Rearrangement of anaplastic lymphoma kinase (ALK) gene is the best predictor of response to crizotinib, an ALK tyrosine kinase inhibitor. However, the prevalence of the ALK fusion is low, so accurate patient identification is crucial for successful treatment using ALK inhibitors. Furthermore, most patients with lung cancer present with advanced-stage disease at the time of diagnosis, so it is important for pathologists to detect ALK-rearranged patients while effectively maximizing small biopsy or cytology specimens. In this review, we propose a guideline recommendation for ALK testing approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.
Anaplastic lymphoma kinase; Gene rearrangement; Lung neoplasms; Guideline
Previous studies have suggested an association between usual interstitial pneumonia (UIP) and lung cancer (Ca). However, clinical and histological information is not enough to determine such an association, due to the low incidence and short survival time of patients with both conditions.
We retrospectively reviewed the clinical and histological records of Ca patients with UIP between January 1999 and August 2013 at the Samsung Medical Center, Seoul, Korea. We found 43 patients who had Ca with UIP (UIP-Ca). Previously reported data of eighty-four patients with UIP-only were included as a comparison group.
Smoking is related to poor prognosis in patients with UIP-Ca, and the number of patients with a high smoking index of more than 30 pack-years significantly increased in UIP-Ca patients compared with UIP-only patients. There is no significant prognostic differentiation between UIP-Ca patients and UIP-only patients. Microscopically, UIP-Ca patients showed characteristically heterogeneous histological patterns and degrees of differentiation. There were many foci of squamous metaplasia or dysplasia at the peripheral area of squamous cell carcinomas.
We report 43 cases of UIP-Ca. Our results suggest that smoking is related to cancer occurrence in UIP patients and poor prognosis in UIP-Ca patients.
Idiopathic pulmonary fibrosis; Lung neoplasms; Metaplasia; Smoking; Etiology; Survival
Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions.
Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]).
Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001).
This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.
Lung; Neuroendocrine tumors; PTEN; MicroRNA-21, human
This study investigates the prevalence of human papillomavirus (HPV) 52 and 58 genotypes among women residing in Busan, and the expression of p16 and p53 proteins in cervical neoplasia with HPV 52 and 58 infections.
A total of three hundred fifteen cases were analyzed using the HPV DNA chip test for HPV genotypes, and of these, we retrospectively examined p16 and p53 expression in 62 cases of cervical tissues infected with HPV 52 and 58 using immunohistochemistry.
HPV 52 and 58 genotypes were identified in 62 (54.9%) out of 113 high-risk, HPV-infected cases. Of the cases examined, there were 19 single HPV 52 infections (16.8%), 23 single HPV 58 infections (20.4%), 4 multiple HPV 52 infections (3.5%), and 16 multiple HPV-58 infections (14.2%). Immunoreactivity of p16 and p53 was observed in 41 (66.1%) and 23 (37.1%) of the 62 cases of cervical neoplasia infected with HPV 52 and 58 genotypes, respectively.
This study demonstrates a high prevalence of HPV 52 and 58 genotypes, in addition to HPV 16, among high-risk strains of cervical neoplasia in Korea. These findings suggest that development of more vaccines would be beneficial for the prevention of the various HPV genotypes.
HPV 52; HPV 58; Cyclin-dependent kinase inhibitor p16; Tumor suppressor protein p53; Cervical neoplasia
This study was aimed at investigating the relation of P2X7 receptor (P2X7R) expression with the clinicopathological features of papillary thyroid carcinoma (PTC) coexisting with Hashimoto's thyroiditis (HT).
We examined 170 patients (84, PTC with HT; 86, PTC without HT). P2X7R expression was examined by immunohistochemical methods. The staining intensity and patterns were evaluated and scored using a semi-quantitative method.
The PTC with HT group was more likely to contain women and had less extrathyroid extension, lymph node (LN) metastasis, lymphovascular invasion, and recurrence than the PTC without HT group. Patients positive for P2X7R had significantly higher frequencies of lymphovascular invasion, extrathyroid extension, LN metastasis, and absence of HT. As shown by multivariate analysis, the expression of P2X7R was significantly higher if HT was absent and extrathyroid extension was present. In the PTC with HT group, the expression of P2X7R was significantly higher in patients with tumor multifocality, lymphovascular invasion, and extrathyroid extension. In the PTC without HT group, the expression of P2X7R was significantly higher in women and those having tumor multifocality.
