Clinicopathological significance of insulin-like growth factor-1 receptor expression in breast cancer.

OBJECTIVE: Insulin-like growth factor 1 receptor (IGF1R) is a receptor protein tyrosine kinase that is claimed to be related with tumor development and progression of breast cancer with some conflicting results in the literature. The aims of the study are to investigate expression of IGF1R, and correlate with clinicopathological parameters to clarify the significance of IGF1R on breast cancer. MATERIAL AND METHODS: IGF1R and Ki67 were applied immunohistochemically to the tissue microarray sections of 370 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings [ER, PR, HER2, CK5/6, and CK14] statistically. RESULTS: IGF1R overexpression showed direct correlation with Ki67 index (P=0.028), HER2 positivity (P=0.001), mitotic count (P=0.004), tumor grade (P=0.015), and geographic necrosis (P=0.023); and negative correlation with ER positivity (P=0.003). There was statistically significant difference between IGF1R expression and the molecular subtypes (P<0.001), mostly HER2+ phenotype. IGF1R expression was found to be higher in invasive ductal carcinoma (IDC) than invasive lobular carcinoma (ILC) (P=0.036). Both IGF1R and Ki67 expression were negatively correlated with disease-free survival (DFS) (P=0.020, P=0.023, respectively) and overall survival (OS) [P<0.001, each] rates. The inverse association between IGF1R overexpression and OS rate was also supported by multivariate analyses (P=0.025). CONCLUSIONS: Overexpression of IGF1R was found to be directly correlated with shorter DFS and OS as well as some clinicopathological features associated with adverse prognosis such as higher Ki67 index, mitotic count, tumor grade, presence of geographic necrosis, HER2 positivity, ER negativity, HER2+ molecular subtype, histological tumor type of IDC rather than ILC. Thus, IGF1R might be considered as an useful target for comprehensive future anti-tumor therapy investigations. Additionally, using IGF1R as well as Ki67 as a part of routine pathology practice might be fruitful in breast cancer therapy and prediction of prognosis. KEY WORDS: Breast carcinoma, IGF1R, Insulin-like growth factor-1 receptor, Immunohistochemistry, Prognosis.

Clinicopathological Significance of the Proliferation Markers Ki67, RacGAP1, and Topoisomerase 2 Alpha in Breast Cancer.

Objectives The aims of this study are to evaluate expressions of Ki67, RacGAP1 (MgcRacGAP) and topoisomerase 2 alpha (TOP2a), the markers related with cell proliferation that have been proposed to affect the prognosis in the literature and correlate the results with clinicopathological parameters of breast cancer patients. Methods Ki67, RacGAP1, and TOP2a antibodies were applied immunohistochemically to the tissue micrarray blocks of 457 female breast cancer patients. The results were correlated with clinical, prognostic, histopathological features, and other immunohistochemical findings (estrogen receptor [ER], progesterone receptor [PR], HER2, cytokeratin [CK]5/6, CK14, epidermal growth factor receptor [EGFR] and vimentin), statistically. Results Ki67 expression demonstrated direct correlation with TOP2a expression, mitotic count, tumor grade, geographic necrosis, basal-like phenotype. RacGAP1 expression was directly correlated with TOP2a expression, nipple invasion, and number of metastatic lymph nodes, and it was inversely correlated with PR expression. TOP2a expression was directly correlated with vimentin and Ki67 expressions, mitotic count, tumor grade, and geographic necrosis, and nipple invasion, and negatively correlated with ER and PR expressions. Higher TOP2a and Ki67 expressions were correlated with shorter overall survival. Higher TOP2a expression and RacGAP1 positivity were directly correlated with shorter disease-free survival. Conclusion This study showed that the overexpressions of Ki67, RacGAP1, and TOP2a affect the prognosis adversely, thus to develop target therapies against RacGAP1 and TOP2a as well as using Ki67 as a part of routine pathology practice might be beneficial in breast cancer therapy and prediction of prognosis.

Secondary Neoplasms in Children with Hodgkin's Lymphoma Receiving C-MOPP and Radiotherapy: Presentation of Four Cases.

