Turkish Journal of Pathology - 2017; 33(3)

Diagnostic and Treatment Reproducibility of Cervical Intraepithelial Neoplasia / Squamous Intraepithelial Lesion and Factors Affecting the Diagnosis

2017-09-01

Objective: Inter-observer differences in the diagnosis of HPV related cervical lesions are problematic and response of gynecologists to these diagnostic entities is non-standardized. This study evaluated the diagnostic reproducibility of “cervical intraepithelial neoplasia” (CIN) and “squamous intraepithelial lesion” (SIL) diagnoses. Material and Method: 19 pathologists evaluated 66 cases once using H&E slides and once with immunohistochemical studies (p16, Ki-67 and Pro-ExC). Management response to diagnoses was evaluated amongst 12 gynecologists. Pathologists and gynecologists were also given a questionnaire about how additional information like smear results and age modify diagnosis and management. Results: We show moderate interobserver diagnostic reproducibility amongst pathologists. The overall kappa value was 0.50 and 0.59 using the CIN and SIL classifications respectively. Impact of immunohistochemical evaluation on interpretation of cases differed and there was lack of statistically significant improvement of interobserver diagnostic reproducibility with the addition of immunohistochemistry. We saw that choice of treatment methods amongst gynecologists varied and overall concordance was only fair to moderate. The CIN2 diagnostic category was seen to have the lowest percentage agreement amongst both pathologists and gynecologists. We showed that pathologists had diagnostic “styles” and gynecologists had management “styles”. Conclusion: In summary each pathologist had different diagnostic tendencies which were affected not only by histopathology and marker studies, but also by the patient management tendencies of the gynecologist that the pathologist worked with. The two-tiered modified Bethesda system improved diagnostic agreement. We concluded that immunohistochemistry should be used only to resolve problems in select cases and not for every case.

Programmed Death Ligand 1 (PD-L1) Expression in Malignant Mesenchymal Tumors

2017-09-01

Objective: Programmed death ligand 1 (PD-L1) found on tumor cells has recently been reported to have a key role in the development and dissemination of many tumors, such as lung and breast carcinomas. In this study, we retrospectively analyzed PD-L1 expression among different types of sarcomas. Material and Method: Tissue microarrays of 3-4 mm diameter were composed from paraffin blocks of 222 various sarcomas. Slides prepared from microarrays were stained for PD-L1 antibody (Cell Signaling, E1L3N�) using Leica Bond Autostainer. Any membranous staining over 5% of the cells was regarded as positive. Quantitative real-time PCR with TaqMan gene expression assays for PDL1 was performed using whole sections from FFPE tissue of PD-L1 positive cases, by normalizing absolute values to β-actin. Relative expression level of mRNA of PDL1 was calculated and scored using Log102(threshold cycle of b-actin - threshold cycle of PDL1). Results: Immunohistochemically, PD-L1 expression was present in 34 of 222 (15%) sarcomas. 5/13 (39%) undifferentiated pleomorphic sarcomas, 6/18 (33%) malignant peripheral nerve sheath tumors, 5/16 (31%) dedifferentiated liposarcomas, 4/19 (21%) rhabdomyosarcomas, 2/16 (13%) epithelioid sarcomas, 2/15 (13%) leiomyosarcomas, 3/26 (12%) synovial sarcomas, 1/18 (6%) myxoid liposarcoma, 1/2 (50%) extraskeletal myxoid chondrosarcoma, 1/3 (33%) alveolar soft part sarcoma, 1/3 (33%) parachordoma/myoepithelioma, 1/5 (20%) pleomorphic liposarcoma, 1/7 (14%) angiosarcoma, 1/8 (13%) Ewing sarcoma showed PD-L1 expression. Cases of solitary fibrous tumor/hemangiopericytoma (18), desmoplastic round cell tumor (14), Ewing-like sarcoma (6), epithelioid hemangioendothelioma (5), clear cell sarcoma (4), myxofibrosarcoma (4), low grade fibromyxoid sarcoma (2) were all negative. Tumor-infiltrating hematopoietic cells were positive for PD-L1 in 32 cases (15%) with only 2 cases overlapping with PD-L1 staining in tumoral cells. Sixteen of 34 (47%) immunohistochemically PD-L1 positive cases showed significant but low-level PD-L1 mRNA overexpression. Conclusion: We have shown PD-L1 expression in a subset of sarcomas, both at the protein and mRNA level. High-grade pleomorphic sarcomas tend to show more frequent PD-L1 expression. Clinical trials are necessary to further assess the effect of anti PD-L1 drugs on sarcomas showing PD-L1 expression.

