Turkish Journal of Pathology - 2014; 30(3)

CAMTA1 Immunostaining is not Useful in Differentiating Epithelioid Hemangioendothelioma from its Potential Mimickers

Zarifa YUS�FL�, Kemal K�SEMEHMETO�LU — 2014-09-01

Objective: Epithelioid hemangioendothelioma is a rare member of vascular tumors of intermediate malignancy. Recently, presence of t(1;3) translocation and WWTR1/CAMTA1 gene fusion, which enhances CAMTA1 expression, are found to be specific to this tumor. We investigated the CAMTA1 immune expression profile of epithelioid hemangioendothelioma and its potential mimickers using a commercially available CAMTA1 antibody. Material and Method: Standard whole sections from the formalin fixed, paraffin embedded blocks of 12 epithelioid hemangioendotheliomas, 10 angiosarcomas, 9 epithelioid sarcomas, 8 malignant melanomas, 8 signet ring carcinomas, 7 lobular carcinomas of breast, 2 epithelioid mesotheliomas, 2 rhabdoid tumors and 12 miscellaneous hemangiomas were immunostained for anti-CAMTA1 (ab64119, 1:200; Abcam) after pretreatment with citrate pH 6.0 for 20 minutes using Leica Bond detection kit with DAB chromogen. Strong nuclear CAMTA1 expression was scored for its extent as ‘negative’ (<5% positive), ‘+1’ (5-25% positive), ‘2+’ (25-50% positive) and ‘3+’ (>50% positive). Results: In 60 out of 70 cases (86%) either 2+ or 3+ strong nuclear staining was seen. Eighty-three % of epithelioid hemangioendotheliomas, 100% of angiosarcomas, 89% of epithelioid sarcomas, 89% of malignant melanomas, 63% of signet ring carcinomas, 71% of lobular carcinomas of breast, 100% of epithelioid mesotheliomas, 50% of rhabdoid tumors and 100% of hemangiomas were stained. Besides neurons, CAMTA1 expression was also observed in squamous epithelium, skin adnexa, breast lobules, prostate glands, bile ducts, colonic mucosa and gastric pits. Conclusion: Epithelioid hemangioendothelioma, its potential morphological mimickers and other benign or malignant vascular tumors showed strong and diffuse CAMTA1 expression, nullifying the potential use of CAMTA1 immunohistochemistry as an adjunct in the differential diagnosis.

Detection of HPV Positivity by Immunohistochemistry in Colposcopic Cervical Biopsies with a Cytological Diagnosis of ASCUS

G�ldeniz AKSAN DESTEL�, Ebru DEM�RALAY, T�rkan G�RSU, Ali AYHAN — 2014-09-01

Objective: Many epidemiological studies have shown that human papillomavirus related infections play a major role in cervical preinvasive and invasive lesions. ASCUS (atypical cells of undetermined significance) observed in about 4-5% of all cervical cytology specimens. We searched for the presence of HPV with immunohistochemical methods in the biopsy material of patients diagnosed with ASCUS using cytology. Material and Method: The colposcopic biopsy or Loop Electro Excisional Procedure (LEEP) material of 115 patients with a diagnosis of ASCUS were evaluated. HPV (type 6,11,16,18,31,33,42,51,52,56 and 58) immunohistochemistry was applied to all materials. The relationship between the biopsy results and HPV positivity was investigated. Results: Cervical intraepithelial neoplasia (CIN) I was found in 34.8%, CIN II in 13% and CIN III in 9.6% of the patients and cervicitis was present in 42.6% of the patients. HPV immunohistochemistry was positive in 11 cases (9.6%) and no staining was seen in 104 cases (90.4%). No positive staining was seen in the chronic cervicitis cases. The rate of positive staining was 15% (6/34) in the CIN I diagnosed group, 20% (3/12) in the CIN II diagnosed group and 18.2% (2/9) in the CIN III diagnosed group. Conclusion: HPV positivity was found to be lower compared to the literature both in total and in cases diagnosed by biopsy. No staining occurred in any patient with cervicitis. In conclusion, we believe that immunohistochemical examination is not an appropriate method for the determination of HPV.

