A systematic review on performance characteristics of FNA of renal lesions: It is time for a standardized classification system.

BACKGROUND: The incidence of renal tumors has steadily increased over the past decade. In this study, the authors performed a systematic review and analysis of the literature on renal fine-needle aspiration (FNA) to determine its performance and explore whether a standardized classification system can be used for reporting renal FNA cytology. METHODS: A systematic search of published articles on renal FNA was conducted. The data on FNA and histologic diagnosis were extracted and categorized, and the risk of malignancy was calculated. Different scenarios were used to estimate FNA performance statistics. RESULTS: Of the 3766 potentially relevant studies, 23 met the inclusion criteria of the study. The 2231 FNA cases included were re-categorized according to the classification system, rendering 142 (6.36%) nondiagnostic, 270 (12.1%) nonneoplastic, 271 (12.14%) benign neoplasm, 65 (2.91%) renal neoplasm with unknown malignant potential, oncocytic type, 25 (1.12%) atypia of undetermined significance, 60 (2.68%) suspicious for malignancy, and 1398 (62.66%) malignant FNA diagnoses. The risk of malignancy in these cases was 65.4%, 18.1%, 16.6%, 16.9%, 60%, 73.3%, and 96.9%, respectively. According to the classification system, the study indicated that the accuracy of renal FNA was between 91% and 95%, the sensitivity was 90.9%-96.7%, and the specificity was 82%-92% in different scenarios. CONCLUSIONS: There is a need for a standardized reporting in renal cytology that will improve the sensitivity and accuracy of renal cytology, reduce the rate of indeterminate diagnoses, and alter the management strategies of renal lesions. Based on the available literature, a new reporting system is proposed, including categories with an associated risk of malignancy.

A Low-Risk HPV-Associated Well-Differentiated Squamous Cell Carcinoma of the Cervix with Low-Grade Squamous Intraepithelial Lesion Morphology: Clinical and Pathologic Diagnostic Difficulties and Review of the Literature.

Approximately 95% of cervical squamous cell carcinomas are associated with high-risk HPV, with a small number of HPV-independent tumors. However, low-risk HPV types have also been detected in rare cervical squamous cell carcinomas. Low-grade squamous intraepithelial lesion-related changes are a rare morphologic finding in cervical squamous cell carcinoma. We present the case of a 30-yr-old woman who presented with pelvic pain and foul-smelling vaginal discharge showing an exophytic lesion protruding from the cervix. Repeated superficial biopsies showed a low-grade squamous intraepithelial lesion (LSIL) characterized by binucleation and koilocytosis. Chromogenic in-situ hybridization revealed the presence of HPV6/11. The absence of high-risk HPV was confirmed by PCR. After following the patient for nine months without intervention, type III hysterectomy and bilateral pelvic paraaortic lymphadenectomy were performed. Microscopic examination showed well-differentiated squamous cell carcinoma with solid epithelial islands and extensive eosinophilic cytoplasm without pleomorphism. HPV 6 and 11 were also detected with chromogenic in-situ hybridization. Neoplasm invaded the full-thickness of the cervical wall and infiltrated the vagina, parametrium, the proximal ureter and bladder. The patient who received chemoradiotherapy is disease-free at 36 months follow-up. Low-risk HPV-related well-differentiated invasive squamous lesions exist, and such lesions could be a diagnostic pitfall for gynecologists and pathologists; in these cases, radiologic-pathologic correlation and radiologic guided biopsy are mandatory.

Characterization of the Subcellular Distribution of Phospho-ß-catenin in Colorectal Cancer.

BACKGROUND/AIM: ß-Catenin is a multifunctional protein, which is localized to different subcellular compartments of the normal colon epithelium. The hyperactivation of Wnt pathway results in the nuclear accumulation of ß-catenin and induction of colorectal carcinogenesis. Although N-terminally hypo-phosphorylated ß-catenin (active ß-catenin) is known as the transcriptionally active form, phospho-S33/S37/T41-ß-catenin (phospho-ß-catenin) can also accumulate in the nucleus. In this study, we aimed to characterize the subcellular distribution of phospho-ß-catenin and the other forms of ß-catenin in normal colon epithelium and colorectal cancer (CRC). MATERIALS AND METHODS: Phosphorylated, hypo-phosphorylated, and the total pool of ß-catenin were evaluated in colon epithelium and CRC using immunohistochemistry, immunofluorescence staining, and western blotting. Tissue microarrays were used to determine the expression pattern of phospho-ß-catenin in CRC samples. RESULTS: Almost 11% (49/452) of CRCs expressed moderate to high levels of phospho-ß-catenin in the nucleus. In addition, hypo-phosphorylated and phosphorylated forms of ß-catenin localized to different subcellular regions in normal colon epithelium and CRC. Immunoblotting experiments suggested that truncated phospho-ß-catenin forms can be found in CRCs. CONCLUSION: Phospho-ß-catenin accumulates in the nucleus and different molecular weight ß-catenin proteins are present in colon cancer cells. To elaborate on the functional significance of nuclear phospho-ß-catenin, further studies should be performed.