Patients who survive Hodgkin lymphoma (HL) are at increased risk of secondary neoplasms (SNs). A wide variety of SNs have been reported, including leukemias, non-Hodgkin's lymphomas, and solid tumors, specifically breast and thyroid cancers. Herein we report subsequent neoplasms in four patients with HL receiving chemoradiotherapy. It is interesting that three SNs, fibrosarcoma, thyroid carcinoma, and retrobulbar meningioma, were observed in the radiation area in one of our patients. A hypopharyngeal epithelioid malignant peripheral nerve sheath tumor as an unusual secondary malignant neoplasm developed in another patient, while a benign thyroid nodule and invasive ductal breast carcinoma were observed at different times in the female patient. Follicular adenoma of the thyroid gland developed in one of our patients.

A rare case of primary inoculation tuberculosis seen after varicella.

Primary inoculation tuberculosis (TB) is a rare form of cutaneous TB resulting from direct introduction of Mycobacterium tuberculosis into the skin or mucosa of a previously uninfected, nonimmune person. We herein report the first case, to our knowledge, of primary inoculation TB to be seen after varicella; this case explains the possible mechanism of varicella-zoster virus-mediated transient cellular immune suppression that predisposed the patient to cutaneous TB. In this case, we believe that varicella-zoster virus (VZV) infection predisposed the patient to primary inoculation TB by leading to direct inoculation of tuberculosis bacilli through vesicles or by suppressing cellular immunity.

Pathologic basis of pyogenic, nonpyogenic, and other spondylitis and discitis.

Pyogenic spondylitis and discitis are usually seen following a recent infection or surgery. A septic embolus causes an infarcted area within the bone. Pyogenic spondylitis is characterized by edema, vascular leakage, and supportive inflammatory reaction characterized with polymorphonuclear leukocytes. In tuberculosis of the spine, active lesions are characterized by formation of epithelioid granulomas with central caseating necrosis. Mycobacterium tuberculosis can be shown by histochemical stains for acid-fast bacteria or by immunochemistry. In brucella spondylitis, microgranulomatous proliferation composed of histiocytes containing numerous bacilli without caseating necrosis is characteristic. Brucella melitensis can be shown on histochemical Gram stain.

A proven case of cutaneous rhizopus infection presenting with severe limb pain very soon after induction treatment in a patient with acute lymphoblastic leukemia.

Objective and Importance. Invasive mucormycosis may complicate the course of patients with hematologic malignancies and has a very high mortality rate. Early diagnosis and aggressive approach combined with surgical and medical treatment have paramount importance for cure. Clinical Presentation. We report here a case of a patient with acute lymphoblastic leukemia presenting with a subcutaneous mass lesion which was sampled by an ultrasound guided needle biopsy. The pathology showed microorganisms with aseptate hyphae with wide, irregular walls and more or less branching with highly vertical angles which suggested a mold infection. The specimen was also cultured where Rhizopus spp. grew. Conclusion. Posaconazole 200 mg QID was commenced. She recovered from neutropenia and pain on day 20 of treatment. After 4 courses of hyper-CVAD chemotherapy, the remaining soft tissue mass was removed surgically and she underwent allogeneic HSCT from a full matched sibling donor under secondary prophylaxis.

Primary Intracerebral Alveolar Soft Part Sarcoma in an 11-Year-Old Girl: Case Report and Review of the Literature.

Alveolar soft part sarcoma (ASPS), a rarely observed tumor, is a soft tissue sarcoma with an unidentified cell origin. It constitutes 0.5-1.0% of all soft tissue sarcomas. It may appear in various parts of the body, but mostly observed in the trunk and the extremities. It has a high metastasis potential. To the best of our knowledge, only three cases of primary intracranial ASPS without a demonstrable lesion elsewhere is encountered. An 11-year-old girl was operated because of fronto-parietal mass lesion by craniotomy. Pathological examination revealed ASPS and no primary focus was detected. In spite of radiotherapy and chemotherapy as an adjuvant therapy, after 45 months she had a second operation for recurrence of the tumor. Since it is possible to observe metastases in late phases, up to 30 years, the patients must be followed up for a long period. Although radiotherapy and chemotherapy followed by surgery is the most accepted treatment strategy, the prognosis is still poor.

Mediastinal neurothekeoma: a rare tumor.

Neurothekeoma, also known as nerve sheath myxoma, is a benign nerve sheath tumor that usually arises in the cutaneous nerves of the head, neck, or upper extremities. Extracutaneous placement is very rare. Mediastinal neurothekeoma has not previously been reported in the English literature. A 30-year-old woman was admitted to our clinic with back pain. A smooth-edged mass found in her paravertebral region, and a neurogenic tumor was suspected. The tumor was completely excised. Final pathology revealed it to be a mediastinal neurothekeoma.