A Histopathologic Analysis of 50 Eyes Primarily Enucleated for Retinoblastoma in a Tertiary Cancer Center in Jordan

2014-09-01

Objective: To analyze the histopathologic features of the eyes with intraocular retinoblastoma primarily treated by enucleation in a tertiary cancer center in Jordan. Material and Method: A retrospective case series of 50 eyes for 49 patients who had pathologically confirmed retinoblastoma after enucleation as primary therapy. The main outcome measures included demographics, laterality, international classification of intraocular retinoblastoma, choroid invasion, optic nerve invasion, anterior chamber invasion, and tumor differentiation. Results: The median age at enucleation was 30 months. Twenty-seven (55%) patients were males, and 19 (39%) patients had bilateral retinoblastoma. High risk pathological features were seen as massive choroid invasion in 9 (18%) eyes, post-laminar optic nerve invasion in 7 (14%) eyes, and anterior chamber, iris or ciliary body invasion in 7 (14%) eyes. Thirty-seven (74%) tumors were well/moderately differentiated, and 13 (26%) were poorly differentiated. Poorly differentiated tumors presented later (median 31 months) than well/ moderately differentiated tumors (26 months) and were associated with a higher incidence of high-risk pathological features. No single ICRB group C eye had high-risk pathological features, while 17% and 4% of group D eyes and 28% and 33% of group E eyes had massive choroid invasion and post-laminar optic nerve invasion, respectively. Eighteen (36%) patients received adjuvant chemotherapy for high risk pathological features, and at median follow up of 40 months, no single case had metastasis or was dead. Conclusion: Our pathologic findings were similar to the developed world. They were supportive of the predictive power of the international classification of retinoblastoma staging system for the likelihood of high risk pathological features. Poorly differentiated tumors were associated with a higher incidence of high risk pathological features than well/moderately differentiated tumors.

The Expression of STAT3, BCL-XL and MMP-2 Proteins in Colon Adenocarcinomas and their Relationship with Prognostic Factors

G�khan ARTA�, H. �brahim �ZERCAN — 2014-09-01

Objective: Colon adenocarcinomas are the most common malignancy of the gastrointestinal tract. Many factors are described in the prognosis. Herein we aimed to determine the relationship between signal transducer and activator of transcription 3(STAT3), B-cell lymphoma-extra large (Bcl-xL) and matrix metalloproteinase-2 (MMP-2) expression in colon adenocarcinomas and their relationship with prognostic factors. Material and Method: A total of 45 colon adenocarcinomas (15 well, 15 moderately, 15 poorly differentiated) and 15 normal colon mucosa samples were selected randomly. The STAT3, Bcl-xL and MMP-2 immunohistochemicals were applied to the samples. Results: There was a significant difference between the normal mucosa and carcinoma group regarding the STAT3 staining diffuseness and intensity (p<0.05), but not for Bcl-xL (p>0.05). The intensity of MMP-2 significantly differed between the normal mucosa and the carcinoma group (p<0.05). The diffuseness of STAT3 and the intensity of MMP2 showed a significant association with the degree of differentiation (p<0.05). The intensity and diffuseness of BcL-xL did not show a relationship with the degree of differentiation (p>0.05). Evaluation of the diffuseness and intensity of the three markers with lymph node metastasis and tumor size revealed that only MMP2 diffuseness had a negative correlation with tumor size (r= -0.318). Conclusion: We observed that Bcl-xL does not have a role in the diagnosis of colon adenocarcinomas or the detection of the degree of differentiation, a prognostic factor, but such a relationship was observed for STAT3 and MMP-2.