Coexistence of PTC with HT is associated with good prognostic factors, and P2X7R expression in PTC was correlated with poor prognostic factors and the absence of HT.
Hashimoto Disease; Thyroid cancer, papillary; Receptors, purinergic P2X7
Because of recent advances in the molecular diagnosis of cancer patients, tissue quality has become more important in daily practice.
To evaluate the effects of fixative, duration of fixation, decalcification, and storage periods on nucleic acid integrity, DNA and RNA were extracted from gastrointestinal cancer tissue. The yield and purity were analyzed, and polymerase chain reaction (PCR) for glyceraldehyde 3-phosphate dehydrogenase (GAPDH; 60 bp), β-actin (148 bp), and human growth hormone (hGH; 434 bp) and real-time reverse transcription-PCR for β-actin (97 bp) were performed.
All formalin-fixed paraffin-embedded (FFPE) and methacarn-fixed paraffin-embedded (MFPE) samples tested positive for GAPDH and β-actin by PCR. hGH was successfully detected in all MFPE samples, but in only 46.7% of the FFPE samples. Prolonged formalin fixation resulted in fewer GAPDH and β-actin PCR products, and amplification of hGH was not successful. The PCR and reverse transcription-PCR results were significantly affected by the duration of decalcification. The yield, purity, and integrity of mRNA progressively decreased with increased storage periods of paraffin blocks.
Fixation and storage should therefore be standardized in order to improve the quality of molecular pathologic diagnosis.
Nucleic acid preservation; Fixation procedures; Storage time
Human papillomavirus (HPV) is an oncogenic virus in cervical cancer and most invasive carcinomas (ICs) are caused by HPV16 and 18. However, the roles and contributions of other uncommon and rare genotypes remain uncertain.
HPV genotypes were retrospectively assessed using an HPV DNA chip that can specify up to 32 HPV genotypes. We arbitrarily regarded genotypes accounting for less than 6% of the total as uncommon and rare genotypes.
A total of 3,164 HPV-positive cases were enrolled. In groups 2A, 2B, 3, and unclassified HPV genotypes, 2.4% of cases with uncommon HPV genotypes (68, 26, 34, 53, 66, 69, 70, 73, 40, 42, 43, 44, 54, 55, 61, 62, 6, and 11) showed high grade squamous intraepithelial lesions and ICs. There were no HPV32- and 57-infected cases.
We found that the uncommon and rare HPV genotypes may provide incremental etiologic contributions in cervical carcinogenesis, especially HPV68, 70, and 53. Further studies on these uncommon and rare HPV genotypes will be of importance in establishing the significance of genotypes in different regions, especially in planning a strategy for further vaccine development as well as follow-up on the effectiveness of the currently used vaccines.
Human papillomavirus; Cervix uteri; Carcinogenesis; Genotype
A 24-year-old man was admitted due to an incidentally detected mass in his left testis, which showed radiopaque calcification on plain X-ray film. Left orchiectomy was performed, and the resected testis contained a well-demarcated, hard mass measuring 1.1 cm. Histological analysis revealed that the tumor was composed of neoplastic cells, fibrotic stroma, and laminated or irregularly shaped calcific bodies. The individual cells had abundant eosinophilic or clear cytoplasm with round nuclei, each of which contained one or two conspicuous nucleoli. They were arranged in cords, trabeculae, clusters, and diffuse sheets. There were several foci of intra-tubular growth patterns, with thickening of the basal lamina. Immunohistochemically, the neoplastic cells were positive for S-100 protein and vimentin, focally positive for inhibin alpha, and negative for cytokeratin, CD10, and Melan-A. In addition to reporting this rare case, we also review the relevant literature regarding large cell calcifying Sertoli cell tumors.
Testis; Sertoli cell tumor; Immunohistochemistry
Herein, we report a case of primary myxoid leiomyoma of the liver. A 60-year-old woman complained of upper abdominal fullness. Computed tomography showed a solid tumor (8 cm) in the liver. The patient underwent right hepatectomy and histological findings from the resected specimen revealed scattered bland spindle cells in a background of exuberant myxoid material. The tumor cells were immunoreactive for smooth muscle actin and desmin. No other lesions were found elsewhere in the body. Thus, the tumor was diagnosed as a primary myxoid leiomyoma of the liver.