Prognostic Value of Twist-1, E-cadherin and EZH2 in Prostate Cancer: An Immunohistochemical Study

Aziza E. ABDELRAHMAN, Shimaa A. ARAFA, Ragab A. AHMED — 2017-09-01

Objective: There is an urgent need to identify molecular biomarkers rather than clinical markers to distinguish aggressive prostate cancer from the indolent majority for proper treatment and accurate prediction of prognosis. We aimed to investigate the immunohistochemical expression of epithelial-mesenchymal transition (EMT)-related molecules (Twist-1 and E-cadherin) and the stem cell marker EZH2 in prostate cancer and to assess their ability to identify the high-risk patients, in a trial to explore their prognostic implications. Material and Method: Immunohistochemical expression of Twist-1, E-cadherin and EZH2 in 50 specimens of prostate cancer and 20 cases of benign prostatic hyperplasia were studied. The relationship between their expression and the clinicopathological variables, biochemical recurrence, and biochemical progression-free survival were investigated. Results: Our results revealed that high Twist-1, as well as high EZH2 expression, was strongly associated with higher pre-treatment PSA level, Gleason score ≥7, advanced tumor stage, lymph node involvement, distant metastasis and biochemical progression. Aberrant E-cadherin expression was significantly associated with higher pre-treatment PSA level, Gleason score ≥7, advanced tumor stage, lymph node involvement, and distant metastasis. A significant positive correlation between Twist-1 and EZH2 expression was found (p<0.001), while E-cadherin expression showed a negative correlation with both markers (p<0.001). A significant association was found between high Twist-1, high EZH2& aberrant E-cadherin expression, and shorter biochemical progression-free survival. Conclusion: The high Twist-1 expression, aberrant E-cadherin and high EZH2 expression in primary prostate cancer are considered as adverse prognostic markers of an aggressive tumor with high metastatic potential. Assessment of their expression level would contribute to the accurate prediction of biochemical progression.

Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1), CD8+ Tumor-Infiltrating Lymphocytes and p53 in Non-Small Cell Lung Cancer: An Immunohistochemical Study

2017-09-01

Objective: Programmed cell death ligand-1 interacts with the immune receptors on the surface of CD8+ tumor infiltrating lymphocytes and PD-1, thereby blocking its anti-tumor activity. Therapeutics suppression of this interaction will show a promise in the treatment of non-small cell lung cancer by restoring the functional anti-tumor T-cell activity. We aimed to evaluate the association between the immunohistochemical expression of PD-L1, stromal CD8+ tumor infiltrating lymphocytes and p53 with the clinicopathological characteristics, response to chemotherapy, progression-free-survival, and overall survival. Material and Method: We examined the immunohistochemical expression of PD-L1, stromal CD8+ TILs, and p53 expression in 50 patients with advanced stage (III&IV) non-small cell lung cancer. Results: PD-L1 was expressed in 56% of the studied cases. PD-L1 expression was related to unfavorable response to the therapy without significant difference. PD-L1 expression was significantly associated with disease progression, poor progression-free-survival & overall survival. CD8+ TILs were high in 32% of the cases. Tumors with high CD8+ TILs showed a partial response to therapy and had a better progression-free-survival and overall survival. p53 expressed in 82% of the studied cases. There was a significant negative association between PD-L1 and CD8+ TILs (p=0.009), while a non-significant association was found between p53 and PD-L1 (p=0.183). Conclusion: PD-L1 overexpression is an unfavorable prognostic marker, while the high CD8 + TILs is a good prognostic marker in non-small cell lung cancer. PD-L1 immunohistochemical assessment may be used for the selection of patients legible for treatment with anti-PD-L1 therapy.