Intraoperative Frozen Section in Ovarian Neoplasms; A Tertiary Center Experience

2014-09-01

Objective: Frozen section is an accurate diagnostic tool with some unavoidable pitfalls in gynecologic tumors. We aimed to evaluate the diagnostic value of frozen section, and to detect the factors causing erroneous diagnosis in ovarian tumors. Material and Method: Frozen section and paraffin section reports of 282 patients with ovarian neoplasms diagnosed between July 2006 and January 2013 in our institute were re-analyzed. Results were grouped into benign, borderline (for epithelial tumors) and malignant categories and compared between frozen section and paraffin section diagnosis, statistically. Results: Overall diagnostic accuracy of frozen section was 96.5%. Sensitivity of frozen section for benign, borderline and malignant tumors were 97.5%, 95.8%, and 95.6% and the related specificities were 97.5%, 97.6%, and 100%, respectively. We found the lowest positive predictive value in borderline group (79.3%), all of them with mucinous type epithelium. Second frequent discordant tumor type was immature teratoma. Conclusion: Apart from the limitations of frozen section, pathologists should be aware of the pitfalls of technique and tumor types and tend to sample from the solid areas particularly in mucinous tumors and teratomas to avoid inappropriate surgery.

Perinatal Autopsy Evaluation of 2150 Autopsies in the �ukurova Region of Turkey

2014-09-01

Objective: We aimed to document the reasons of perinatal deaths in a large autopsy series performed in our institute, which is a reference center in the �ukurova region of Turkey. Material and Method: The study included 2150 autopsies performed between January 2000 and December 2012at our institute. Diagnoses were categorized according to the detected pathologies; congenital malformations were detailed based on systems. Results: A pathology was detected in 1619 of 2150 (73.3%) autopsies. Congenital malformations were the most common diagnosis with 68.2%. Neural tube defects and central nervous system malformations were the most frequent system malformation in 28.8% of cases, followed by the urogenital system (11.4%) and musculoskeletal system (8.3%), respectively. Malformation syndromes including multisystem anomalies were defined in 109 cases (9.3%). Conclusion: Congenital malformations are the most common reason for perinatal deaths, with autopsy having an additive role to prenatal and genetic evaluations and providing foresight for planning a subsequent pregnancy.

Chondrocutaneous Branchial Remnants or Cartilaginous Choristoma: Terminology, Biological Behavior and Salience of Bilateral Cervical Lesions

Bal CHANDER, Sunder Singh DOGRA, Rashmi RAINA, Chanderdeep SHARMA, Renu SHARMA — 2014-09-01

Objective: To present and critically examine the spectrum of chondrocutaneous branchial remnants or accessory pinna, including rare case of bilateral cervical lesions, and to explain the basis of the biological behavior. Material and Method: Five cases of pediatric chondrocutaneous branchial remnants or accessory pinna were included. The ratios of the longest dimensions of the external ear to that of the accessory tragus/chondrocutaneous branchial remnants were calculated. Results: The size and rate of growth of chondrocutaneous branchial remnants or accessory pinna were found to be inversely proportional to the distance between the lesions and the normal pinna. Conclusion: The current literature and norms of terminology dictate that two different terminologies for lesions that are essentially histologically identical should be avoided. Chondrocutaneous branchial remnants, accessory pinna/tragus and chondroid/ cartilaginous choristomas are identical lesions with similar pathogeneses and should be referred to as choristomas.

TTF-1 may not be a Reliable Marker for Differentiating Metastasis from Brain Tumors

Bet�l �NAL, �enay YILDIRIM, Cem SEZER, Din� S�REN — 2014-09-01

Objective: TTF-1 is widely used as an immunohistochemical marker of lung and thyroid tumors. However, TTF-1 expression has been described in tumors from other sites. The presence of TTF-1 expression in primary brain tumors is largely unclear and has not been clearly specified yet. We characterized expression of two TTF-1 clones in primary brain tumors with relevance to tumor types and grades. Material and Method: We studied immunohistochemistry with tissue micro-array, using both clones (8G7G3/1 and SPT24) in 45 primary brain tumors of different types and grades. Our cases consisted of 1 grade I, 7 grade II, 4 grade III, 20 grade IV astrocytic tumors; 9 meningiomas, 2 oligodendrogliomas, 1 schwannoma and 1 medulloblastoma. Results: We have found TTF-1 nuclear staining using the SPT24 clone in 4 cases (3 cases were grade IV and 1 was grade III). Focal and weak staining was seen in three cases and moderate-strong and diffuse staining was seen in one case. All the tumors were negative with clone 8G7G3/1. Clone SPT24 was more sensitive but less specific. Conclusion: TTF-1 can also be expressed in primary brain tumors, particularly grade III to IV tumors. TTF-1 expression was a rare finding in previous studies, however strong and diffuse staining was not observed until today. We think that TTF-1 nuclear expression in high-grade astrocytic tumors cannot rule out primaries even when diffuse and strong staining. Clinical and pathological parameters should be evaluated together.