Leiomyoma; Myxoma; Liver; Immunohistochemistry
Metastasis to the breast from colorectal carcinoma is rare, only a few cases have been reported in the literature, and no cases have been reported in a young, 28-year-old patient. This report confirms the occurrence of the disease in a younger age group. The patient was referred to the Breast Clinic with a history of a gradually increasing lump in her right breast for two weeks' duration. On clinical examination, a 2-cm firm lump was noted in the upper inner quadrant of the right breast, which was clinically benign; however, histological examination of the breast core biopsy together with immunohistochemistry confirmed metastatic colorectal adenocarcinoma. The primary colorectal carcinoma was later confirmed to be a stage pT4N2M1 tumor, and the Duke stage was C1. Histology with immunohistochemistry is very important in the diagnosis of cases of this nature, but the clinical correlation should be taken into consideration at multidisciplinary team meetings to decide the final management of the patient.
Colon; Breast; Immunohistochemistry; Metastasis
Carcinoma-associated fibroblasts (CAFs) contribute to carcinogenesis and cancer progression, although their origin and role remain unclear. We recently identified and investigated the in situ identity and implications of gastric submucosa-resident mesenchymal stem cells (GS-MSCs) in the progression of gastric carcinogenesis.
We isolated GS-MSCs from gastric submucosa using hydrogel-supported organ culture and defined their identity. Isolated cells were assessed in vitro by immunophenotype and mesengenic multipotency. Reciprocal interactions between GS-MSCs and gastric cancer cells were evaluated. To determine the role of GS-MSCs, xenografts were constructed of gastric cancer cells admixed with or without GS-MSCs.
Isolated cells fulfilled MSCs requirements in regard to plastic adherence, stromal cell immunophenotype, and multipotency. We demonstrated a paracrine loop that gastric cancer cells enhanced the migration, proliferation, and differentiation of GS-MSCs; additionally, GS-MSCs promoted the proliferation of gastric cancer cell in vitro. Xenograft experiments showed that GS-MSCs significantly promoted cancer growth and angiogenesis. GS-MSCs that integrated into gastric cancer became not only CAFs but also rarely endothelial cells which contributed to the formation of cellular and vascular cancer stroma.
Endogenous GS-MSCs play an important role in gastric cancer progression.
Gastric-resident mesenchymal stem cell; Carcinoma-associated fibroblast; Cancer stroma; Stomach neoplasms
Because there may be interdepartmental differences in macroscopic sampling of cholecystectomy specimens, we aimed to investigate differences between the longitudinal sampling technique and our classical sampling technique in cholecystectomy specimens in which there was no obvious malignancy.
Six hundred eight cholecystectomy specimens that were collected between 2011 and 2012 were included in this study. The first group included 273 specimens for which one sample was taken from each of the fundus, body, and neck regions (our classical technique). The second group included 335 specimens for which samples taken from the neck region and lengthwise from the fundus toward the neck were placed together in one cassette (longitudinal sampling). The Pearson chi-square, Fisher exact, and ANOVA tests were used and differences were considered significant at p<.05.
In the statistical analysis, although gallbladders in the first group were bigger, the average length of the samples taken in the second group was greater. Inflammatory cells, pyloric metaplasia, intestinal metaplasia, low grade dysplasia, and invasive carcinoma were seen more often in the second group.
In our study, the use of a longitudinal sampling technique enabled us to examine a longer mucosa and to detect more mucosal lesions than did our classical technique. Thus, longitudinal sampling can be an effective technique in detecting preinvasive lesions.
Cholecystectomy; Longitudinal sampling technique; Swiss-roll method; Preinvasive lesions; Incidental gallbladder cancer
Absolute lymphocyte count (ALC) in peripheral blood has recently been reported to be an independent prognostic factor in multiple myeloma (MM). Previous studies indicated that the absolute monocyte count (AMC) in peripheral blood reflects the state of the tumor microenvironment in lymphomas. Neither the utility of the AMC nor its relationship with ALC has been studied in MM.
The prognostic value of ALC, AMC, and the ALC/AMC ratio at the time of diagnosis was retrospectively examined in 189 patients with MM.
