Comparison of post-hepatectomy long-term survival outcome between non-colorectal non-neuroendocrine and colorectal liver metastases: A population-based propensity-score matching analysis.

BACKGROUND: Hepatectomy is an established treatment for colorectal liver metastasis (CLM) or neuroendocrine liver metastasis. However, its role in non-colorectal non-neuroendocrine liver metastasis (NCNNLM) is controversial. This study aims to compare long-term survival outcomes after hepatectomy between NCNNLM and CLM in a population-based cohort. METHODS: From 2009 to 2018, curative hepatectomy were performed in 964 patients with NCNNLM (n â€‹= â€‹133) or CLM (n â€‹= â€‹831). Propensity score (PS) matching was performed. Short-term and long-term outcomes were compared between PS-matched groups. Univariate and multivariate analyses were performed to identify prognostic factors affecting survival. RESULTS: There were 133 patients in the NCNNLM group and 266 patients in the CLM group. The mortality (1.5 â€‹% vs 1.5 â€‹%) and morbidity (19.5 â€‹% vs 20.3 â€‹%) rates were comparable between the two groups. There was no statistically significant difference in 5-year overall (48.9 â€‹% vs 39.8 â€‹%) and recurrence-free (25.1 â€‹% vs 23.4 â€‹%) survival rates between NCNNLM and CLM groups. A high pre-operative serum bilirubin level, severe postoperative complications and multiple tumors were independent prognostic factors for poor survival. CONCLUSION: Hepatectomy for selected patients with NCNNLM can achieve similar long-term oncological outcomes as those with CLM. High serum bilirubin, severe postoperative complication and multiple tumors are poor prognostic factors for survival.

Return to work after injury in Hong Kong: prospective multi-center cohort study.

PURPOSE: Trauma remains a major cause of morbidity and disability worldwide; however, reliable data on the health status of an urban Asian population after injury are scarce. The aim was to evaluate 1-year post-trauma return to work (RTW) status in Hong Kong. METHODS: This was a prospective, multi-center cohort study involving four regional trauma centers from 2017 to 2019 in Hong Kong. Participants included adult patients entered into the trauma registry who were working or seeking employment at the time of injury. The primary outcome was the RTW status up to 1 year. The Extended Glasgow Outcome Scale, 12-item Short Form (SF-12) survey and EQ5D were also obtained during 1-, 3-, 6-, 9-, and 12-month follow-ups. Multivariable Cox proportional hazards regression analysis was used for analysis. RESULTS: Six hundred and seven of the 1115 (54%) recruited patients had RTW during the first year after injury. Lower physical requirements (p = 0.003, HR 1.51) in pre-injury job nature, higher educational levels (p < 0.001, HR 1.95), non-work-related injuries (p < 0.001, HR 1.85), shorter hospital length of stay (p = 0.007, HR 0.98), no requirement for surgery (p = 0.006, HR 1.34), and patients who could be discharged home (p = 0.006, HR 1.43) were associated with RTW within 12 months post-injury. In addition, 1-month outcomes including extended Glasgow Outcome Scale ≥ 6 (p = 0.001, HR 7.34), higher mean SF-12 physical component summary (p = 0.002, HR 1.02) and mental component summary (p < 0.001, HR 1.03), and higher EQ5D health index (p = 0.018, HR 2.14) were strongly associated with RTW. CONCLUSIONS: We have identified factors associated with failure to RTW during the first year following in Hong Kong including socioeconomic factors, injury factors and treatment-related factors and 1-month outcomes. Future studies should focus on the interventions that can impact on RTW outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03219424.

Neoadjuvant palbociclib on ER+ breast cancer (N007): clinical response and EndoPredict's value.

The purpose of the study was to test the efficacy of neoadjuvant palbociclib therapy and to evaluate its impact on cell cycle arrest and changes in EndoPredict (EP) scores before and after treatment. Postmenopausal women with histologically proven ER+ve, HER2-ve invasive breast cancer, 2 cm or greater, were enrolled in an open-label, single-arm study. Twenty eligible patients were given letrozole 2.5 mg per day together with palbociclib 125 mg per day for 3 out of 4 weeks in repeated cycles for 16 weeks (4 cycles) before surgery. The primary end points were clinical response rates (cRR) and preoperative endocrine prognostic index (PEPI). The secondary end points were pathologic response and gene expression testing with EP test on collected tumor samples. The following results were obtained. 17 patients showed a clinical response of 50% or more, including 8 complete responses and 9 partial responses. There was significant reduction in area (P < 0.0001) and volume (P = 0.017) of the cancer. Pathologic complete response (pCR) was achieved in one patient; all cancers were downgraded after treatment. Ki67 (P = 0.044) and EP scores (P < 0.0001) were significantly reduced after treatment. Analysis of the relative gene expression levels showed that all proliferative genes, IL6ST and RBBP8 were decreased after palbociclib treatment. 6 patients with intermediate and three patients with high PEPI risk scores were found to have low EPclin scores. All patients with high PEPI relapse risk score had high EPclin score. In conclusion, effective clinical response was demonstrated by neoadjuvant letrozole in combination with palbociclib. Compared with PEPI, EPclin might be a better parameter to estimate prognosis after neoadjuvant therapy.

