of nested cells with indistinct nucleoli, moderate eosinophilic cytoplasm, and brisk mitosis.

Molecular Pathological Characteristics of Thyroid Follicular-Patterned Tumors Showing Nodule-in-Nodule Appearance with Poorly Differentiated Component.

Simple SummaryPoorly differentiated thyroid carcinoma (PDTC) is aggressive and is reportedly evoked by well-differentiated thyroid follicular-patterned tumors (TFTs). TFTs showing nodule-in-nodule (NN) appearance with PD component (PDc) but neither invasion nor metastasis are uncommon and are regarded as benign nodules despite their high-grade histological features. Our study aimed to preliminarily assess the potential role of PDc in NN in PDTC carcinogenesis using dual-color immunofluorescence of 53BP1 as a DNA damage response (DDR) molecule and the Ki-67, NRAS codon 61, and TERT-promoter (TERT-p) mutations. The prevalence of abnormal type 53BP1 expression and NRAS and TERT-p mutations in PDc was comparable to that of carcinomas. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations. Therefore, PDc in NN is potentially a precursor lesion associated with PDTC.Thyroid follicular-patterned tumors (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules. Although PDc exhibits histologically aggressive features relative to the outer nodule (Out-N), its pathological significance remains unclear. TP53 binding protein-1 (53BP1) is a DNA damage response (DDR) molecule that rapidly localizes at DNA double-strand breaks. Using dual-color immunofluorescence with Ki-67, the profile of 53BP1 expression is shown to be significantly altered during diverse tumorigenesis. In this study, we aimed to elucidate the malignant potential of PDc at the molecular level. We analyzed the profile of 53BP1 expression and NRAS codon 61 and TERT-promoter (TERT-p) mutations in 16 cases of TFTs showing NN with PDc compared to 30 adenomatous goiters, 31 follicular adenomas, 15 minimally invasive follicular carcinomas (FCs), and 11 widely invasive FC cases. Our results revealed that the expression level of abnormal type 53BP1 and incidence of NRAS and TERT-p mutations in PDc were comparable to FCs, suggesting a malignant potential. Because co-expression of 53BP1 and Ki-67 can be an indicator of altered DDR, the development of PDc in NN may be associated with DDR impairments after harboring NRAS and TERT-p mutations.

Prospective genomically guided identification of "early/evolving" and "undersampled" IDH-wildtype glioblastoma leads to improved clinical outcomes.

BackgroundGenomic profiling studies of diffuse gliomas have led to new improved classification schemes that better predict patient outcomes compared to conventional histomorphology alone. One example is the recognition that patients with IDH-wildtype diffuse astrocytic gliomas demonstrating lower-grade histologic features but genomic and/or epigenomic profile characteristic of glioblastoma typically have poor outcomes similar to patients with histologically diagnosed glioblastoma. Here we sought to determine the clinical impact of prospective genomic profiling for these IDH-wildtype diffuse astrocytic gliomas lacking high-grade histologic features but with molecular profile of glioblastoma.MethodsClinical management and outcomes were analyzed for 38 consecutive adult patients with IDH-wildtype diffuse astrocytic gliomas lacking necrosis or microvascular proliferation on histologic examination that were genomically profiled on a prospective clinical basis revealing criteria for an integrated diagnosis of “diffuse astrocytic glioma, IDH-wildtype, with molecular features of glioblastoma, WHO grade IV” per cIMPACT-NOW criteria.ResultsWe identified that this diagnosis consists of two divergent clinical scenarios based on integration of radiologic, histologic, and genomic features that we term “early/evolving” and “undersampled” glioblastoma, IDH-wildtype. We found that prospective genomically guided identification of early/evolving and undersampled IDH-wildtype glioblastoma resulted in more aggressive patient management and improved clinical outcomes compared to a biologically matched historical control patient cohort receiving standard-of-care therapy based on histomorphologic diagnosis alone.ConclusionsThese results support routine use of genomic and/or epigenomic profiling to accurately classify glial neoplasms, as these assays not only improve diagnostic classification but critically lead to more appropriate patient management that can improve clinical outcomes.

Prediction of Recurrence Risk in Solid Pseudopapillary Neoplasm of the Pancreas: Single-Institution Experience.

