A stepwise approach to fine needle aspiration cytology of lymph nodes

The cytological diagnosis of lymph node lesions is extremely challenging because of the diverse diseases that cause lymph node enlargement, including both benign and malignant or metastatic lymphoid lesions. Furthermore, the cytological findings of different lesions often resemble one another. A stepwise diagnostic approach is essential for a comprehensive diagnosis that combines: clinical findings, including age, sex, site, multiplicity, and ultrasonography findings; low-power reactive, metastatic, and lymphoma patterns; high-power population patterns, including two populations of continuous range, small monotonous pattern and large monotonous pattern; and disease-specific diagnostic clues including granulomas and lymphoglandular granules. It is also important to remember the histological features of each diagnostic category that are common in lymph node cytology and to compare them with cytological findings. It is also essential to identify a few categories of diagnostic pitfalls that often resemble lymphomas and easily lead to misdiagnosis, particularly in malignant small round cell tumors, poorly differentiated squamous cell carcinomas, and nasopharyngeal undifferentiated carcinoma. Herein, we review a stepwise approach for fine needle aspiration cytology of lymphoid diseases and suggest a diagnostic algorithm that uses this approach and the Sydney classification system.

Efficacy of Brentuximab Vedotin in Relapsed or RefractoryHigh-CD30–Expressing Non-Hodgkin Lymphomas:Results of a Multicenter, Open-Labeled Phase II Trial / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expressionin previous studies enrolling patients with a wide range of CD30 expression level.Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma(NHL) patients most likely to benefit. @*Materials and Methods@#This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks.The primary endpoint was > 40% disease control rate, consisting of complete response(CR), partial response (PR), or stable disease. We defined high CD30 expression as ! 30%tumor cells positive for CD30 by immunohistochemistry. @*Results@#High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma.The disease control rate was 48.5% (16/33) including six CR and six PR; six patients(4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survivalwere not associated with CD30 expression levels. Over a median of 29.2 months offollow-up, the median progression-free and overall survival rates were 1.9 months and 6.1months, respectively. The most common adverse events were fever (39%), neutropenia(30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis forthe association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1-negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients(13.3%, 2/15). @*Conclusion@#BV performance as a single agent was acceptable in terms of disease control rates and toxicityprofiles, especially MUM1-negative patients.

Cytological Features That Differentiate Follicular Neoplasm from Mimicking Lesions

BACKGROUND: It is difficult to correctly diagnose follicular neoplasms (FNs) on fine-needle aspiration cytology (FNAC) because it shares many cytological features with other mimicking lesions. The aim of this study was to identify the cytological features that differentiate FNs from mimicking lesions. METHODS: We included the cytological slides from 116 cases of thyroid FN diagnosed on FNAC, and included their subsequent histological diagnoses. We evaluated the cytological architectural pattern and nuclear features of the lesions according to their histological groups. RESULTS: The final histological diagnoses of the 116 cases varied, and included 51 FNs (44%), 47 papillary thyroid carcinomas (40%) including follicular variant, and seventeen cellular nodular hyperplasias (15%). Regardless of the final histological diagnosis, microfollicular pattern was observed in most cases. On the other hand, trabecular pattern was identified in 34% of FNs, but not in any other lesions. Additionally, elongated nuclei and ground glass chromatin were found in only some papillary thyroid carcinomas. CONCLUSIONS: This study shows that the trabecular pattern is a representative cytological feature of FNs that can be used to distinguish FNs from mimicking lesions. In addition, nuclear shape and chromatin pattern can be used to further confirm the diagnosis of FNs from mimicking lesions through FNAC.

Importance of Individual Ghost Cells in Fine-Needle Aspiration Cytology Diagnosis of Pilomatricoma

BACKGROUND: Although histological diagnosis of pilomatricoma is not difficult because of its unique histological features, cytological diagnosis through fine-needle aspiration cytology (FNAC) is often problematic due to misdiagnoses as malignancy. METHODS: We reviewed the cytological features of 14 cases of histologically-proven pilomatricoma from Korea Cancer Center Hospital, with a discussion on the diagnostic pitfalls of FNAC. RESULTS: Among 14 cases of pilomatricoma, 10 (71.4%) were correctly diagnosed through FNAC, and two (14.3%) were misdiagnosed as carcinoma. Cytologically, all cases had easily recognizable clusters of basaloid cells and foreign body-type multinucleated cells. Although ghost cells were also found in all cases, some were inconspicuous and hardly recognizable due to their small numbers. CONCLUSIONS: An accurate diagnosis of pilomatricoma in FNAC is feasible with consideration of clinical information and close examination of ghost cells.

