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.

Mucosal Schwann Cell Hamartoma in Colorectal Mucosa: A Rare Benign Lesion That Resembles Gastrointestinal Neuroma

No abstract available.

An unusual case of metachronous NK/T cell lymphoma and interdigitating dendritic cell sarcoma

No abstract available.

Necrotizing Sarcoid Granulomatosis: Possibly Veiled Disease in Endemic Area of Mycobacterial Infection

No abstract available.

Nodal involvement of extranodal marginal zone lymphoma with extreme plasmacytic differentiation (Mott cell formation) simulating plasma cell neoplasm and lymphoplasmacytic lymphoma

No abstract available.

Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival

BACKGROUND: The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. METHODS: Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. RESULTS: The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012). CONCLUSIONS: Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker.

Cytological Evaluation and REBA HPV-ID HPV Testing of Newly Developed Liquid-Based Cytology, EASYPREP: Comparison with SurePath

BACKGROUND: The objective of this study was to evaluate a newly-developed EASYPREP liquid-based cytology method in cervicovaginal specimens and compare it with SurePath. METHODS: Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens. RESULTS: EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis. CONCLUSIONS: EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping.

Fine Needle Aspiration Cytology of Thyroid Follicular Neoplasm: Cytohistologic Correlation and Accuracy

BACKGROUND: This study evaluated the accuracy of fine needle aspiration cytology (FNAC) in cases of follicular neoplasm (FN) on the basis of histologic diagnosis, and reviewed the cytologic findings of FN according to the FNAC. METHODS: Among the 66 cases diagnosed with thyroid FN by FNAC during the 7-year period from 2003 to 2009, 36 cases that had undergone thyroid surgery were available for review. Cytologic diagnosis was compared with the histologic diagnosis of each case. RESULTS: Among the 36 cases with a cytologic diagnosis of thyroid FN, histologic diagnosis was as follows: 20 follicular adenomas (55.6%), 3 Hurthle cell adenomas (8.3%), 2 follicular carcinomas (5.6%), 8 nodular goiters (22.2%), 2 papillary carcinomas (5.6%), and 1 Hashimoto's thyroiditis (2.8%), resulting in a diagnostic accuracy of FNAC for thyroid FN of 69.5%. CONCLUSIONS: This study shows that FNAC for thyroid FN is a useful primary screening method because when FN is diagnosed by FNAC, the rate of FN histologic diagnosis is relatively high, however, adequate sampling and experience is a prerequisite for this procedure.

Pathophysiology of Gastric MALT Lymphoma / 대한내과학회지

Early gastric mucosa-associated lymphoid tissue (MALT) lymphoma is considered as an antigen-dependent disease associated with long standing antigenic stimulation by Helicobacter pylori (H. pylori) which induces chronic immune response and lymphoid tissue development at the gastric mucosa normally devoid of lymphoid tissue. With disease progression, antigen-independent clones occur via genetic alterations inducing aberrant activation of nuclear factor kappaB (NF-kappaB) pathway which is essential for regulation of normal lymphocyte development and activation. Four major translocations, including t (11;18)/API2-MALT1, t (1;14)/BCL10-IGH, t (14;18)/(IGH-MALT1 and t (3;14)/FOXP1-IGH, occur mutually exclusively and lead to generation of cIAP2-MALT1 fusion protein or overexpression of BCL10, MALT1 and Foxp1. Translocation t (3;14)(q27;q32)/BCL6-IGH and t (1;2)(p22;p12)/BCL10-IGkappaL also occur in some MALT lymphomas. Mutational inactivation of A20, global NF-kappaB inhibitor, involve the development of especially translocation-negative MALT lymphoma. Downstream effects of most genetic alteration converge on the same NF-kappaB mediated oncogenic pathway. This review discusses the current advances in the pathophysiology underlying the development of gastric MALT lymphoma and its progression.

Immunohistochemical Expression of DCUN1D1 in Non-small Cell Lung Carcinoma: Its Relation to Brain Metastasis / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Non-small cell lung carcinoma (NSCLC) comprises 75-85% of all lung cancers, and approximately 25% of all NSCLC patients develop brain metastasis. There are no reliable markers for predicting in which patients this metastasis will occur. DCUN1D1, also known as squamous cell carcinoma-related oncogene, is associated with tumor progression and poor outcomes in NSCLC. The objective of this study was to investigate the role of DCUN1D1 expression in cases of brain metastasis due to NSCLC. MATERIALS AND METHODS: Primary tumor samples from a total of 71 cases of NSCLC, either with (n=40) or without (n=31) brain metastasis, were evaluated for DCUN1D1 expression by immunohistochemistry analysis. RESULTS: DCUN1D1 expression was detected in 16 patients (23%) and tended to correlate with T classification (15% of T1-2 tumors vs. 30% of T3-4 tumors, p=0.083). DCUN1D1 expression was significantly associated with tumor stage. It was observed in none of the patients with stage I disease, 10% of those with stage II disease, and 29% with stage III disease (p=0.009). In addition, 14 of 16 DCUN1D1-positive patients resulted in brain metastasis (p=0.01). The odds ratio of brain metastasis for patients with DCUN1D1 expression was 3.112 (p=0.009). CONCLUSION: DCUN1D1 expression may play a role in tumor progression and development of brain metastasis in patients with NSCLC. Evaluation of DCUN1D1 expression may provide assistance in identifying those patients who are at higher risk for brain metastasis.