Osteochondroma of the nasal dorsum presenting as a nasal hump.

We describe the case of a 24-year-old man who underwent open septorhinoplasty for the treatment of progressive nasal disfigurement caused by a nasal hump. Postoperative histopathology of the resected hump revealed that it was an osteochondroma. The patient showed no evidence of recurrence during 2 years of follow-up. To the best of our knowledge, this is the first case of an osteochondroma involving the nasal dorsum to be reported in the English-language literature.

Solid tumors in Turkish children: a multicenter study.

BACKGROUND: This paper presents a detailed incidence study on childhood solid tumors comprising a histopathology-based documentation of benign and malignant lesions. METHODS: The Ankara Pediatric Pathology Working Group collected databases of pediatric solid tumors from six pediatric reference centers in order to analyze the incidence, distribution and some epidemiologic characteristics of the tumors and to establish a multicenter database for further studies. A five-year retrospective archive search was carried out. Excluding epithelial tumors of the skin, leukemia, lymphoreticular system neoplasias, metastatic tumors, and hamartomas, 1362 solid tumors in 1358 patients were classified according to age, sex, localization, histopathology and clinical behavior. RESULTS: The male/female ratio was 0.9; 14.8% (201) of the patients belonged to 0-1 year age group, 20.7% (281) to 2-4 years, 25.9% (352) to 5-10 years, 22.2% (301) to 11-14 years, and 16.4% (223) to 15-18 years. Among all tumors, 708 (52.0%) were malignant, 645 (47.4%) benign tumors, 2 (0.1%) borderline tumors, and 2 (0.1%) unknown behavioral tumors. Malignant tumors were found in 50.2% (357) of female patients and in 54.0% (349) of male patients. A balanced distribution between benign and malignant entities among children under 18 years was observed. Comparison between the age groups revealed malignant cases outnumbered benign cases under 4 years of age while benign tumor numbers increased after 10 years of age. The most common entities in the malignant group were of sympathetic nervous system origin, while soft tissue tumors far outnumbered the others in the benign group. CONCLUSIONS: We conclude that the cancer patterns of children in the Ankara region mostly resemble with those of the western population. This study provides useful information on the diagnosis of solid tumors in children and highlights variations in cancer incidence in different age groups.

A comprehensive morphological study for basal-like breast carcinomas with comparison to nonbasal-like carcinomas.

BACKGROUND: Breast carcinomas can be classified into five subtypes based on gene expression profiling or immunohistochemical characteristics. Among these subtypes, basal-like breast carcinomas (BLBCs) are one of the most studied group, due to their poor prognosis. The aim of this study was to investigate the prevalance, morphological and immunohistochemical features of BLBCs, in Turkish population. METHODS: Five hundred invasive breast carcinomas were reviewed for several morphological features and immunostained for oestrogen and progesterone receptors, c-ERB-B2, cytokeratin5/6, cytokeratin14, vimentin and epidermal growth factor receptor (EGFR). Basal-like breast carcinoma was defined as a triple negative tumor with cytokeratin5/6 and/or EGFR positive. RESULTS: The prevalance of BLBC was 9.6%. All medullary carcinomas and 55.6% of metaplastic carcinomas showed basal-like immunophenotype. Patients with BLBC were younger (p=0.04) and had higher-grade tumors (p<0.0001). Morphologic features associated with BLBC included increased mitosis, nuclear pleomorphism, presence of geographic and/or central necrosis, pushing margin of invasion and stromal lymphocytic response (p<0.0001). Presence of prominent nucleoli and vesicular nuclear chromatin were the cytological features correlated with basal-like phenotype (p<0.0001). On multivariate analyses, BLBCs were associated with high mitotic number (p<0.0001), the presence of vesicular chromatin (p=0.004), high tubular grade (p=0.011), lymphocytic response (p=0.031) and the absence of carcinoma insitu (p=0.039). Vimentin was positive in 53.2% of BLBCs, while cytokeratin14 was less frequently expressed (27.7%). CONCLUSIONS: BLBCs have some distinctive, but not pathognomonical, morphological features. Paying attention to these features and adding cytokeratin14 and vimentin to the immunohistochemical panel can help the definitive diagnosis of BLBCs. VIRTUAL SLIDE: Http://www.diagnosticpathology.diagnomx.eu/vs/5962175467857400.