Epstein-Barr Virus–Associated Lymphoproliferative Disorders: Review and Update on 2016 WHO Classification

Epstein-Barr virus (human herpesvirus-4) is very common virus that can be detected in more than 95% of the human population. Most people are asymptomatic and live their entire lives in a chronically infected state (IgG positive). However, in some populations, the Epstein-Barr virus (EBV) has been involved in the occurrence of a wide range of B-cell lymphoproliferative disorders (LPDs), including Burkitt lymphoma, classic Hodgkin’s lymphoma, and immune–deficiency associated LPDs (post-transplant and human immunodeficiency virus–associated LPDs). T-cell LPDs have been reported to be associated with EBV with a subset of peripheral T-cell lymphomas, angioimmunoblastic T-cell lymphomas, extranodal nasal natural killer/T-cell lymphomas, and other rare histotypes. This article reviews the current evidence covering EBV-associated LPDs based on the 2016 classification of the World Health Organization. These LPD entities often pose diagnostic challenges, both clinically and pathologically, so it is important to understand their unique pathophysiology for correct diagnoses and optimal management.

Multifocal nodular lymphoid hyperplasia of the lung / 영남의대학술지

Nodular lymphoid hyperplasia (NLH) is a benign lymphoproliferative disease that can affect the lung. Because of its rarity, little is known about the etiology and natural history of NLH. Most cases are usually asymptomatic and found incidentally on imaging studies. Imaging finding of NLH has shown most commonly as a solitary lesion, although multifocal pulmonary nodules may be seen. Surgical resection has proved curative in the cases previously described. We report a rare case of NLH in a 55 year-old man who presented with bilateral multiple pulmonary nodules on chest radiography. Open biopsy was performed from the upper and lower lobe of the left lung. The lesions were pathologically diagnosed as pulmonary NLH. Multifocal residual nodules in both lungs remain stable without spontaneous regression during the 3 years of follow-up.

Multifocal nodular lymphoid hyperplasia of the lung / 영남의대학술지

Nodular lymphoid hyperplasia (NLH) is a benign lymphoproliferative disease that can affect the lung. Because of its rarity, little is known about the etiology and natural history of NLH. Most cases are usually asymptomatic and found incidentally on imaging studies. Imaging finding of NLH has shown most commonly as a solitary lesion, although multifocal pulmonary nodules may be seen. Surgical resection has proved curative in the cases previously described. We report a rare case of NLH in a 55 year-old man who presented with bilateral multiple pulmonary nodules on chest radiography. Open biopsy was performed from the upper and lower lobe of the left lung. The lesions were pathologically diagnosed as pulmonary NLH. Multifocal residual nodules in both lungs remain stable without spontaneous regression during the 3 years of follow-up.

Establishment of Hepatocellular Cancer Induced Pluripotent Stem Cells Using a Reprogramming Technique

BACKGROUND/AIMS: Cancer is known to be a disease by many factors. However, specific results of reprogramming by pluripotency-related transcription factors remain to be scarcely reported. Here, we verified potential effects of pluripotent-related genes in hepatocellular carcinoma cancer cells. METHODS: To better understand reprogramming of cancer cells in different genetic backgrounds, we used four liver cancer cell lines representing different states of p53 (HepG2, Hep3B, Huh7 and PLC). Retroviral-mediated introduction of reprogramming related genes (KLF4, Oct4, Sox2, and Myc) was used to induce the expression of proteins related to a pluripotent status in liver cancer cells. RESULTS: Hep3B cells (null p53) exhibited a higher efficiency of reprogramming in comparison to the other liver cancer cell lines. The reprogrammed Hep3B cells acquired similar characteristics to pluripotent stem cells. However, loss of stemness in Hep3B-iPCs was detected during continual passage. CONCLUSIONS: We demonstrated that reprogramming was achieved in tumor cells through retroviral induction of genes associated with reprogramming. Interestingly, the reprogrammed pluripotent cancer cells (iPCs) were very different from original cancer cells in terms of colony shape and expressed markers. The induction of pluripotency of liver cancer cells correlated with the status of p53, suggesting that different expression level of p53 in cancer cells may affect their reprogramming.

