Severe dysplasia can be distinguished from moderate and mild dysplasia of bronchial mucosa by changes in Ki-67 index.

Preneoplastic lesions on small bronchial biopsy specimens may cause a diagnostic dilemma. The aim of this study was to estimate karyometric variables and the Ki-67 index of preneoplastic bronchial lesions and squamous cell carcinoma of the lung. The study was performed on endoscopic samples of squamous cell carcinoma (n = 22), normal appearing mucosa surrounding carcinoma (n = 10), bronchial dysplasia of mild (n = 7), moderate (n = 6), and severe grade (n = 6), carcinoma in situ (n = 17), and normal mucosa from patients with chronic bronchitis (n = 26). Karyometric analysis was done using the image analyzer ImageJ 1.47q. Ki-67 activity was also quantified by ImageJ 1.47q with the plugin Cell Counter. The highest values of nuclear area were found in squamous cell carcinoma, and differences were statistically significant compared to normal mucosa, all grades of dysplasia and normal appearing mucosa surrounding carcinoma (p < 0.01). The Ki-67 index was significantly higher in squamous cell lung carcinoma compared to normal mucosa, mild and moderate dysplasia and normal appearing mucosa surrounding carcinoma (p < 0.01). The Ki-67 index was significantly higher in severe dysplasia than in mild and moderate dysplasia (p < 0.01). In conclusion, the Ki-67 index is a useful parameter for more objective grading and can be of prognostic value to determine the biological potential of preneoplastic bronchial lesions.

Markers of proliferation and cytokeratins in the differential diagnosis of jaw cysts.

We conducted a retrospective study to analyze the histologic and immunohistochemical findings in three main types of odontogenic cyst. We studied 90 archived cystic jaw lesions: 30 dentigerous cysts, 30 keratocystic odontogenic tumors, and 30 radicular cysts. The cyst types were identified on the basis of clinical, radiologic, and histopathologic findings. Immunohistochemical analyses included staining with Ki-67, p53, epidermal growth factor receptor (EGFR), cytokeratin (CK) 8, CK14, CK17, and CK18. Cell immunopositivity was evaluated for the entire epithelium. The criteria for Ki-67 and p53 positivity were dense and/or faint nuclear staining, and cells were considered EGFR-positive if they exhibited membrane staining and/or cytoplasm staining. For the cytokeratins, cells exhibiting cytoplasm staining were considered positive. Five representative fields of each lesion were selected and identified in each of the Ki-67- and p53-stained slides. We found a statistically significant difference in the ratio of Ki-67-positive cells in the entire layer between the keratocystic odontogenic tumors and both the dentigerous cysts and the radicular cysts. A statistically significant difference was observed in the ratio of p53-positive cells between the keratocystic odontogenic tumors and the radicular cysts. Cytokeratins proved to be useful in differentiating radicular cysts from other types of cystic jaw lesions because of their CK8-positive and CK17-negative immunolabeling.

Metastatic malignant melanoma of the uterus diagnosed by colposcopy.

Introduction: Primary and metastatic malignant melanomas represent a rare diagnosis with a small number of described cases. The aggressive nature of the tumor, non-specific symptoms, difficult diagnosis, and no official protocol about the treatment result in poor disease prognosis. Case Outline: The authors presented a 41-year-old multigravida patient. She had an operation of malignant melanoma in the occipital area of the head. She went to her gynecologist because of increased pale pink vaginal secretion. Gynecological examination didn't show any significant abnormalities apart from a slightly enlarged uterus. Papanicolaou test and vaginal secretion examination were normal. Colposcopically, a significant dark brown hyperpigmented area around 1 cm in size was observed on the posterior lip of the cervix, near the orifice and cervical canal, suspicious of melanoma, which was proven on targeted biopsy of the hyperpigmented change on the cervix, and by magnetic resonance imaging of the lesser pelvis. Classic hysterectomy with adnexectomy and regional pelvic lymphadenectomy were performed. Conclusion: This case report pointed out the significance of applying colposcopy in diagnosing suspected metastatic melanoma of the uterine cervix, along with other diagnostic methods and anamnestic data.

Asymptomatic flow of Rosai-Dorfman disease.