On univariate analysis, low ALC (<1,400 cells/µL), high AMC (≥490 cells/µL), and low ALC/AMC ratio (<2.9) were correlated with worse overall survival (OS) (p=.002, p=.038, and p=.001, respectively). On multivariate analysis, the ALC/AMC ratio was an independent prognostic factor (p=.047), whereas ALC and AMC were no longer statistical significant. Low ALC, high AMC, and low ALC/AMC ratio were associated with poor prognostic factors such as high International Staging System stage, plasmablastic morphology, hypoalbuminemia, and high β2-microglobulin.
Univariate analysis demonstrated that changes in ALC, AMC, and the ALC/AMC ratio are associated with patient survival in MM. Multivariate analysis showed that, of these factors, the ALC/AMC ratio was an independent prognostic factor for OS.
Multiple myeloma; Lymphocytes; Monocytes; Lymphocyte/monocyte ratio; Prognosis
The microtubule-associated protein Tau binds to both inner and outer surfaces of microtubules, leading to tubulin assembly and microtubule stabilization. The aim of this study was to evaluate the significance of Tau, α-tubulin, and βIII-tubulin expression in breast carcinoma and to assess their relationships with disease progression in the context of taxane treatment.
Immunohistochemical expressions of Tau, α-tubulin, and βIII-tubulin were assessed in 183 breast cancer cases. Expression was correlated with clinicopathologic parameters, disease progression and overall survival.
Tau expression was correlated with lymph node metastasis and estrogen receptor (ER) positivity (p=.003 and p<.001, respectively). Loss of α-tubulin was significantly correlated with distant metastasis (p=.034). Loss of βIII-tubulin was correlated with lymph node metastasis and ER positivity (p=.004 and p<.001, respectively). In taxane-treated cases, Tau expression and loss of α-tubulin and βIII-tubulin expression were related to disease progression (p=.001, p=.028, and p=.030, respectively). Tau expression was associated with a worse survival rate in taxane-treated patients (p=.049).
Tau expression and loss of α-tubulin and βIII-tubulin expression were correlated with aggressive behavior in taxane-treated breast cancer. Further evaluation of Tau, α-tubulin and βIII-tubulin may be useful in predicting clinical behavior and seeking therapeutic measures in taxane-based chemotherapy for breast cancer.
Tau proteins; Tubulin; Taxoids; Breast neoplasms
Glioblastomas may develop de novo (primary glioblastomas, P-GBLs) or through progression from lower-grade astrocytomas (secondary glioblastomas, S-GBLs). The aim of this study was to compare the immunohistochemical classification of glioblastomas with clinically determined P-GBLs and S-GBLs to identify the best combination of antibodies for immunohistochemical classification.
We evaluated the immunohistochemical expression of epidermal growth factor receptor (EGFR), p53, and isocitrate dehydrogenase 1 (IDH-1) in 150 glioblastoma cases.
According to clinical history, the glioblastomas analyzed in this study consisted of 146 P-GBLs and 4 S-GBLs. Immunohistochemical expression of EGFR, p53, and IDH-1 was observed in 62.6%, 49.3%, and 11.1%, respectively. Immunohistochemical profiles of EGFR(+)/p53(-), IDH-1(-)/EGFR(+)/p53(-), and EGFR(-)/p53(+) were noted in 41.3%, 40.2%, and 28.7%, respectively. Expression of IDH-1 and EGFR(-)/p53(+) was positively correlated with young age. The typical immunohistochemical features of S-GBLs comprised IDH-1(+)/EGFR(-)/p53(+), and were noted in 3.6% of clinically P-GBLs. The combination of IDH-1(-) or EGFR(+) was the best set of immunohistochemical stains for identifying P-GBLs, whereas the combination of IDH-1(+) and EGFR(-) was best for identifying S-GBLs.
We recommend a combination of IDH-1 and EGFR for immunohistochemical classification of glioblastomas. We expect our results to be useful for determining treatment strategies for glioblastoma patients.
Glioblastoma; Immunohistochemistry; IDH1 protein, human; Genes, erbB-1; Genes, p53
Primary squamous cell carcinoma (SCC) of the upper genital tract, including the endometrium, fallopian tubes, and ovaries, is extremely rare. It must be distinguished from the mucosal extension of primary cervical SCC because determination of the primary tumor site is important for tumor staging. However, patients with SCC of the fallopian tubes or ovarian surface have often undergone prior hysterectomy with inadequate examination of the cervix, making it difficult to determine the primary site.