Therapeutic effect of topical application of curcumin during treatment of radiation burns in a mini-pig model

Curcumin protects the skin against radiation-induced epidermal damage and prevents morphological changes induced by irradiation skin, thereby maintaining the epidermal thickness and cell density of basal layers. In this study, the effects of topical curcumin treatment on radiation burns were evaluated in a mini-pig model. Histological and clinical changes were observed five weeks after radiation exposure to the back (⁶⁰Co gamma-radiation, 50 Gy). Curcumin was applied topically to irradiated skin (200 mg/cm²) twice a day for 35 days. Curcumin application decreased the epithelial desquamation after irradiation. Additionally, when compared to the vehicle-treated group, the curcumin-treated group showed reduced expression of cyclooxygenase-2 and nuclear factor-kappaB. Furthermore, irradiation prolonged healing of biopsy wounds in the exposed area, whereas curcumin treatment stimulated wound healing. These results suggest that curcumin can improve epithelial cell survival and recovery in the skin and therefore be used to treat radiation burns.

Is the Linear No-Threshold Dose-Response Paradigm Still Necessary for the Assessment of Health Effects of Low Dose Radiation?

Inevitable human exposure to ionizing radiation from man-made sources has been increased with the proceeding of human civilization and consequently public concerns focus on the possible risk to human health. Moreover, Fukushima nuclear power plant accidents after the 2011 East-Japan earthquake and tsunami has brought the great fear and anxiety for the exposure of radiation at low levels, even much lower levels similar to natural background. Health effects of low dose radiation less than 100 mSv have been debated whether they are beneficial or detrimental because sample sizes were not large enough to allow epidemiological detection of excess effects and there was lack of consistency among the available experimental data. We have reviewed an extensive literature on the low dose radiation effects in both radiation biology and epidemiology, and highlighted some of the controversies therein. This article could provide a reasonable view of utilizing radiation for human life and responding to the public questions about radiation risk. In addition, it suggests the necessity of integrated studies of radiobiology and epidemiology at the national level in order to collect more systematic and profound information about health effects of low dose radiation.

beta-irradiation (166Ho patch)-induced skin injury in mini-pigs: effects on NF-kappaB and COX-2 expression in the skin

In the present study, the detrimental effect of beta-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of beta-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after beta-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-kappaB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-kappaB and COX-2 play roles in epidermal cell regeneration following beta-irradiation of mini-pig skin.

Radiation-induced eosinophilic, polymorphic, and pruritic eruption in a pig skin model / 한국실험동물학회지

Eosinophilic, polymorphic and pruritic eruption associated with radiotherapy (EPPER) can occur in cancer patients after irradiation. In this study, we characterized the clinical and histopathological features of pig skin that developed widespread polymorphic and pruritic skin lesions following localized 50 Gy gamma-irradiation. The pigs developed pruritus 5-7 weeks after irradiation, and infiltration of the dermis by eosinophils was detected 4-7 weeks after irradiation. The irradiated animals also showed transiently increased numbers of peripheral eosinophils 5-7 weeks after treatment. Irradiation induced desquamation after 2-4 weeks, which and the desquamation gradually resolved after 7 weeks. These pathological changes correspond to those seen in irradiated human skin, indicating that this model could be useful for elucidating the pathogenesis of EPPER and for developing therapeutic and prophylactic methods.

A Case of Kikuchi Disease Involving an Intrapulmonary Lymph Node Mistaken for a Pulmonary Nodule / 대한내과학회지

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is an uncommon idiopathic, self-limiting disease characterized by cervical lymphadenopathy. Patients with KFD may present with a wide variety of nonspecific symptoms, including fever, night sweats, and weight loss. Although KFD can affect all lymph nodes of the body, involvement of the intrathoracic lymph nodes is relatively rare. In particular, isolated involvement of the intrapulmonary lymph nodes is extremely unusual. We herein report a case involving a 45-year-old man who presented with symptoms of myalgia, fatigue, and fever. Computed tomography performed during follow-up showed a slowly growing nodule in the upper lobe of the left lung. Results of laboratory tests did not reveal any evidence of infection or autoimmune disease, including systemic lupus erythematosus. Results of excisional biopsy by video-assisted thoracoscopic surgery revealed KFD in an intrapulmonary lymph node. His symptoms improved after a trial of nonsteroidal anti-inflammatory drugs.