Metaplastic breast carcinomas and their relationship with basal-like phenotype.

OBJECTIVE: Metaplastic carcinoma is a rare tumor showing high histological grade and low hormone receptor expression. It has pure epithelial and mixed types. Studies have suggested that metaplastic carcinomas may have a basal-like profile. Our aim was to evaluate the clinicopathological features of 11 metaplastic carcinomas and determine their resemblance to basal-like breast carcinomas regarding their morphological and immunohistochemical profile. MATERIAL AND METHOD: Eleven metaplastic carcinoma cases were reviewed for their histopathological features. All tumors but one were evaluated for the immunohistochemical expressions of the cytokeratin 5/6, cytokeratin 14 and epidermal growth factor receptor; and hormonal status was assessed. RESULTS: Four of eleven cases were carcinoma with chondroid metaplasia, 3 were adenosquamous carcinoma, 2 were squamous cell carcinoma and 2 were carcinosarcoma. The mean patient age was 53 years and the mean tumor size was 5,1 cm. Histological grade was 3 for all with a nuclear grade of 3. Average mitotic count was 31/10 high power fields. Four cases had a central scar, 5 had central necrosis and 7 had geographic necrosis. Tumor growth pattern was pushing in 6 cases and no carcinoma in-situ was identified in 5 cases. Seven of 10 patients had axillary lymph node metastasis. Seven of 10 cases were triple-negative (estrogen receptor-, progesterone receptor-, HER2-) and 6 of them were positive for cytokeratin 5/6 and/or epidermal growth factor receptor, consistent with basal-like immunophenotype. Cytokeratin 14 was positive in 7 cases. CONCLUSION: Metaplastic carcinomas are large-sized, high-grade tumors with prominent nuclear pleomorphism and frequent mitosis. They rarely overexpress hormone receptors and HER2 and generally have basal-like immunophenotype.

A previously unreported malignancy of the thyroid.

Ameloblastic fibrosarcoma or ameloblastic sarcoma is an extremely rare odontogenic neoplasm. We report a case of an ameloblastic fibrosarcoma arising from thyroid gland in a 44 year-old woman. Following total thyroidectomy, a histopathologic, immunohistologic, and genotypic examination revealed ameloblastic fibrosarcoma. The tumor was composed of odontogenic epithelium, resembling that of ameloblastoma, and a mesenchymal part exhibiting features of fibrosarcoma. To our review, our case represents the first report of ameloblastic fibrosarcoma of the thyroid gland. Ameloblastic fibrosarcoma may arise from thyroid gland.

The evaluation of CD99 immunoreactivity and EWS/FLI1 translocation by fluorescence in situ hybridization in central PNETs and Ewing's sarcoma family of tumors.

Ewing's sarcoma family of tumors (ESFTs) are indicated by malignant, small, round and blue cell tumors of the bone and soft tissue. Gene rearrangements between EWS gene on chromosome 22q12 and members of the ETS gene family are common in and specific to ESFTs. Another defining characteristic of ESFTs is their membranous expression of the CD99. In contrast, such translocations and immunoreactivity are not found in central primitive neuroectodermal tumors (cPNETs). The aim of this study was to investigate the detection of EWS/FLI1 translocations and CD99 immunoreactivity in order to evaluate their clinicopathological features and their roles in the differential diagnosis of these tumors. In this study, we investigated CD99 immunoreactivity using immunohistochemistry and Ewing's sarcoma / Friend leukaemia virus integration 1 (EWS/FLI1) translocation using the fluorescence in situ hybridization (FISH) method in 23 cases. CD99 expression was detected in 10/11 (90%) ESFT cases and 2/7 cPNET cases. In 18 cases EWS/FLI1 translocation was examined using the FISH method. The EWS/FLI1 translocations were detected in 7/8 (87.5%) ESFTs cases, whereas non of 8 cPNET cases were detected with this translocation. One case could not be classified as either central or peripheral, showed EWS/FLI1 translocation. There was a statistically significant difference in CD99 expression (p = 0.0013) and EWS/FLI1 translocation (p = 0,002) between cPNETs and ESFTs cases. In conclusion, CD99 expression and EWS/FLI1 translocation are specific and sensitive markers in the diagnosis of ESFTs. However, these were often not found in cases of cPNET. Therefore, in the diagnosis of ESFTs, clinical, radiological, histopathological and immunohistochemical parameters should always be evaluated together.