Non-choriocarcinomatous trophoblastic tumors of testis in postchemotherapy retroperitoneal lymph node dissections.

Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, pathologists' familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000-2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (n = 5), placental site trophoblastic tumor (n = 2), epithelioid trophoblastic tumor (ETT) (n = 4), and coinciding PSTT + ETT (n = 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated ß-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal ß-HCG levels. All patients had follow-ups ranging from 8 to 118 months (mean 42.3 months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated ß-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.

Endobronchial Primary Pulmonary Angiomatoid Fibrous Histiocytoma in a Patient with Testicular Germ Cell Tumor: An Evidence Against Somatic Transformation.

Primary Pulmonary Angiomatoid Fibrous Histiocytoma is a recently described soft tissue tumor with challenging differential diagnosis both clinically and pathologically due to its rarity in this location. It may also occur as a secondary malignancy and its occurrence either as a somatic malignancy arising in the germ cell tumor or as a secondary malignancy after chemotherapy is questionable. In this report, we present a 29-year-old male patient with a mass in the lower lobe of the left lung, who underwent orchiectomy and received adjuvant chemotherapy due to a mixed germ cell tumor 8 years ago. Morphology, immunophenotype, and molecular findings were consistent with the diagnosis of primary pulmonary angiomatoid fibrous histiocytoma. Fluorescent in situ hybridization was unable to demonstrate the presence of 12p amplification or isochromosome 12p, which is known as the key event in the development of testicular germ cell neoplasia even present in somatic malignancies arising in germ cell tumors. Our results support that angiomatoid fibrous histiocytoma arising as a secondary malignancy does not represent the somatic transformation of germ cell tumors.

STK4 deficiency and EBV-associated lymphoproliferative disorders, emphasis on histomorphology, and review of literature.

Aberrations of the STK4 gene in humans result in an autosomal recessively inherited primary immunodeficiency. We identified three patients with STK4 deficiency who had presented to our hospital and reviewed their biopsy samples with the goal of detailing the characteristics of STK4 deficiency from a pathology perspective. Case 1 was a 20-year-old male who presented with cervical and supraclavicular lymphadenopathy which showed plasmacytic hyperplasia and a concurrent bronchial mass, with AA amyloidosis and EBV-associated "polymorphic lymphoproliferative disorder (LPD) resembling polymorphic post-transplant LPD." The second case was an 8-year-old girl with abdominal lymphadenopathy; biopsy revealed a complex lymphoproliferation which consisted of EBV-associated "polymorphic LPD resembling polymorphic post-transplant LPD," plasmacytic hyperplasia, granulomatous reaction, and a CD4- and PD-1-positive clonal T cell proliferation. The third was a 15-year-old girl with a laryngeal mass, representing a high-grade B cell lymphoma with prominent plasmacytic differentiation. Our cases emphasize the complex and challenging histopathology of lymphoid proliferations in patients with STK4 deficiency.

Long-standing aggressive angiomyxoma as a paratesticular mass: A case report and review of literature.

OBJECTIVES: Aggressive angiomyxoma is known as a mesenchymal tumor of premenopausal women and it is extremely rare in men. METHODS: Herein, we report a 66-year-old male with a firm scrotal mass that had gradually enlarged over 20 years. RESULTS: Radiological studies revealed 10 x 15 cm mass lesion confined to right scrotum with neither local invasion nor distant metastasis. Inguinal orchiectomy was performed and histopathology showed characteristic features of an aggressive angiomyxoma occupying paratesticular region, which was a challenging diagnosis due to its unexpected occurrence in the male gender. CONCLUSION: Aggressive angiomyxoma is mostly considered as a benign tumor in females despite its propensity for local recurrence. Whether it may show a divergent biological behavior in men is unknown as the reported cases are too few.