Medullary Thyroid Carcinoma with Ectopic Adrenocorticotropic Hormone Syndrome

Ectopic adrenocorticotropic hormone (ACTH) syndrome is caused most frequently by a bronchial carcinoid tumor or by small cell lung cancer. Medullary thyroid carcinoma (MTC) is a rare etiology of ectopic ACTH syndrome. We describe a case of Cushing syndrome due to ectopic ACTH production from MTC in a 48-year-old male. He was diagnosed with MTC 14 years ago and underwent total thyroidectomy, cervical lymph node dissection and a series of metastasectomies. MTC was confirmed by the pathological examination of the thyroid and metastatic mediastinal lymph node tissues. Two years after his last surgery, he developed Cushingoid features, such as moon face and central obesity, accompanied by uncontrolled hypertension and new-onset diabetes. The laboratory results were compatible with ectopic ACTH syndrome. A bilateral adrenalectomy improved the clinical and laboratory findings that were associated with Cushing syndrome. This is the first confirmed case of ectopic ACTH syndrome caused by MTC in Korea.

Fine Needle Aspiration Cytology of Parathyroid Lesions

BACKGROUND: There has been an increase in the use of fine needle aspiration cytology (FNAC) for the diagnosis of parathyroid lesions (PLs). Differentiation between a thyroid lesion and a PL is not easy because of their similar features. We reviewed parathyroid aspirates in our institution and aimed to uncover trends in diagnostic criteria. METHODS: We selected 25 parathyroid aspirates (from 6 men and 19 women) confirmed surgically or immunohistochemically from 2006 to 2011. RESULTS: Major architectural findings of PLs include scattered naked nuclei, loose clusters, a papillary pattern with a fibrovascular core, tight clusters, and a follicular pattern. These architectures were commonly admixed with one another. Cytological features included anisokaryosis, stippled chromatin, a well-defined cell border, and oxyphilic cytoplasm. Eighteen of the 25 patients were diagnosed with PL using FNAC. Seven patients had been misdiagnosed with atypical cells (n=2), benign follicular cells (n=2), adenomatous goiter (n=2) and metastatic carcinoma (n=1) in FNAC. Using clinicoradiologic data, the sensitivity of the cytological diagnosis was 86.7%. The cytological sensitivity decreased to 50% without this information. CONCLUSIONS: FNAC of PL is easily confused with thyroid lesions. A combination of cytological parameters and clinical data will be required to improve the diagnostic sensitivity of PLs.

A Case of Hepatosplenic T-cell Lymphoma Diagnosed by Bone Marrow Examination

Hepatosplenic T-cell lymphoma (HSTL) is a condition in which lymphoma cells infiltrate the sinusoids of the liver, spleen, and bone marrow, without lymph node involvement. We encountered a case of hepatosplenic T-cell lymphoma in a Vietnamese woman. The patient was hospitalized with epigastric pain and nausea. Splenomegaly and multiple poorly defined, low-attenuating nodular lesions in the liver were visualized on computed tomography (CT), and thrombocytopenia was noted. The lymph nodes were not significantly enlarged. Splenic biopsy could not be performed because of severe thrombocytopenia. Neoplastic lymphoid cells were present in bone marrow aspirates. Bone marrow sections revealed infiltration of CD3(+) and CD20(-) neoplastic lymphoid cells in the sinusoids. A clonality assay (IdentiClone T-Cell Receptor Delta Gene Clonality Assay; Invivoscribe Technologies, USA) showed gene rearrangements in the T-cell receptor delta gene. Thus, we made a confirmatory diagnosis of HSTL. When splenic biopsy is not available, bone marrow aspirates and clonality assessment may become useful diagnostic tools.