INTRODUCTION: Sinus histiocytosis with massive lymphadenopathy is a rare benign self-limiting disease of unknown etiology. The salivary gland involvement, indicating the extranodal character of the disease, often presents a diagnostic dilemma requiring immunohistochemical staining of surgically removed tumor to confirm the diagnosis. CASE REPORT: We report a 43-year-old man presented with an asymptomatic mass in the left mandibular angle. On physical examination, the lesion was described as a painless, mobile, firm-elastic consistency nodule, which measured 4 x 3 cm in diameter, with normal overlying skin. A mass with the same characteristics, dimensions 2 x 2 cm, was also noted in the right parotid region. No other changes in regional lymph nodes were detected. On macroscopic examination the lesion was firm, multilobulated, yellowish and rounded, while on microscopic examination the lesion was composed almost entirely of polygonal histiocytes with abundant cytoplasm, emperipolesis, plasma cells arranged in sheets, and lymphocytes scattered or within clusters. The observed histiocytes were found to be CD68 and S100 protein positive. CONCLUSION: Rosai-Dorfman disease is a beningn and frequently overlooked clinical and pathological entity that may be misinterpreted as a neoplastic disease.

Giant renal oncocytoma.

BACKGROUND: Renal onkocytoma is a distinctive benign tumor derived from epithelial cells of the distal renal tubules. These tumors are often clinically asymptomatic, diagnosed accidentally and difficult to distinguish from renal cell carcinoma. CASE REPORT: We presented a giant renal onkocytoma in a man aged 64, without any signs or symptoms of the urogenital system disorder. The preoperative diagnosis described the tumor mass of the right kidney, size 16 x 14 cm, and indicated a malignant tumor of kidney. The patient underwent radical nephrectomy. The tumor was encapsulated at the intersection with the characteristic central hyaline scar. Microscopically, it was built of uniform polygonal cells with abundant eosinophilic cytoplasm. Immunohystochemiclly, tumor cells were immunoreactive to CK AE1/AE3 and CD 117, but showed negative immunoreactivity to CK 7, RCC marker and Vimentin. CONCLUSION: Giant renal oncocytomas are rare tumors with benign clinical course. As a rule, they are discovered by accident. Clinical differentiation from malignant tumors of the kidney is not possible. They are treated surgically, mainly by radical nephrectomy. A definitive diagnosis is made only by histopathological examination of tumors using immunohistochemical marker panels.

A rare case of retroperitoneal malignant Triton tumor invading renal vein and small intestine.

INTRODUCTION: Malignant Triton tumor is a very rare malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation. Most of those tumors occur in patients with von Recklinghausen's disease or as a late complication of irradiation and commonly seen in the head, neck, extremities and trunk. CASE REPORT: We reported retroperitoneal malignant Triton tumor in a 57-year-old female patient. Skin lesions were not present, and there was no family history of neurofibromatosis or previous irradiation. The presented case is one of a few recorded in the specialized literature that occurs in the retroperitoneal space in sporadic form. In this case, tumor consisted of a multilobular mass was in close relation with the abdominal aorta and inferior vena cava and involved the renal vein with gross invasion of the small intestine. The patient underwent total resection of the tumor and left nefrectomy was performed. The small intestine 10 cm in length was also resected and end-to-end anastomosis was conducted. The postoperative course was uneventful and the patient was discharged from the hospital ten days after the surgery. CONCLUSION: Diagnostically, it is crucial to recognize this uncommon histological variant because malignant Triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does. The use of the immunohistochemistry is essential in making the correct diagnosis. Only appropriate pathological evaluation supported by immunostaining with S-100 protein and desmin confirmed the diagnosis. Aggressive surgical management treatment improves the prognosis of such cases with adjuvant radiotherapy.

Primary leptomeningeal melanocytosis--a case report with an autopsy diagnosis.

INTRODUCTION: Primary melanocytosis of the leptomeninges is a rare tumor, most likely originating from the melanocytes in the leptomeninges. The average survival is only about 5 months. CASE REPORT: A 61-years-old woman presented with headache, amaurosis and hallucinations lasted for two months, and she had been treated at the Clinic for Psychiatry and Clinic for Infectious Diseases. The cerebrospinal fluid analysis showed a lower level of glucose and a higher level of proteins. Small shaded areas of basal leptomeninges and hydrocephalus were found by computed tomography and magnetic resonance imaging. The autopsy showed a dark brown mass on basal leptomeninges with blurred boundaries. No pigmented skin lesions were found. Histopathological analysis revealed a primary leptomeningeal melanocytosis. CONCLUSION: Primary leptomeningeal melanocytosis is a rare tumor, difficult to diagnose. This case is being presented for its specificity, since this diagnosis is not frequently seen in practice.