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II)

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Proposal for Creating a Guideline for Cancer Registration of Microinvasive Tumors of the Breast and Ovary (II)

BACKGROUND: Cancer registration in Korea has a longer than 30-years of history, during which time cancer registration has improved and become well-organized. Cancer registries are fundamental for cancer control and multi-center collaborative research. However, there have been discrepancies in assigning behavior codes. Thus, we intend to propose appropriate behavior codes for the International Classification of Disease Oncology, 3rd edition (ICD-O-3) for microinvasive tumors of the ovary and breast not only to improve the quality of the cancer registry but also to prevent conflicts. METHODS: As in series I, two pathology study groups and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated. To prepare a questionnaire on provisional behavior code, the relevant subjects were discussed in the workshop, and consensus was obtained by convergence of opinion from members of KSP. RESULTS: Microinvasive tumor of the breast should be designated as a microinvasive carcinoma which was proposed as malignant tumor (/3). Serous borderline tumor with microinvasion of the ovary was proposed as borderline tumor (/1), and mucinous borderline tumor with microinvasion of the ovary as either borderline (/1) or carcinoma (/3) according to the tumor cell nature. CONCLUSIONS: Some issues should be elucidated with the accumulation of more experience and knowledge. Here, however, we present our second proposal.

Prognostic Significance of High Expression of ER-beta in Surgically Treated ER-Positive Breast Cancer Following Endocrine Therapy / 한국유방암학회지

PURPOSE: This study evaluated estrogen receptor (ER)-beta mRNA and ER-beta protein expression and its prognostic implications in hormone receptor-positive breast cancer. METHODS: Paraffin sections from 139 hormone receptor-positive breast cancer cases were prepared. The expression of ER-beta mRNA and protein were analyzed by branched-chain assay and immunohistochemistry (IHC), respectively. RESULTS: The Allred score of ER-beta IHC was correlated with smaller tumor size (p=0.043), the Allred score of ER-alpha IHC (p<0.001), and the Allred score of progesterone receptor (PR) IHC (p=0.022) but not with the HER2 IHC score. ER-beta mRNA level was correlated with PR mRNA levels (p<0.001) but not with the Allred score of ER-beta IHC, ER-alpha IHC, and PR IHC, nor with the HER2 IHC score and ER-alpha mRNA level. In survival analysis, high expression of ER-beta mRNA was associated with worse disease-free survival along with poor differentiation, lymph node metastasis and absence of PR protein expression in univariate analysis (p=0.040, p=0.002, p=0.018, and p=0.007, respectively) and multivariate analysis (p=0.044, p=0.002, p=0.035, and p=0.007, respectively). CONCLUSION: High expression of ER-beta mRNA is an independent predictor of disease recurrence in hormone-receptor-positive breast cancer.

Expression of Human Papillomavirus-Related Proteins and Its Clinical Implication in Tonsillar Squamous Cell Carcinoma

BACKGROUND: Human papillomavirus (HPV) is known to cause of oropharyngeal squamous cell carcinoma (SqCC). HPV positive SqCCs overexpress p16 and are associated with better survival. Several markers of cell cycles and apoptosis have been reported as a prognostic value. We examined the prognostic value of HPV status, p16, cyclin D1, and Bcl-2 in patients with tonsillar SqCC. METHODS: Tissue microarrays were constructed in 56 cases of tonsillar SqCC for which we performed an immunohistochemistry and an in situ hybridization (ISH) of the HPV. RESULTS: Of the 56 cases, 31 (55.3%) were positive for p16 and 20 (35.7%) were positive for HPV ISH. The expressions of p16, cyclin D1, and Bcl-2 were not correlated with the clinicopathologic variables including smoking status, differentiation and pT- and pN-stages. The HPV ISH positive group showed a better overall survival than the HPV negative group (p=0.04), and the p16 positive group showed a better disease free survival (DFS) than the negative group (p=0.016). Cox regression analysis showed that only p16 positivity was an independent prognostic factor for DFS (p=0.03; hazard ratio, 10.1). CONCLUSIONS: Our results indicate that both p16 expression and HPV status are useful indicators for risk stratification in patients with tonsillar SqCC.

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.

Molecular Genetic Approach of Gastric MALT Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is a common low grade B-cell lymphoma arising from a background of chronic inflammatory disease at a number of mucosal sites. The association between Helicobacter pylori and gastric MALT lymphoma is well known and it appears that H. pylori is critical for lymphomagenesis and also creates a microenvironment favoring the growth of neoplastic B cells. The understanding of MALT lymphoma biology has significantly improved, and at least 4 recurrent translocations t(11;18)/API2-MALT1, t(1;14)/IGH-BCL10, t(14;18)/IGH-MALT1 and t(3;14)/IGH-FOXP1 have been implicated in the pathogenesis of MALT lymphoma. Here, we review the recent advances in association of microorganisms with MALT lymphoma and the molecular genetics underlying the lymphoma development.