Parathyroid adenoma and chondrosarcoma after treatment of pediatric Hodgkin disease.

Treatment of Hodgkin disease (HD) with chemoradiotherapy in children is associated with increased risk for developing secondary neoplasms. Parathyroid adenoma (PTA) and chondrosarcoma (CS) are quite rare types of secondary neoplasms after HD. We describe a 5-year-old boy with stage IV HD, successfully treated with MOPP (mechlorethamine, vincristine, procarbazine, and prednisone)/ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 35 Gy mantle radiotherapy who developed primary hyperparathyroidism because of benign PTA at the age of 20 years, and died of CS in thoracic vertebrae at the age of 22 years. Consecutive occurrence of PTA and CS after treatment of pediatric HD, to the best of our knowledge, has not been reported earlier.

The histopathologic evaluation of soft tissue changes in rabbit extremity after different dose-fractionation schemes of interstitial high dose rate (HDR) brachytherapy.

BACKGROUND: The use of HDR in the treatment of soft tissue sarcoma had been on the rise. However, there was limited study to evaluate the effect of different fractionation schemes on soft tissue and the optimal HDR scheme. AIMS: We aimed to assess the histopathologic changes on soft tissue after different HDR brachytherapy doses. METHODS: The subjects were divided into three groups. Each group included 10 limbs. Group A had only an applicator without radiation, group B received a total of 24 Gy at 6 Gy per fraction, twice a day, and group C received a total of 13.5 Gy in a single fraction. The histopathologic findings were grouped into soft tissue pathology-1 (edema, inflammation, endothelial proliferation, necrosis) and soft tissue pathology-2 (atrophy, calcification, vascular hyalinization, fibrosis) (STP-1-2). RESULTS: The highest mean grade values of STP-1 and STP-2 were observed in group C (0.95 and 1.45) in comparison to group A (0.45 and 0.85) and group B (0.65 and 0.9). The difference in STP-1 was found significant only between groups A and C and the difference in STP-2 was found both between groups A and C and groups B and C. CONCLUSION: In our experimental study it was shown that the fractionated interstitial HDR had both lower rate and severity of toxicity in comparison to a single high dose fraction. Before using a single fractionated regimen in the clinic, the increased morbidity related to the irreversible early toxicities or progressive late toxicities should be kept in mind.

Giant neurothekeoma in the forearm of an infant.

Neurothekeomas are benign tumours of nerve sheath origin. Neurothekeomas present most commonly on the head and neck and upper extremities. These are usually small, slow growing tumours. Most patients with neurothekeoma are young women. We describe a 1-year-old infant with a large and extensive neurothekeoma in the upper extremity. We believe that our patient is one of the youngest cases and the tumour is probably the largest and most extensive neurothekeoma reported in the literature.

Histiocytic sarcoma: PET-CT evaluation of a rare entity.

Histiocytic sarcoma is a rare malignancy of hematopoietic origin. Lymph nodes, skin, and extranodal sites, especially gastrointestinal tract, are commonly involved. Some cases reported in the past as non-Hodgkin's lymphoma are now classified as histiocytic sarcoma by detailed immunohistochemical studies. Patients with clinically localized disease have a good prognosis whereas those with lymphatic involvement have an aggressive course. In our case, histiocytic sarcoma was detected, originating from the skin over the left shoulder associated with disseminated lymphadenopathy. A positron emission tomography/computed tomography examination was done for evaluating the extent of the disease which showed pathologic increased 18F-fluorodeoxyglucose uptake in the lymph nodes, indicating widespread disease. The pertinent literature is reviewed.

Angiographically occult vascular malformation of the third ventricle.

Angiographically occult vascular malformations (AOVM) are cerebrovascular malformations that are not demonstrable on cerebral angiography. The majority of AOVMs located in the third ventricle are cavernous malformations. To the best of our knowledge an angiographically occult arteriovenous malformation (AOAVM) of the third ventricle has not been previously reported. We report an unusual vascular malformation of the third ventricle presenting with hydrocephalus due to mass effect, verified histopathologically as an AOAVM.