EGFR gene mutation study in cytology specimens.

Activating mutations of the epidermal growth factor receptor (EGFR) gene in non-small cell lung cancer predicts a significantly higher clinical response rate to tyrosine kinase inhibitors targeting EGFR, and it is currently recommended that patients under consideration for EGFR TKI as first-line therapy be tested for such mutations to determine the appropriateness of treatment. For lung cancer patients who present with advanced stage disease where surgical treatment is not indicated, cytology specimens obtained through bronchoscopy, drainage of body fluid, or fine-needle aspiration are the only means to obtain tumor cells for tissue diagnosis and EGFR gene mutation testing. We reviewed the experience of 1,410 consecutive EGFR mutation testing requests at a single institution in Hong Kong that comprised 269 cytology specimens and 1,141 surgical specimens. The material inadequacy issue in cytology specimens may be overcome by tumor cell enrichment strategies and employment of mutation detection techniques with increased analytical sensitivity. The use of cytology specimens to test for predictive molecular cancer biomarkers is without a doubt expected to increase, and cytopathologists should be closely engaged with the clinicians in the therapeutic process and become acquainted with new technology in order to directly participate in personalized oncology care.

Use of fludarabine-containing chemotherapeutic regimen results in durable complete remission of subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare lymphoma. The optimal therapy for SPTCL is undefined and the results of treatment with anthracycline-containing chemotherapy for aggressive cases have remained poor. A 27-year-old woman with multifocal and aggressive CD8+ SPTCL was treated with the purine analog fludarabine in combination with mitoxantrone and dexamethasone (FND). The patient achieved complete remission after one course of treatment. After completion of six courses of FND, the patient has remained in remission for more than 3 years. FND may be an effective treatment for aggressive SPTCL.

Follow-up study of atypical glandular cells in gynecologic cytology using conventional Pap smears and liquid-based preparations: impact of the Bethesda System 2001.

OBJECTIVE: This study evaluated the impact of the Bethesda System (TBS) 2001 in reporting of atypical glandular cells (AGC) when using conventional Pap smears (CS) and liquid-based cytology preparations (LBC). STUDY DESIGN: Follow-up information for all atypical glandular cells of undetermined significance (AGUS)/ AGC cases encountered in Queen Mary Hospital from July 2000 to June 2004 was analyzed. The difference in percentages associated with certain end points when using different reporting systems and preparation methods were compared. The age trends and time interval between cytologic diagnosis and detection of positive end points were studied. RESULTS: More than half of these cases turned out to be "negative." The majority with "negative" end points belonged to the "not otherwise specified" (NOS) groups (including atypical endometrial cells) in TBS 2001. The connotation of "favor neoplastic" carried a high positive predictive value for significant lesions. Most of the significant outcomes were discovered within the subsequent 6 months. A decreased reporting of "AGC, NOS" and an increased reporting of "atypical endocervical cells, NOS" were noted when using LBC. CONCLUSION: Subcategorization of AGC in TBS 2001 according to cellular origin and risk of malignancy, which is further enhanced by application of LBC, is useful.

Fine needle aspiration cytology of invasive micropapillary carcinoma of the breast.

AIM: To determine the pathognomonic diagnostic cytological features of invasive micropapillary carcinoma of the breast which is a poor prognostic subtype of infiltrating ductal carcinoma. METHODS: A series of 20 histologically proven tumours were reviewed retrospectively to evaluate the various cytological features, including tumour morules, isolated malignant cells, staghorn epithelial structures, mucinous background and apocrine metaplasia. RESULTS: Tumour morules formation and isolated malignant cells were the two most reliable and constant cytological features, being present in 75% (15/20 cases) of cases. Staghorn epithelial structures were present in 35% (7 cases). Mucinous background (2 cases, 10%) and apocrine metaplasia (4 cases, 20%) of the tumour cells were seen in a few cases only and did not appear very helpful. CONCLUSION: Tumour morules formation, isolated malignant cells and staghorn epithelial structures are the most reliable cytological features, and the presence of these should raise suspicion of invasive micropapillary carcinoma.