Correlation of cell cycle regulatory proteins (p53 and p16(ink)4(a)) and bcl-2 oncoprotein with mitotic index and thickness of primary cutaneous malignant melanoma.

The purpose of the study was to determine the frequency of expression p53 and p16INK4a proteins and bcl-2 oncoprotein in malignant skin melanoma and to determine their correlation with the proliferative index and tumor thickness. The study involved 53 patients: 27 (51%) male and 26 (49%) female. Mitotic index showed a correlation with p53 protein expression, a negative correlation with p16INK4a protein expression. Statistically significant correlations were determined between the Breslow tumor thickness, Clark invasion level and p53 protein expression, as well as Breslow tumor thickness and bcl-2 oncoprotein expression (p<0.05), whereas there was no correlation between the p16INK4a protein expression and melanoma thicknes and Clark invasion level. Overexpression p53 protein and bcl-2 oncoprotein, with the loss p16INK4a protein of expression in the nodular melanoma, confirms a frequent loss of function of these tumor suppressor gene and oncogene, and indicates a vertical tumor growth phase. The loss of tumor suppression function the p53 protein and bcl-2 oncoprotein overexpression in cutaneous melanoma correlates with larger tumor thickness, whereas the overexpression of mutated p53 protein and loss p16INK4a protein of expression indicate a higher proliferative tumour potential. Therefore, these evaluated proteins may be the aggressive biological tumour activity markers.

[Histopathological characteristics and coexpression of p53 and p16(INK4a) proteins in renal cancer].

BACKGROUND/AIM: Renal carcinoma represents histologically heterogeneous group of malignant tumors, with various clinical aggressiveness. The frequency of p53 mutation in primal renal carcinoma is rare, although there are information about its heterogeneous accumulation. The loss of protein p16 expression in primal renal carcinoma is detected in 20-30% of the cases. The aim of this paper was to determine frequency of mutated protein p53 and expression of protein p16(INK4a) in renal carcinoma, to analyze their correlative relation and relation with the examined clinicopathological parameters. METHODS: The examination included 12 patients (66.7% men, 33.3% women), with patohistologically verified renal carcinoma. Expression of mutated form of protein p53 and protein p16 was determined in tissue samples, by immunohistochemical analysis using of mice monoclonical antibodies produced by DAKO, Denmark RESULTS: In 9 (75%) of the cases was detected mutated protein p53, of whom 66.6% had higher histological gradus of tumor (G3-4) and higher pathological stadium of the disease (pT3a-b) at the same time. In 7 (58.3%) and 5 (41.7%) of the cases expression of protein p16, the loss of expression of protein p16 were detected respectively. A statistically significant positive correlation was determined between pathological stadium of disease (TNM) and the degree of tumor differentiation (G) (p = 0.834; p < 0.001), as well as between TNM and mitotic index (p = 0.622; p = 0.031). CONCLUSION: A mutated form of protein p53 exists in 75% of the cases with the renal carcinoma and 66.6% of then have higher histological gradus of tumor and higher stadium of tumor disease at the same time. Coexpression of mutated protein p53 and protein p16(INK4a) in renal carcinoma is not statistically significant and it is not in correlation with clinicopathological parameters. Immunohistochemical analysis of mutated protein p53 in renal carcinoma can have predictive significance.

Giant paraovarian cyst in a child complicated with torsion.

BACKGROUND: A variety of benign cyst may occur in and around the ovary and broad ligament and may simulate serous cystadenomas. The majority of broad ligament and paraovarian epithelial tumors are serous neoplasms of low malignant potential and presented with a pelvic mass with or without ascites or pain, but without involvement of the ovary. Ovarian torsion and paraovarian serous cystadenoma are rarely reported. CASE REPORT: We presented a case of giant paraovarian cyst in an 14-year-old girl, with characteristics of serous cystadenomas grossly and microscopically, and complicated with double adnexal torsion. A computed tomography scan showed large hypodense cystic mass (measuring 30 x 26 x 12 cm), occupying the whole abdominal cavity, with no adhesion to the surrounding organs. CONCLUSION: Precise clinical data as well as pathological examinations based on immunohistochemical stainings were important in making the diagnosis. These rare cystic lesions of para/mesoovarian location in children and their unclear histogenesis might be a histopathological diagnostical problem.

[Inflammatory myofibroblastic tumor of the larynx].