The Role of CD34 and D2-40 in the Differentiation of Dermatofibroma and Dermatofibrosarcoma Protuberans

2017-09-01

Objective: Dermatofibroma (DF) is a benign fibrohistiocytic tumor whereas dermatofibrosarcoma protuberans (DFSP) has intermediate malignant potential. CD34 is the most commonly used antibody in differentiating these tumors. Various studies have stated the rates of D2-40 expression as 0-50% in DFSPs and 86-100% in DFs. Our aim in this study was to determine the expression of CD34 and D2-40 in DFs and DFSPs and the possible use of D2-40 in the differential diagnosis of these lesions. Material and Method: This is a retrospective study including 30 DF and 15 DFSP cases which were reevaluated for epidermal changes, the presence of a transmission zone (Grenz zone), infiltration of soft tissues, infiltration pattern and histologic subtypes in addition to cellular pleomorphism, nuclear atypia, and necrosis. A manual immunohistochemistry procedure was performed with D2-40 and CD 34 antibodies using a representative paraffin block. Results: The average age was 37.36 and 42.86 years in the DF and DFSP cases. The average diameter was 0.9 and 5.03 cm, respectively, for the DFs and DFSPs. There was a significant correlation between the two entities for sex, localization and diameter of the lesion. A significant difference was found between the positivity of CD34 and D2-40 in DFs and DFSPs. Conclusion: Additional immunohistochemical markers may be needed in DFs with CD34 positivity. Our results showed the additional helpful role of this marker in problematic cases.

Correlation of COX- 2 Expression in Colorectal Carcinoma with Clinicopathological Features

Sandhya VENKATACHALA, Manjula RAJENDRAN — 2017-09-01

Objective: Colorectal carcinoma is the most common neoplasm of the gastrointestinal tract. COX-2 expression is upregulated in colorectal carcinoma. Therefore its assessment would identify patients amenable to adjuvant anticyclooxygenase therapy. We studied COX-2 immunoexpression in colorectal adenocarcinoma and correlated it with clinicopathological features as age, gender, tumor location, tumor size, degree of differentiation, and TNM stage. Material and Method: Sixty-five consecutive cases of colorectal adenocarcinoma were retrieved from the records of the Pathology Department of a tertiary care hospital. The tumors were categorized as low positive and high positive based on their total COX-2 scores, which is the sum of proportion and intensity scores of immunostaining, and were correlated with clinicopathological features. Statistical analysis was done using the Chi-square test and Kendall's Tau–b correlation method. Results: COX-2 was expressed in 86.2% of cases including 90% of left colonic carcinomas and 77.3% of right colonic carcinomas. Lymph node metastasis was present in 22.2%, 25% and 47.75% of COX-2 negative, low positive and high positive tumors respectively. High positive COX-2 cases constituted 33.3% of stage I, 58.8% of stage II, 80% of stage III and 100% of stage IV tumors. About 56.6% of well differentiated, 66.6% of moderately differentiated and 100% of poorly differentiated carcinomas showed high COX-2 expression. The COX-2 overexpression was associated with advancing depth of invasion (p=0.021), stage of tumor (p=0.05), more frequent lymph node metastasis and decreasing degree of differentiation. Conclusion: The association of COX-2 overexpression with increasing stage and depth of invasion may justify the use of COX-2 inhibitors as an adjuvant to chemo and radiotherapy.

Can Cutting-Needle Biopsy Be an Alternative to Excisional Biopsy in Lymph Node Pathologies?