Fine needle aspiration cytology in follicular dendritic cell sarcoma: a report of two cases.

BACKGROUND: Since the first description of extranodalfollicular dendritic cell sarcoma in 1994, there has been a gradual increase in understanding of the morphologic features and clinical presentation of this tumor. However, difficulties persist in making cytologic diagnosis. CASES: Two cases of follicular dendritic cell sarcoma with fine needle aspiration cytology (FNAC) findings were reported. The first patient was a Chinese woman who presented with a right tonsillar mass, which was followed by right submandibular recurrence. The second patient was a Chinese man with known history of Castleman's disease of the nasopharynx complicated by follicular dendritic cell sarcoma, followed by tumor recurrence in cervical lymph nodes. FNAC of both recurrent cases showed isolated or syncytial sheets of tumor cells containing eosinophilic granular cytoplasm, ill-defined cell borders, round to oval nuclei, solitary round eosinophilic nucleoli and fine chromatin. CONCLUSION: The tumor cells in follicular dendritic cell sarcoma show cytologic features reminiscent of native follicular dendritic cells but with a greater than expected cell number and nuclear pleomorphism. These cells may be immunohistochemically inert for follicular dendritic cell markers CD21 and CD35. A presumptive diagnosis on the basis of cytologic examination is possible when paying attention to the subtle morphologic features.

A follow-up study of atypical squamous cells in gynecologic cytology using conventional papanicolaou smears and liquid-based preparations: the impact of the Bethesda System 2001.

We evaluated the impact of the Bethesda System (TBS) 2001 in cytology reporting of atypical squamous cells (ASC) when using conventional Pap smears and liquid-based cytology preparations (LBC). Follow-up information for all ASC cases encountered in Queen Mary Hospital, Hong Kong, China, from July 2000 to June 2004 (using TBS 1991 in the first 2-year period and TBS 2001 in the second) was analyzed. Among 4, 089 ASC cases studied, more than 50% had negative follow-up; this percentage was lower with TBS 2001. The percentage of ASC cases with a low-grade cervical intraepithelial neoplasia (CIN) end point was higher with TBS 2001, especially after application of LBC. There was also a decreasing trend of having this low-grade CIN end point with advancing age. Most clinically significant outcomes occurred after 6 months and before 1 year post-ASC diagnosis. With TBS 2001, more than 50% of ASC, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) were associated with high-grade CIN on follow-up. TBS 2001 improves the positive predictive value of ASC for clinically significant lesions. Introduction of dichotomous subcategorization of ASC is relevant, with ASC-H associated with a much higher risk of subsequent high-grade squamous lesions.

Toward implementation of a regional quality assurance program in cytopathology: the Hong Kong experience.

OBJECTIVE: To develop a local quality assurance program in cytopathology based on circulation of patient specimens on glass slides, with limited resources. STUDY DESIGN: A working group was set up for design and running of the program. Participation is on a laboratory basis. The scope and frequency of testing are defined. Well-documented cases (including gynecologic, nongynecologic and fine needle aspiration cytology) with commonly encountered diagnoses are collected. Consensus concerning the diagnosis, interpretive menu and scoring system is sought before the actual slide circulations using express mail. After returning their answers to the program organizer, the participating laboratories receive immediate feedback on their scores, with reference answers, explanatory notes, "whole-mount" images of glass slides and cumulative responses of peer laboratories for on-site checking. At the end of each year, an electronic file containing representative photomicrographs of all cases examined is provided to individual laboratories for their permanent records and training purposes. RESULTS: The program was launched in mid-2003. There were 24 and 27 participating laboratories from Hong Kong (and Macau) in 2003 and 2004, respectively. To date, >150 well-documented cytology cases are available in the slide pool and ready for circulation. As the revenue is mainly to cover the expenses of express mail, the program can be carried out at a relatively low cost. CONCLUSION: In order to have any cytology quality assurance program accepted by local laboratories, it has to be fair and practical. Strict confidentiality needs to be observed throughout the process. This program emphasizes both performance assessment and educational value. Adequate representation from experienced local cytology workers, detailed documentation support from authorities and assistance from dedicated staff are essential to the success of any external proficiency testing scheme. Regular review and evaluation are also necessary for continuous improvement. The Hong Kong experience can serve as an example of running a glass slide-based cytology quality assurance program in a small region with limited resources.

Liquid-based cytology findings of glassy cell carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis.