Background: Solid pseudopapillary neoplasm (SPN) of the pancreas is a low-grade malignant neoplasm with unpredictable behavior. Factors associated with recurrence were not conclusively identified. The aim of this study is to define the clinicopathological criteria for recurrence risk prediction in SPNs based on the most recent scientific evidence and to present our experience with SPNs.Methods: A retrospective review of patients with SPNs operated on in our institution from June 2012 to June 2018 was completed. Patient characteristics and clinical outcomes were analyzed. A detailed literature review was performed to evaluate the factors associated with the recurrence of SPNs.Results: The cohort consisted of 13 female patients with a median age of 24 years and a mean tumor size of 7.7 cm. Body and tail (53.8%) were the most common location, and distal pancreatectomy with splenectomy was the prevalent surgical procedure. One patient of SPN operated on for local recurrence after 11 years which had high-grade malignant histological features on the previously resected tumor. At a median follow-up of 42 months (range 36 to 108), all patients were disease free and alive. The proposed criteria for predicting recurrence in SPNs include tumor size >8 cm, synchronous metastasis, malignant SPN (according to 2000 or 2010 World Health Organization [WHO] criteria), lymphovascular invasion, pancreatic parenchymal invasion, and high Ki-67 index (>4%). All these are worse prognostic factors and should be considered as high-risk factors for postoperative relapse.Conclusion: The above-mentioned criteria can better predict SPN recurrence. Patients with high-risk features should undergo an extended follow-up.

A "Null" Pattern of p16 Immunostaining in Endometrial Serous Carcinoma: An Under-recognized and Important Aberrant Staining Pattern.

The ability to distinguish endometrial serous carcinoma (SC) from high-grade endometrioid adenocarcinoma is of great importance given their differences in prognosis and management. In practice, this distinction typically relies upon the use of a focused immunohistochemical panel including p53, p16, and mismatch repair proteins. The expression of p16 is characteristically strong and diffuse in SCs, and weak and/or patchy in many high-grade endometrioid adenocarcinomas. Here, we report a subset of SCs that are entirely negative for p16 immunostaining, a pattern we refer to as "p16 null." This pattern was identified in 2 of 63 cases of SC diagnosed at our institution-1 with histologically classic features and 1 with ambiguous high-grade histologic features. These tumors otherwise showed a SC signature by immunohistochemical and demonstrated an SC pattern of genetic mutations. No mutation in the gene for p16, cyclin-dependent kinase inhibitor 2A (CDKN2A), was identified in either case. However, molecular correlates for the absent p16 expression were present, including homozygous deletion of CDKN2A in one case and hemizygous deletion of CDKN2A with promotor hypermethylation of the remaining allele in the other case. To our knowledge, this constitutes the first report conclusively demonstrating the existence of a small subset of SCs that are completely negative by p16 immunohistochemistry, and the molecular lesions responsible for this pattern. In the context of an otherwise clinically and histologically classic example of SC, we endorse this "null" p16 staining pattern as an alternative aberrant staining pattern that should not deter one from committing to this diagnosis.

39. HPV-related multiphenotypic sinonasal carcinoma, an emerging entity in an unusual location: A case report

Background: Human papillomavirus (HPV)–related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a distinct tumour recently described in the sinonasal tract. This peculiar tumour exhibits morphologic features of a salivary gland tumour including admixed ductal and myoepithelial elements, as well as displays an unusual pattern of surface involvement with atypical squamous cells. It is associated with high-risk HPV. Most cases usually present as a large and destructive sinonasal mass with high-grade histologic features. Aim: We present a case report of HMSC arising in the floor of mouth of a 57-year-old Chinese man. Methods (clinical history): The patient was an ex-smoker who presented with a floor of mouth ulcer. The lesion was biopsy and was called a submucosal adenoid cystic carcinoma. Subsequently, the patient underwent wide resection of floor of mouth tumour, marginal mandibulectomy and neck dissection. Results (pathological findings): Macroscopic examination revealed an ulcerative tumour measuring 2.5 cm, extending to the margins. Microscopically, the tumour was composed of basaloid cells showing variable growth patterns including a cribriforming pattern that closely resembles adenoid cystic carcinoma. It was continuous with the mucosa that showed dysplastic squamous epithelium. On immunohistochemistry, the myoepithelial cells were positive for the myoepithelial markers. p16 was positive in both squamous and epithelial components. Metastatic carcinoma was present in two of the harvested lymph nodes. The patient developed pulmonary and liver metastases after two years of follow-up, which were confirmed histologically. Conclusions: This is the first case of HMSC reported in the floor of mouth, which behaves more aggressively as opposed to those arise from the sinonasal tract. It is important to recognise HMSC as they have a different clinical behaviour. The clue to the diagnosis is recognising the atypical squamous cells on the surface, corroborated by p16 positivity in tumour cells.