Clinical characteristics and outcomes of primary bone lymphoma in Korea / 대한혈액학회지

BACKGROUND: This study evaluates the effectiveness of immunochemotherapy and radiation therapy in the treatment of patients with primary bone lymphoma (PBL). METHODS: We retrospectively reviewed the medical records of 33 patients with PBL who were treated at 6 medical centers in Korea from 1992 to 2010. Clinicopathological features and treatment outcomes were analyzed. RESULTS: The median age of the patients participating in our study was 40 years. The most common sites of involvement were the pelvis (12.36%) and femur (11.33%). CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) or CHOP-like regimens were administered to 20 patients (61%), and R-CHOP (rituximab plus CHOP) was administered to the remaining 13 patients (39%). The overall response rate was 89% (complete response, 76%; partial response, 12%). The overall survival (OS) of patients with solitary bone lesions was longer than that of patients with multiple bone lesions (median OS: not reached vs. 166 months, respectively; P=0.089). Addition of rituximab to CHOP did not significantly affect either OS or progression-free survival (P=0.53 and P=0.23, respectively). Combining radiation therapy with chemotherapy also did not improve the OS or progression-free survival of patients with solitary bone lesions. CONCLUSION: Conventional cytotoxic chemotherapy remains an effective treatment option for patients with PBL. Additional benefits of supplementing chemotherapy with either rituximab or radiation therapy were not observed in this study. Further investigation is needed to characterize the role of immunochemotherapy in treating patients with PBL.

An Adult Case of Severe Chronic Active Epstein-Barr Virus Infection with T-Cell Lymphoproliferative Disorder

No abstract available.

Fine-Needle Aspiration Cytology of Pleomorphic Carcinomas of the Lung

BACKGROUND: Pleomorphic carcinoma (PC) is a rare pulmonary malignancy. Because of its rarity and histological heterogeneity, cytopathologists might suspect PC only rarely on the basis of its cytological specimen. In addition, cytological findings from fine needle aspiration (FNA) specimens have rarely been described. Hence, we investigated the cytological features of FNA in the cases of PC. METHODS: We reviewed 7 FNA specimens of PC. The patients had undergone surgical resection at the Korea Cancer Center Hospital between 2007 and 2011. The cytological features of PC were assessed and compared with the histopathological features of the corresponding surgical specimen. Immunocytochemical analysis with cytokeratin and vimentin was performed on the cell blocks. RESULTS: The tumor cells were either dispersed or arranged in loose aggregates, and generally lacked any glandular or squamous differentiation. Pleomorphic or spindle shape tumor cells were observed, and mono-, bi-, or multi-nucleated giant cells were frequently observed. The background showed necrosis and contained numerous lymphocytes and neutrophils. Immunocytochemically, the tumor cells were positive for cytokeratin and vimentin. CONCLUSIONS: PC displays characteristic cytological features. It might therefore be possible to make an accurate diagnosis of PC by assessing the degree of nuclear atypia.

A Proposal for Creating a Guideline for Cancer Registration of the Fibromatosis, PEComa Group, Malignant Lymphoma In Situ and Dendritic Cell Tumors (III)

BACKGROUND: Understanding the biologic behavior of a tumor is a prerequisite for tumor registration code assignment. The aim of this report was to propose appropriate behavior codes of the International Classification of Disease Oncology 3 (ICD-O3) to rare, yet pathologically interesting hematopoietic and soft tissue tumors. METHODS: The Study Group for Hematopathology, the Bone and Soft Tissue Pathology Study Group, and the Cancer Registration Committee prepared the questionnaire containing provisional behavior codes of selected diseases. RESULTS: In situ lesions of mantle cell and follicular lymphomas, dendritic cell tumors, and neoplasms with perivascular epithelioid cell differentiation (PEComa), not otherwise specified were classified as malignant (-/3). The fibromatosis group, with the exception of lipofibromatosis, was proposed as benign (-/0). Lipofibromatosis and several diseases that belong to the PEComa group were proposed as uncertain malignant potential (-/1). For the hematologic and soft tissue tumors, 274 and 288 members of the Korean Society of Pathologists, respectively, provided opinions through questionnaire, and most responders showed agreement with the provisional behavior code proposed. CONCLUSIONS: The determination of behavior codes for the rare diseases described in this study, especially those of the PEComa group or malignant lymphoma, could be viewed as impractical and premature, but this study provides the basis for future research on this topic.