BACKGROUND: Glassy cell carcinoma is a rare form of poorly differentiated carcinoma of the cervix with no obvious squamous or glandular differentiation. Its liquid-based cytology findings have not been described before. CASE: A 46-year-old Filipina presented with vaginal bleeding due to a bulky cervical tumor. The liquid-based cytology preparation was of moderate cellularity and contained small clusters of polygonal to elongated tumor cells admixed with amphophilic, granular, necrotic debris. The malignant cells possessed round to oval nuclei; a thin nuclear membrane; finely dispersed chromatin; prominent, solitary nucleoli; abundant, cyanophilic cytoplasm; and discrete cell borders. Occasional tumor cells showed phagocytosis of polymorphs. The background contained a mixed population of inflammatory cells. Eosinophils, though present, were not readily identified in the cytologic specimen. There was no evidence of dyskeratosis, cytoplasmic vacuolation or koilocytosis. Histologic and ultrastructural examination of the tumor biopsy showed classic features of glassy cell carcinoma. Molecular analysis using polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus (HPV) DNA in the liquid-based cytology sample. The HPV genotype, however, did not belong to any of the commonly encountered prototypes. CONCLUSION: Glassy cell carcinoma of the cervix may show distinct, though subtle, cytomorphologic features in liquid-based preparations. The findings, however, are slightly different from those in conventional cervical smears. Awareness of this rare entity is important, as glassy cell carcinoma is often associated with more aggressive clinical behavior.

Mammary mucinous carcinoma with marked cytoplasmic hyalinization. A report of 2 cases with emphasis on fine needle aspiration cytologic findings.

BACKGROUND: Cytoplasmic eosinophilia in breast tumors is due mainly to abundance of secretory granules, lysosomes and/or mitochondria. Diffuse cytoplasmic hyalinization caused by intermediate filaments has not been described before. CASES: Two cases of pure mammary mucinous carcinoma occurred with marked cytoplasmic hyalinization among 556 wide excision/mastectomy specimens of mammary ductal carcinoma, either in situ or invasive, encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the period from 1994 to the end of 2001. Preoperative fine needle aspiration cytology was available in 1 case, showing cohesive clusters and micropapillae of tumor cells in abundant background mucin. The tumor cells had low mitotic activity and possessed round to oval nuclei, solitary macronucleoli; ample, eosinophilic cytoplasm and discrete cell borders. Cytoplasmic granularity, intracytoplasmic vacuoles or "cometlike" cells were not found. Histologic examination of the surgical specimens in both cases revealed pure mucinous carcinoma with diffuse and marked cytoplasmic hyalinization. There was no evidence of peritumoral lymphovascular permeation or regional lymph node metastasis. Ultrastructural examination showed minimal secretory activity, with abundant, loose aggregates of intermediate filaments in the cytoplasm. There was a relative paucity of other organelles. CONCLUSION: Diffuse cytoplasmic hyalinization is a peculiar morphologic change in mammary ductal carcinoma and apparently unique to pure mucinous carcinoma. Recognition of this phenomenon may help to avoid misdiagnosis of other types of ductal carcinoma with cytoplasmic eosinophilia, such as apocrine carcinoma and ductal carcinoma with neuroendocrine differentiation, which sometimes are also associated with pools of extracellular mucin.

Nodal presentation of nasal-type NK/T-cell lymphoma. Report of two cases with fine needle aspiration cytology findings.

BACKGROUND: Epstein-Barr virus (EBV)-associated NK/T-cell lymphoma typically occurs in extranodal sites, such as nasal cavity, nasopharynx, gastrointestinal tract, skin, testis and salivary gland. Secondary lymph node involvement is rarely encountered until late in the disease course. The fine needle aspiration cytology of NK/T-cell lymphoma with a nodal presentation has not been described before. CASES: Two cases of nasal-type (extranasal) NK/T-cell lymphoma with a nodal presentation were seen at Pamela Youde Nethersole Eastern Hospital, Hong Kong. Both patients presented with submandibular lymph node enlargement but unremarkable peripheral blood and bone marrow findings. Fine needle aspiration cytology was available in both cases, showing a heterogeneous population of small to medium-sized lymphoid cells, follicular center cells, plasma cells, eosinophils and some histiocytes. The medium-sized lymphoid cells showed readily discernible nuclear atypia with an irregular nuclear outline. Cell block sections revealed occasional lymphoid cells with pleomorphic nuclei. Immunocytochemical study confirmed the presence of CD56-positive lymphoma cells. In situ hybridization for EBV-encoded RNA also revealed positive nuclear signals. Histologic examination of the surgical biopsies showed interfollicular expansion by malignant lymphoid cells. Immunoglobulin heavy chain gene and T-cell receptor gene rearrangement studies demonstrated a germline pattern, confirming the putative NK (natural killer cell), non-B and non-T lineage of the lymphoma cells. CONCLUSION: Nodal presentation of NK/T-cell lymphoma, though rare, is diagnosable on the basis of fine needle aspiration biopsy alone, especially in view of its distinctive immunophenotype and EBV association. Recognition of the subtle but definite cytologic atypia of malignant lymphoid cells and presence of an appropriate background (including more eosinophils than usual), together with proper application of ancillary techniques, is crucial to arriving at a correct diagnosis.