Histopathological and Clinical Differences Between Primary Breast Carcinomas With Neuroendocrine Features and Primary Breast Carcinomas Mimicking Neuroendocrine Features

We aimed to determine the histopathological differences between primary breast carcinomas with neuroendocrine features (NEBC) and carcinomas mimicking neuroendocrine features (NEBC-like). Twenty-three cases with NEBC, all showing positive staining for synaptophysin and/or chromogranin-A in ≥50% of tumor cells and 36 cases with NEBC-like (no staining for neuroendocrine [NE] markers but suspicious for NE morphology in terms of solid/trabecular growth patterns) were included in the study. Significant differences were found between the groups in terms of the patients' ages, histologic/nuclear grade of tumor, lymphovascular invasion, comedo-type ductal carcinoma in situ (DCIS), microcalcification, Ki-67 proliferation index, nuclear shape, and level of peritumoral lymphocytic infiltration. The presence of large-size solid cohesive groups of tumor cells; plasmocytoid, spindle, and/or columnar shapes of tumor cells; and eosinophilic-granular appearance of cytoplasm were mostly noted in the NEBC group. The presence of small- to medium-sized solid cohesive groups of tumor cells; high-grade histologic and nuclear features; clear cytoplasm; and round to ovoid nucleus were mostly noted in the NEBC-like group. No significant differences were found in terms of tumor size, ER/PR/HER2 status, as well as the presence of DCIS, elastosis, extracellular/intracellular mucin, signet ring cells, apocrine features, and accompanying papilloma or ductal ectasia. In conclusion, small- to medium-sized solid cohesive groups of tumor cells, high-grade features, clear cytoplasm, round to ovoid shape of nucleus, lymphovascular invasion, comedo-type DCIS, microcalcification, high level of Ki-67 proliferation index (≥20%), and moderate/strong level of peritumoral lymphocytic infiltration might support non-NE features in breast carcinomas.

Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity.

Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs.

Mucinous Tubular and Spindle-Cell Carcinoma of the Kidney: Clinical Features, Genomic Profiles, and Treatment Outcomes.

Mucinous tubular and spindle-cell carcinoma (MTSCC) is a rare kidney cancer subtype with limited cases reported in the literature. We report on outcomes of 25 patients with this variant who were managed at our institution. The institution database was queried, and clinical data extracted for patients with MTSCC. Molecular features examined included next-generation sequencing with Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets and allele-specific copy number analysis using the Fraction and Allele-Specific Copy Number Estimates from Tumor Sequencing (FACETS) algorithm in a subset of patients. All patients underwent primary tumor-directed therapy (nephrectomy= 23, cryoablation= 2). Metastases were diagnosed in 6 patients (24%), 3 (12%) of whom had de novo metastatic disease. Five of 6 patients with metastatic disease had high-grade histological features compared with 0 of 19 nonmetastatic patients (83% vs. 0%; P< .001, Fisher exact test). Three-year overall survival from diagnosis was 84.8% (95% confidence interval, 59.6-94.9) with a median follow-up time of 3.9 years (range, 1 month to 10.3 years). Three deaths occurred, all from metastatic disease. Four patients received systemic therapy with time to treatment failure≤6 months across different agents with the exception of 1 patient with prolonged response with sunitinib treatment (30.6 months). The most frequent molecular alterations were neurofibromin 2 mutations (n= 2; 40%), germline alterations (n= 2; 40%) including checkpoint kinase 2 and BRCA2 DNA repair associated mutations, multiple chromosomal copy number losses, and mismatch repair deficiency in 1 patient. MTSCC is characterized by localized tumors treated successfully with primary tumor-directed therapy. However, patients with high-grade histological features were more likely to develop metastatic disease with limited responses to standard therapies.

Female Sex Hormone Receptor Profiling in Uterine Adenosarcomas.