2017-09-01

Objective: We aimed to compare cutting-needle biopsy (CNB) diagnoses with excisional biopsy diagnoses of enlarging lymph nodes and to determine the diagnostic value of CNB. Material and Method: Out of the 291 cases that underwent CNB from lymph nodes between 2010 and 2016, 60 were included in the study in which pathological lymph nodes were excised after CNB. Demographic information, pathology and imaging reports, the diameters of the lymph nodes and the length of the CNBs of these cases were obtained from the hospital registry system. Diagnoses of the CNBs and excisional biopsies were then compared. Results: According to the excisional biopsy diagnosis, 7 of the 60 cases (11.7%) were benign and 53 of them (88.3%) were malignant. 28 (53%) of the malignant cases were diagnosed as Hodgkin’s lymphoma while the others (47%) got a non-Hodgkin’s lymphoma diagnosis. In the 8 non-diagnostic CNBs, 3(37%) of them were found to be benign/reactive, while 5 (63%) were diagnosed as malign lymphoma in excisional biopsy. Similarly, 7(64%) of the 11 cases diagnosed as benign/reactive in CNB, were found to be malignant with excisional biopsy. When CNB and excisional biopsy were compared, sensitivity and specificity were 90% and 100%; positive predictive value (PPV) and negative predictive value (NPV) were 100% and 0%, respectively, and the diagnostic accuracy rate (DV) was 86.5%. The mean diameter of the benign lymph nodes was 26.1 mm and the mean diameter of the malignant ones was 35.6 mm. There was no significant difference between malignant and benign lymph node size (p>0.05). There was also no statistically significant difference between CNB length and correct diagnosis (p=0.233). Conclusion: CNB is a non-invasive procedure. It is an alternative to excisional biopsy because of its low morbidity and low cost. However, the sensitivity of CNB is lower than its specificity, and we recommend the surgical excision of lymph nodes with a clinically strong neoplasm suspicion because of the presence of false negatives in 7 cases.

Adenomyoepithelial Adenosis of Breast: A Rare Case Report

Bhaskar MITRA , Mallika PAL, Tarak Nath SAHA, Ashok MAITI — 2017-09-01

Myoepithelial cells of the breast and their hyperplasia is found in many benign conditions resulting in a spectrum of lesions of myoepitheliosis to myoepithelial carcinoma. We present a rare case of adenomyoepithelial adenosis in a 17-year-old female who presented with a palpable right breast lump. Although considered benign, adenomyoepithelial lesions have a high chance of recurrence due to inadequate excision. Recurrence and even metastasis are therefore important issues in the follow-up of adenomyoepithelial lesions.

Subcutaneous Leiomyosarcoma Metastasized to the Lymph Nodes Involved with Small Lymphocytic Lymphoma / Chronic Lymphocytic Leukemia

Ayfer KAMALI POLAT, Atilla SORAN, Amal KANBOUR-SHAKIR, Howard EDINGTON — 2017-09-01

Herein, we present a case of a 76-year-old Caucasian man with a very large fungating, ulcerating mass, involving the right neck and parotid area, which developed while he was being treated for chronic lymphocytic leukemia/small lymphocytic lymphoma. Resection of the fungating right neck tumor, right modified radical neck dissection, and right superficial parotidectomy with flap reconstruction were performed. The final pathological diagnosis was high-grade leiomyosarcoma of the skin and the subcutaneous tissue, with invasion into the skeletal muscle, skin, and soft tissue. Additionally, the sarcoma had metastasized to the lymph nodes that were involved diffusely by lymphoma. The most interesting fact for this case is coincidence of three rare occurrences which were soft tissue sarcomas of subcutaneous leiomyosarcoma form and its metastasis to same lymph nodes that were involved with lymphoma.