Plexiform Pulmonary Arteriopathy in a 2 Year-Old Boy

2014-09-01

Idiopathic pulmonary arterial hypertension is a rare disease in children. We report a case of a 2-year old boy admitted to the intensive care unit of our hospital for severe dyspnea and epistaxis. Laboratory investigations showed hemolytic anemia with schizocytes and severe thrombocytopenia. Cardiac investigations diagnosed supra-systemic pulmonary arterial hypertension, which was refractory to maximal medical treatment. On evolution, he had several cardiac arrests and finally died 8 days after admission. Autopsy was performed and showed typical lesions of idiopathic pulmonary hypertensive arteriopathy characterized by plexiform lesions of the interlobular arteries containing numerous disseminated intravascular microthrombi. The rest of the family was screened, DNA was stored, and genetic study of BMPR2 was planned.

Co-Existence of a Large Ovarian Hemangioma and Microscopic Dysgerminoma in a 10-Year Old Child

Mehmet KEFEL�, Filiz KARAG�Z, Anais MALPICA — 2014-09-01

Ovarian hemangioma is an uncommon ovarian tumor occurring in patients in different age groups. It is usually seen as small, asymptomatic mass, which is detected incidentally. On rare occasions, this type of tumor can be associated with other gynecological neoplasms. In this report, we present the clinicopathologic features of a case of ovarian hemangioma coexisting with multiple microscopic foci of dysgerminoma in a 10-year-old child. The patient presented with acute abdomen. Magnetic resonance imaging revealed a left ovarian mass and subsequent left salpingo-oophorectomy was performed. Grossly, the mass was 9.5 cm in diameter and contained hemorrhage and necrosis. Microscopic examination showed that the tumor was mostly composed of hemangioma. Additionally, there were three microscopic foci of dysgerminoma between the hemangioma and ovarian cortex. Immunohistochemical studies showed that dysgerminoma foci were positive for PLAP, Oct4 and CD117. To our knowledge, this is the first case of the above-described association ever reported.

Myopericytoma of the Liver Hilus: A Case Report

2014-09-01

Pericytic tumours is a new category recently introduced in soft tissue pathology describing those entities sharing evidence of myoid differentiation and a tendency of spindle or more rounded cells to grow in a perivascular fashion. The great majority of pericytic tumours are benign but recurrence has been described as well as very rare malignant cases with an aggressive behaviour. Although pericytic tumours arise most commonly in the subcutaneous tissue of distal extremities in middle age patients, additional cases have been recently described in many other organs. Here we describe a case of a 57-year-old man with an 8.5 cm mass of the liver hilus diagnosed as myopericytoma, with particular reference to its biological potential and differential diagnosis. It is important for the pathologists to take this diagnosis into consideration as well for a better management of patient care.

Congenital Mature Cystic Teratoma of the Lateral Neck Presenting as Cystic Hygroma: A Rare Case Report with Literature Review

2014-09-01

Teratoma of the neck is a rare extra-gonadal teratoma. Although it can be seen in adult, most of the cases present in fetal life or early childhood. Grading and classification of teratoma is important for management and prognosis. Decision making between mature and immature teratoma is sometime challenging if it is not composed of extensive unusual neuroectodermal tissue component. We reported a rare case of huge congenital mature cystic teratoma composted of various neuroectodermal tissues in an 8-month-old boy; it was located at the lateral neck and mimicked congenital cystic hygroma. A literature review was done to grade and classify the tumour.