BACKGROUND/AIM: Inflammatory myofibroblastic tumor (IMT) of the larynx is a rare borderline lesion composed of myofibroblastic and inflammatory cells. CASE REPORT: We presented a case of 77-year-old male with hoarseness for about three months. Laryngoscopy showed a polypoid tumor originated from the anterior commissure with glottic projection. Grossly, the tumor was 22 x 15 mm, whitish, oval nodus with firm consistency. Histologically, the lesion was composed of spindled to stellate cells arranged in a fascicular to storiform pattern and inflammatory cells: lymphocytes, histiocytes, plasma cells and neutrophils. The stroma was fibromyxoid and collagenous. Immunohistochemically, tumor cells showed strong positivity for actin and vimentin and negativity for cytokeratin, CD34, S100 and desmin. The proliferation (Ki67) was less than 10%. CONCLUSION: Inflammatory myofibroblastic tumor may be mistaken as a malignancy and the differential diagnosis can be difficult without immunohistochemistry. It is critical to recognize this uncommon entity to avoid unnecessary aggressive treatment.

Discriminant analysis of image karyometric variables in benign and malignant melanocytic skin lesions.

OBJECTIVE: To perform a quantitative analysis to identify which of 7 nuclear morphometry-related variables are of diagnostic value in distinguishing benign from malignant melanocytic skin lesions. STUDY DESIGN: At the Institute of Pathology, University of Nis, formalin-fixed, paraffin-embedded skin biopsies from 23 cases of benign nevi (18 intradermal and 5 junctional) and 25 cases of primary nodular malignant melanomas were retrieved. Specimens were routinely stained with hematoxylin and eosin and analyzed using a computer-assisted interactive image analysis system. Nuclear area, equivalent diameter, volume of equivalent sphere, perimeter, mean chord, circularity and integrated optical density were estimated after manual editing of binary images. RESULTS: In univariate analysis, 6 features were found to be significantly different between the benign and malignant groups (P < .0001); all measured nuclear variables (except circularity) were higher in malignant melanomas. No significant differences were found among lesions with respect to nuclear shape. Using discriminant function analysis, a correct diagnosis was achieved in 95.8% of benign nevi cases and 84.0% of malignant melanoma cases. The best discriminant variable was nuclear area. CONCLUSION: Image analysis is diagnostically relevant to the evaluation of melanocytic lesions of the skin. The area of the nucleus appeared to have potential for differentiating benign from malignant tumors and can be estimated in the course of routine histology.

Nuclear volume and total optical density in Down syndrome.

OBJECTIVE: To estimate nuclear size and integrated optical density of parenchymal cells from various organs in patients with Down syndrome and a control group. STUDY DESIGN: During the years 1988-2000, 14 cases of Down syndrome were found (8 male and 6 female). Ten infants without congenital anomalies died of respiratory distress syndrome and were used as a control group. Five nuclear variables were estimated: area, equivalent diameter, volume of equivalent sphere, roundness and total optical density (TOD). RESULTS: Mean nuclear volume and TOD of thyroid follicular cells were significantly lower in patients with Down syndrome (43.82 +/- 8.95 and 173.81 +/- 32.85 microns 3, respectively) than in the control group (65.46 +/- 15.31 and 234.58 +/- 32.85 microns 3, respectively) (P < .01). Mean hepatocite nuclear volume and TOD were significantly higher in the control group (165.54 +/- 55.42 and 220.84 +/- 51.75 microns 3, respectively) than in trisomy 21 (110.39 +/- 32.97 and 176.58 +/- 28.53 microns 3, respectively) (P < .05). CONCLUSION: The present results suggest altered gene expression in excessive genetic material, especially in thyroid follicular cells.

[Solid papillary breast carcinoma with mucinous differentiation]. / Solidni papilarni karcinom dojke sa mucinoznom diferencijacijom.

A case is reported of a solid variant of infiltrating papillary carcinoma of the breast with mucinous differentiation in a 74-year-old woman. Macroscopically, the tumor was solid and lobular, 4.5 cm in diameter. Light microscopy showed solid papillary invasive carcinoma mixed with infiltrating ductal carcinoma, not otherwise specified. Abundant intracellular and extracellular acid mucin produced by the solid papillary tumor cells was proven histochemically by: PAS, PAS-D, mucicarmine and alcian blue. Immunohistochemically, the papillary carcinoma cells were strongly reactive to estrogen receptors, and weakly to moderately reactive to smooth muscle actin. We suggest that papillary carcinoma of the breast could have potentially high degree of aggressiveness, and that differential diagnosis of these rare tumors might be a histopathological problem.