A Translocation Renal Cell Carcinoma with Skeletal Muscle Metastasis in a Child

2017-09-01

Renal cell carcinoma is a tumor that is well known for a high rate of metastasis to several locations like the lung, liver and bones. Skeletal muscle is a rare location for dissemination of the disease. Herein, we describe a 7-year-old boy who presented with flank pain. On physical examination, an abdominal mass located on the left kidney as well as a solid palpable lesion on the left upper arm were detected. Total nephrectomy with subsequent excision of the arm mass was performed. Pathology examination revealed presence of translocation renal cell carcinoma. The patient received α-interferon followed by multikinase inhibitor (Sorafenib) treatment but was lost due to progressive disease. This is the first description of a pediatric patient with skeletal muscle metastases of translocation renal cell carcinoma in the literature.

Angiocentric Glioma: The Infiltrative Glioma with Ependymal Differentiation

2017-09-01

Angiocentric glioma is an epileptogenic, infiltrative, low grade glial tumor, with ependymal and astrocytic differentiation, most commonly seen in young adults and the pediatric age group. Herein we report a case of 21-year-old male patient who presented with fever and pharmaco-resistant seizures. Computed tomography revealed an iso-dense mass lesion in the gyrus rectus of the left frontal lobe. On magnetic resonance imaging the mass was hyperintense on both T1- and T2-weighted images with no contrast enhancement. Histopathological examination revealed monomorphous tumor cells diffusely infiltrating the neuropil with circumferential, radial, or longitudinal angiocentric alignment and subpial aggregation with perpendicular alignment of the cells to the pial surface. Among central nervous system tumors with ependymal differentiation, this distinct entity is the one with an infiltrating growth pattern. In spite of the infiltrating pattern, it does not seem to have a potential for aggressive behavior.

Mandibular Actinomyces Infection Mimicking a Malignancy: Case Report

2017-09-01

Actinomycosis is a rare, chronic, suppurative and granulomatous disease caused by Actinomyces israelii, which is a filamentous, anaerobic, gram-positive, saprophytic organism in the oral cavity. Diagnosis of actinomycosis depends on positive culture or identification of Actinomyces colonies and sulfur granules in histological specimens. In our case, a mass had been growing in the mandible for eight months. The mass appeared to be malignant, both clinically and radiologically. A histopathological examination of the mandible revealed actinomycosis. It should be noted that actinomycosis can mimic a malignancy, and for differential diagnosis, bone biopsy or fine-needle aspiration should be performed pre-operatively.

Congenital Complete Tracheal Ring in a Neonate: A Case Report

2017-09-01

Abnormalities of the upper airway tract lead to congenital high airway obstruction and may complicate neonatal airway management in the delivery room. Congenital complete tracheal rings are a rare and unusual tracheal anomaly, usually presenting in the neonate or infant as respiratory distress. The clinical presentation can vary from almost asymptomatic patients to near-fatal airway obstruction. It may exist as an isolated entity, or in association with other congenital malformations, in particular, cardiac anomalies along with vascular rings and pulmonary slings. Other associated anomalies have also been reported, for example, chromosomal anomalies, malformation of other parts of the respiratory tract, esophagus and skeletal systems. Here, we report an extreme case of VACTERL/TACRD association presented with congenital complete tracheal ring, encephalocele, bilateral radial agenesis with absent thumbs, equinovalgus deformity on right foot, low-set ears and micrognathia.

Benign Malformative Lesion of the Skull: Hamartoma with Ectopic Elements or Choristoma?

Ece MERAM, Hakan KARABA�LI, Christine GLASTONBURY, Tarik T�HAN, P�nar KARABA�LI — 2017-09-01

Hamartoma and choristoma are terms that describe non-neoplastic, mass-forming malformative lesions. Although each lesion has a different composition, they have been used interchangeably in many reports, especially for malformative lesions containing ectopic or heterologous elements. We report a three month-old girl who was brought to the clinic with a mass lesion at the posterior fontanel, composed of predominantly osteo-cartilaginous tissue admixed with skeletal muscle, peripheral nerve tissue, and ganglion. The mass was resected completely. The composition of this benign lesion with ectopic elements was consistent with an osteo-cartilaginous hamartoma. We discuss the biological and clinical aspects such malformative lesions within the skull to highlight the inconsistencies of the nomenclature used in the literature.