This study aimed to identify the hormonal receptor status in uterine adenosarcoma (AS) and uterine AS with sarcomatous overgrowth (AS + SO), including those with high-grade histologic features (nuclear pleomorphism, atypical mitoses, necrosis), with or without heterologous elements. Estrogen receptor (ER) status, including estrogen receptor α (ERα), estrogen receptor β (ERβ), and G protein-coupled estrogen receptor (GPER), and progesterone receptor (PgR) status were examined. From August 2001 to November 2013, 11 patients with histologic diagnosis of uterine AS were identified. Tumor tissue sections were stained for ERα, ERβ, GPER, and PgR and examined both for percentage of overall cells stained and for intensity of staining. Descriptive statistics were calculated using clinicopathologic data abstracted from the medical record. Eight cases of AS and 3 cases of AS with high-grade features were identified. Seven of 8 tumor samples of AS showed strong or moderate intensity immunostaining for ERα; all AS + SO tumor samples showed minimal to no immunoreactivity for ERα. There was a significant decrease in ERα H scores in high-grade tumors when compared with AS (P = 0.01). Lower PgR H scores were observed in high-grade tumors compared with those in AS (P = 0.04). Estrogen receptor β immunostaining was variable, and GPER immunostaining was absent in the majority of tumor samples. Higher expression of ERα and PgR was observed in AS when compared with those with AS + SO and high-grade features. Both tumor subtypes showed similar levels of ERβ and GPER expression, although significant differences in ERβ and GPER expression were not detected. In contrast to our previous findings in uterine carcinosarcoma, ERs ERβ and GPER do not seem to play a significant role in AS in this study.

HPV-related Multiphenotypic Sinonasal Carcinoma: An Expanded Series of 49 Cases of the Tumor Formerly Known as HPV-related Carcinoma With Adenoid Cystic Carcinoma-like Features.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC), originally known as HPV-related carcinoma with adenoid cystic carcinoma-like features, is a peculiar neoplasm that is restricted to the sinonasal tract, exhibits features of both a surface-derived and salivary gland carcinoma (particularly adenoid cystic carcinoma), and is associated with high-risk HPV. Given the limited number of published cases, the full clinicopathologic spectrum of this neoplasm is unclear. Here, we present an updated experience of 49 cases. All cases of HMSC were obtained from the authors' files. Immunohistochemistry for p16, c-kit, and myoepithelial cell markers (S100, actin, calponin, p63, and/or p40) was performed along with RNA in situ hybridization for HPV (type 33-specific as well as a high-risk cocktail). Fluorescence in situ hybridization studies for fusions of MYB, NFIB, and MYBL1 was performed on a subset of cases. Clinical follow-up was obtained from medical records. A total of 49 cases of HMSC were collected. Twenty-eight (57%) were from women and 18 (43%) from men, ranging in age from 28 to 90 years (mean, 54 y). Of 40 cases with detailed staging information, 43% of HMSCs presented with a high T-stage (T3 or T4). Histologically, most grew predominantly as solid nests of basaloid cells exhibiting high mitotic rates and frequent necrosis, with histologic and immunohistochemical evidence of myoepithelial differentiation. Most cases also demonstrated foci of cribriform and/or tubular growth, along with an inconspicuous population of ducts. Thirty-four (69%) cases demonstrated an unusual pattern of surface involvement where markedly atypical squamous cells colonized tracts of the sinonasal mucosa. Less consistent histologic features included squamous differentiation within the invasive tumor (n=6), sarcomatoid transformation (n=5) including overt chondroid differentiation (n=3), and prominent epithelial-myoepithelial carcinoma-like growth (n=3). All cases were positive for p16 by immunostaining and HPV by RNA in situ hybridization. Thirty-three (67%) were positive for HPV 33. No cases tested for MYB, MYBL1, or NFIB gene fusions were positive. In the 38 cases with follow-up data, (mean follow-up, 42 mo) 14 recurred locally and 2 metastasized (lung, finger). There were no regional lymph node metastases, and no tumor-related deaths. HMSC is a distinct sinonasal neoplasm characterized by myoepithelial differentiation, frequent surface epithelial involvement, and the presence of high-risk HPV (especially type 33). Although it classically exhibits a cribriforming pattern that closely resembles adenoid cystic carcinoma, our expanded series highlights a histologic spectrum that is much broader than previously recognized, warranting a change in terminology. HMSC usually presents as a large and destructive sinonasal mass with high-grade histologic features, but it paradoxically behaves in a relatively indolent manner, underscoring the importance of distinguishing HMSC from true adenoid cystic carcinoma, squamous cell carcinoma, and other histologic mimickers.