Primary Acinic Cell Carcinoma of the Breast: A Case Report with an Immunohistochemical and Ultrastructural Studies / 한국유방암학회지

Acinic cell carcinoma (ACC) of the breast is extremely rare and is characterized by widespread acinar cell-like differentiation. We report of a 39-year-old woman presented with a palpable breast mass with significant morphological, immunohistochemical and ultrastructural findings. Histologically, ACC showed a diffuse glandular infiltrative pattern, with small acinar or glandular structures mixed with solid nests. Neoplastic cells were monotonous proliferation of cells with a granular or clear cytoplasm, resembling acinar cells of the salivary glands or Paneth cells. Both glandular and solid tumor cell populations were strongly positive for lysozyme and alpha-1-antitrypsin.

Systemic Plasmacytosis: A Case Report with a Review of the Literature

Systemic plasmacytosis is an uncommon disorder characterized by widely disseminated macular skin eruptions composed of polyclonal lymphoplasmacytic infiltrates associated with variable extracutaneous involvement. An aggressive clinical course has been observed in a small number of patients, but most cases have followed chronic and benign clinical course without spontaneous remission. Previously reported cases of this entity have been described almost exclusively in Japanese patients. We recently experienced a case of systemic plasmacytosis in a 48-year-old Korean female patient. Initial skin biopsy specimen revealed patchy perivascular and periadnexal infiltrates of mature plasma cells. Serum immunoelectrophoresis revealed polyclonal hypergammaglobulinemia, and polyclonal plasmacytosis was noted on the subsequent biopsy specimens of left supraclavicular and axillary lymph nodes. Multiple tiny pulmonary nodules appeared six years after the initial cutaneous presentation and were found to be of the same histologic appearance. We herein report a rare case of systemic plasmacytosis with a review of the literature.

Prognostic Significance of Amplification of the c-MYC Gene in Surgically Treated Stage IB-IIB Cervical Cancer

BACKGROUND: Mutations of c-MYC have been described in cervical cancer. However, association between c-MYC gene status and its prognostic significance have not been clarified. METHODS: Tissue microarray sections from 144 patients with stage IB-IIB cervical cancer treated by radical hysterectomy were analyzed by fluorescence in situ hybridization using a region-specific probe for c-MYC and a centromere-specific probe for chromosome 8. RESULTS: Seventy five percent (108/144) of c-MYC gain and 6.9% (10/144) of c-MYC gene amplification were observed. c-MYC gene alteration was more frequently observed in squamous cell carcinoma than adenocarcinoma or adenosquamous carcinoma and were associated with low Ki67 labeling index (p=0.013). c-MYC amplification was not associated with clinicopathologic parameters except absence of bcl2 expression (p=0.048). Survival analysis revealed that patients with c-MYC amplification were significantly associated with higher risk of disease recurrence (p=0.007) and cancer related death (p=0.020). However, c-MYC gain was not associated with unfavorable outcome. Multivariate analysis proved c-MYC amplification as independent prognostic factors of shorter disease free survival and cancer-related death (p=0.028 and p=0.025, respectively). CONCLUSIONS: c-MYC amplification, not gain, is an independent prognostic marker for shorter disease free and cancer specific survival in cervical cancer treated by radical hysterectomy.

Detection Limit of Monoclonal B-Cells Using Multiplex PCR and Laser-Induced Fluorescence Capillary Electrophoresis

BACKGROUND: The identification of monoclonality has been widely used for making diagnoses of lymphoproliferative lesions. Awareness of the sensitivity and detection limit of the technique used would be important for the data to be convincing. METHODS: We investigated the minimum requirement of cells and sensitivity of gel electrophoresis (GE) and laser-induced fluorescence capillary electrophoresis (LFCE) for identifying IgH gene rearrangement using BIOMED-2 protocols. DNA extracted from Raji cells were diluted serially with peripheral blood mononuclear cells (PBMNCs) DNA. DNA from mixtures of diffuse large B-cell lymphoma (DLBCL) and reactive lymph nodes were also serially diluted. RESULTS: For Raji cells, the detection limit was 62 and 16 cell-equivalents for GE and LFCE, respectively. In the condition with PBMNCs mixture, 2.5% and 1.25% of clonal cells was the minimum requirement for GE and LFCE, respectively. In 23% of DLBCL cells in tissue section, the detection limit was 120 and 12 cell-equivalents for GE and LFCE, respectively. In 3.2% of DLBCL cells, that was 1,200 and 120 cell-equivalents for GE and LFCE, respectively. CONCLUSIONS: These results show that LFCE method is more sensitive than GE and the sensitivity of clonality detection can be influenced by the amount of admixed normal lymphoid cells.