We compared histologic findings, p16INK4a expression, and human papillomavirus (HPV) DNA status in four patients with primary SCC of the upper genital tract and five patients with primary cervical SCC extending to the mucosa of the upper genital tract.
All five SCCs of cervical origin showed strong expression of p16INK4a, whereas all four SCCs of the upper genital tract were negative, although one showed weak focal staining. Three of the five cervical SCCs were positive for HPV16 DNA, whereas all four primary SCCs of the upper genital tract were negative for HPV DNA.
Although a thorough histological examination is important, immunonegativity for p16INK4a and negative for HPV DNA may be useful adjuncts in determining primary SCCs of the upper genital tract.
Carcinoma, squamous cell; Genes, p16; DNA probes, HPV
Pre-existing non-neoplastic renal diseases or lesions may influence patient renal function after tumor removal. However, its description is often neglected or omitted in pathologic reports. To determine the incidence and clinical significance of non-neoplastic lesions, we retrospectively examined renal tissues obtained during 85 radical nephrectomies for renal cell carcinoma.
One paraffin-embedded tissue block from each case containing a sufficient amount of non-tumorous renal parenchyma was cut and processed with hematoxylin and eosin and periodic acid-Schiff methods. Non-neoplastic lesions of each histological compartment were semi-quantitatively and quantitatively evaluated.
Among the various histologic lesions found, tubular atrophy, arterial intimal thickening, and glomerulosclerosis were the most common (94.1%, 91.8%, and 88.2%, respectively). Glomerulosclerosis correlated with estimated glomerular filtration rate at the time of surgery, as well as at 1- and 5-years post-surgery (p=.0071), but tubulointerstitial fibrosis or arterial fibrous intimal thickening did not. Post-hoc analysis revealed that glomerulosclerosis of more than 20% predicted post-operative renal function. However, its significance disappeared when gender and age were considered.
In conclusion, non-neoplastic lesions, especially with regard to glomerulosclerosis percentage, should be described in pathology reports to provide additional information on renal function decline.
Nephrectomy; Carcinoma, renal cell; Glomerular filtration rate; Histology
Cerebrospinal fluid (CSF) examination can be used to verify the presence of primary malignancies as well as cases of central nervous system (CNS) metastasis. Because of its importance, there have been several studies concerning the sensitivity of CSF cytology. To determine the practical use and reproducibility of diagnoses based on CSF cytology, we evaluated this test by analyzing cytology results from consecutive CSF samples.
Between July 2010 and June 2013, 385 CSF cytology samples from 42 patients were collected. The samples were gathered using a ventricular catheter and reservoir. CSF cytology of all patients was examined more than two times with immunocytochemistry for cytokeratin.
Primary neoplastic sites and histologic types of patients' metastatic cancer were diverse. The overall sensitivity for detecting malignancy was 41.3%. Even within short-term intervals, diagnoses frequently changed.
Our results were inconsistent, with low sensitivity, when compared to the results of previous studies. However, CSF evaluation can still provide valuable diagnostic and prognostic information because adjuvant treatments are now routinely performed in patients with CNS metastasis. Negative CSF cytology results should not be ignored, and continuous CSF follow-up is essential for following the clinical course of patients with metastatic cancer involving the CNS.
Central nervous system; Neoplasm metastasis; Cerebrospinal fluid
Nevus sebaceus of Jadassohn is a congenital cutaneous hamartoma comprised of multiple skin structures. It has the potential to develop into variety of neoplasms of various epidermal adnexal origins. While multiple tumors may occasionally arise, it is unusual for more than four tumors to arise simultaneously within a single sebaceus nevus. Here in, we report a case of a 70-year-old woman with six neoplastic proliferations including a syringocystadenoma papilliferum, pigmented trichoblastoma, tubular apocrine adenoma, sebaceoma, tumors of follicular infundibulum and superficial epithelioma with sebaceus differentiation arising in a long standing nevus sebaceus on the scalp. Our case is extraordinary because a single nevus sebaceus contained six neoplastic proliferations with differentiation toward the folliculosebaceous-apocrine unit.
Syringocystadenoma papilliferum; Pigmented trichoblastoma; Tubular apocrine adenoma; Sebaceous differentiation; Nevus sebaceous of Jadassohn