Correlation of Bronchial Lavage or Washing Cytology with High Grade Histologic Features in Primary Adenocarcinomas of Lung

Correlation of Bronchial Lavage or Washing Cytology with High Grade Histologic Features in Primary Adenocarcinomas of Lung

Sentinel Node Lymphoscintigraphy in High-risk Cutaneous Squamous Cell Carcinoma

BackgroundHigh-risk cutaneous squamous cell carcinoma includes recurrent disease, a tumor diameter > 2 cm, T4 stage, perineural or lymphovascular invasion, tumor depth of ≥ 4 mm, and high-grade histologic features. All have been implicated in an increased risk of occult regional lymph node involvement. Patients and MethodsAmong a large group of patients with nonmucosal, cutaneous squamous cell carcinoma seen at our center, 30 patients with high-risk inclusion criteria were prospectively evaluated to undergo wide local excision and sentinel lymph node mapping. ResultsWith a median follow-up period of 56 months, 4 patients (13%) had regional lymph nodal involvement. The patients identified with lymph node-positive disease underwent adjuvant therapy. Five patients (17%), none of whom had nodal disease at diagnosis, developed locally recurrent disease requiring additional therapy. On multivariate analysis, a statistically significant correlation was found between the depth of tumor invasion and occult sentinel lymph node involvement. ConclusionIn the present prospective analysis, sentinel lymph node mapping resulted in upstaging in 13% of the patients. The tumor depth was independently associated with an increased risk of nodal involvement. Given the association between a depth of tumor invasion of ≥ 4 mm and occult nodal disease in cutaneous squamous cell carcinoma, sentinel lymph node mapping could be considered an integral part of surgical staging for patients with high-risk features.

Chondrosarcomas of the hands and feet: A case series and systematic review of the literature

ObjectiveTo review the imaging features of chondrosarcomas (CS) of the hands and feet, with pathologic correlation. Materials and methodsFor 24 histologically-confirmed CS of the hands (n=14) and feet (n=10), 23 studies were retrospectively reviewed by two musculoskeletal radiologists in consensus. Radiographs (n=23), bone scintigrams (n=2), and magnetic resonance (MR) (n=7) images were evaluated for lesion location, cortical and medullary involvement, presence of perilesional signal abnormalities and soft tissue masses (STM). Pathologic specimens were reviewed for tumor grade (grade 1–3). Descriptive statistics were reported. ResultsCS occurred in adults (age range 32–92) and most were located in the digits (22/23 (95.6%)) rather than tarsal/carpal bones (1/23 (4.4%)). For digital CS, 21/22 (95.45%) involved the epiphysis in addition to the metadiaphysis, 22/23 (95.6%) exhibited >2/3 endosteal scalloping, and 16/23 (69.5%) were expansile (>50% of the bone width). Pathologic fractures (7/23 (30.4%)) and STMs (16/23 (69.6%)) were frequent. By MR, perilesional abnormalities were common (bone marrow edema in 6/7 (85%), soft tissue edema in 5/7 (71.4%), STM in 7/7 (100%)). Following contrast administration (n=6), there was solid (3/6 (50%)) or lobular (3/6 (50%)) enhancement. Bone scintigrams showed increased uptake on all phases (>anterior superior iliac spine (ASIS)). Pathology specimens revealed 17 grade 2 and 7 grade 3CS, with increased cellularity, necrosis and myxoid features. ConclusionCS of the hands and feet have common distinctive features, including involvement of the end-of-bone, significant endosteal scalloping, expansile appearance, a frequent STM, and intermediate to high grade histologic features. Additional aggressive imaging features are identified by MR (perilesional signal abnormalities) and bone scintigraphy (increased uptake>ASIS) that may be helpful clues to the diagnosis.

Prognostic classification of thyroid follicular cell tumors using Ki-67 labeling index: risk stratification of thyroid follicular cell carcinomas.

This review emphasizes that the so-called high-risk thyroid carcinoma is not a distinct tumor entity, but a group of tumors with different histologies. High-grade histological features, such as tumor necrosis, increased mitoses, and nuclear pleomorphism, together with high Ki-67 labeling index (more than 10%), are good indicators of high-risk thyroid carcinoma and suggest a possible risk for anaplastic transformation. This review proposes the stratification of patients with thyroid carcinoma into low-, moderate-, and high-risk groups based on Ki-67 labeling index, which should be useful for the clinical management of patients, even after initial surgery. Currently, both the aggressive variant of papillary carcinoma and poorly differentiated carcinoma are aggressively treated by a completion of total thyroidectomy with prophylactic lymph node dissection followed by radioactive iodine treatment. Therefore, patients with moderate-risk or high-risk thyroid carcinoma based on Ki-67 labeling index should also be considered candidates for this treatment strategy.