Primary Chondroblastic Osteosarcoma of the Breast

2014-09-01

Pure sarcomas of the breast are uncommon, accounting for less than 1% of primary breast malignant tumors. Mammary osteogenic sarcomas are very rare and less than 100 cases have been reported in literature. They mainly affect older and middle aged women and are highly aggressive. We report an additional case in a 56-year-old woman. Histological and immunohistological characteristics were similar to those described in other localizations. Differential diagnosis involves phyllodes sarcoma, breast metaplastic carcinoma with chondroid and osteoid differentiation, osteosarcoma of the ribs, and metastatic osteosarcoma. The prognosis is poor.

Solid Pseudopapillary Neoplasm of the Pancreas: Report of a Rare Case and Review of the Literature

Arzu Ne�e YENER, Manuk MANUKYAN, Ahmet M�D�, Rahmi �UBUK — 2014-09-01

Solid pseudopapillary neoplasm, a rare primary neoplasm of the pancreas that typically affects young women, is a relatively indolent entity with favorable prognosis. We here report a 20-year-old young girl with solid pseudopapillary neoplasm who presented with mild dull abdominal discomfort without any significant laboratory findings. On MRI, a heterogenous mass was found at the distal pancreas. The patient underwent en-block distal pancreatectomy with splenectomy with the presumptive diagnosis of cystic neoplasm of the pancreas. The tumor was well-circumscribed, encapsulated, 5.5 cm in the greatest dimension and showed typical papillary and pseudopapillary structures. Capsular invasion was seen on focal areas. The patient was not given any adjuvant therapy and shows no sign of disease after six months follow-up. It is important to differentiate this tumor from other pancreatic neoplasms because this neoplasm is amenable to cure after complete surgical resection even in cases with capsular invasion, unlike malignant tumors of the pancreas.

Pulmonary Lymphangioleiomyomatosis: A Rare Case

2014-09-01

Lymphangioleiomyomatosis is an uncommon lung disease primarily affecting women of childbearing age. It is characterized by the progressive proliferation and infiltration of smooth muscle-like cells, which lead to cystic destruction of the lung parenchyma; obstruction of airways, blood vessels, and lymphatics; and loss of pulmonary function. We present the case of a 46-year-old female patient with chest pain, cough, sputum, and dyspnea on exertion for three weeks. Minimal pneumothorax was noted, and the patient was referred to our center for further investigation and treatment. High-resolution computed tomography revealed numerous bilateral thin-walled air cysts and interstitial thickening affecting the central and peripheral part of the upper zone of the lung. We performed an open-lung biopsy to confirm lymphangioleiomyomatosis. Our aim is to discuss the pathogenesis and other lesions noted in the differential diagnosis of this rare disease.

Cytopathologic Diagnosis of Spontaneous Infarction of Fibroadenoma of the Breast

Neelam WADHWA, Richa JOSHI, Nidhi MANGAL, Nirupma Panikar KHAN, Mohit JOSHI — 2014-09-01

Infarction is an uncommon event in a fibroadenoma, which is the commonest benign tumor of the breast. Most often it occurs in pregnancy, lactation or is secondary to fine needle aspiration. Spontaneous infarction of a fibroadenoma in the absence of a predisposing condition is very rare. The cytopathologic features of infarction are necrosis and worrisome nuclear features, which are often misinterpreted as either inflammation or malignancy. We detail a report of accurate cytopathologic diagnosis of spontaneous infarction of fibroadenoma in a 17-year-old adolescent non pregnant girl. Careful attention to the cytopathologic clues like uniform thickness of the necrotic epithelial fragments, branching pattern reminiscent of the staghorn pattern despite atypical nuclear features and clinical details like young age of the patient and recent onset pain in a pre-existing lump helped arrive at the correct diagnosis and spared the patient of a radical excision. To the best of our knowledge, there are no earlier reports of correct cytopathologic diagnosis.