Thin-layer cytology findings of papillary adenosquamous carcinoma of the cervix. Report of a case with histologic correlation and molecular analysis.

BACKGROUND: Papillary squamotransitional cell carcinoma of the lower female genital tract is a rare form of malignancy with distinctive histologic features. To my knowledge, its adenosquamous counterpart has not been reported before. CASE: A 69-year-old woman presented with postmenopausal bleeding due to a bulky cervical tumor. The thin-layer cytology preparation (Autocyte, TriPath Imaging, Burlington, North Carolina, U.S.A.) was of high cellularity and contained multiple small, papillary clusters of basaloid to columnar cells. Discernible fibrovascular cores were noted. In the background were many loosely dispersed, bland-looking columnar cells as well as cells of high grade squamous intraepithelial lesion (CIN 3). On a diligent search, scattered adenocarcinoma cells containing distinct intracytoplasmic vacuoles were found. There were a small number of dyskaryotic squamous cells with bizarre shapes, assuming "tadpolelike" morphology. Histologic examination of the tumor biopsy showed a papillary tumor with central fibrovascular cores covered with mitotically active, poorly differentiated squamous cells that imperceptibly merged with abortive glandular structures. Molecular analysis using the polymerase chain reaction and restriction fragment length polymorphism revealed the presence of human papillomavirus type 16 DNA in the liquid-based cytology sample. CONCLUSION: Papillary adenosquamous carcinoma of the cervix shares some morphologic and even histogenetic overlaps with papillary squamotransitional cell carcinoma and, to a lesser extent, conventional endocervical adenocarcinoma. It may pose certain diagnostic dilemmas for the unwary. In view of its distinctive cytohistologic features, this tumor warrants greater recognition in gynecologic pathology.

Mammary pseudoangiomatous stromal hyperplasia. A reappraisal of the fine needle aspiration cytology findings.

OBJECTIVE: To describe and reevaluate the fine needle aspiration cytology findings of pseudoangiomatous stromal hyperplasia (PASH) of the breast, with histologic, immunohistochemical and ultrastructural correlation. STUDY DESIGN: The authors reviewed the clinical features, fine needle aspiration cytology, histology and immunohistochemical results in all cases of mammary PASH encountered at Pamela Youde Nethersole Eastern Hospital, Hong Kong, during the 4-year period from January 1998 to May 2002. Ultrastructural examination was carried out in a selected example. The findings were compared with those in the literature. RESULTS: Four cases of PASH of the breast were encountered during the study period. The ages of the patients ranged from 34 to 56 years. One of them was a male presenting with gynecomastia. Only 2 cases had fine needle aspiration biopsies with a satisfactory cellular yield available for review. The cytospin preparations were of moderate cellularity and showed cohesive clusters of bland-looking ductal cells in a background of single, naked nuclei and some spindle cells containing fine chromatin and a discernible amount of cytoplasm. Occasional ductal cell clusters assuming a "staghorn" pattern, a feature commonly seen in fibroadenoma, were noted. Besides, there were scantly, loose and hypocellular stromal tissue fragments that contained spindle cells and occasional paired, elongated nuclei embedded in a fibrillary matrix. Histologic examination of the excisional biopsies confirmed the presence of PASH. It was characterized by many slitlike spaces rimmed by CD34-positive myofibroblasts/fibroblasts in a focally hyalinized stroma. Sometimes, ill-formed, fusiform aggregates of fibroblasts were also observed. Their fibroblastic nature was confirmed by electron microscopy. CONCLUSION: Fine needle aspiration cytology of PASH closely resembles that of fibroadenoma. Though subtle differences do exist, a definitive diagnosis is unlikely on the basis of the cytologic examination alone. PASH needs to be distinguished from borderline lesions, such as phyllodes tumor, and more sinister conditions, which sometimes have a similar cytologic appearance.