Incidence, Histopathological Features and Differential Diagnosis of Cutaneous Graft Versus Host Disease in Allogeneic Bone Marrow Transplantation.

OBJECTIVES: Hematopoietic stem cell transplantation by allogeneic bone marrow transplantation is a method used in the treatment of various genetic, immunological disorders, hematologic and solid organ malignancies. Graft versus Host Disease is one of the major and fatal complications of allogeneic bone marrow transplantation. It is a systemic disease affecting five main areas: skin, gastrointestinal tract, liver, lung and hematopoietic system. Diagnosis of cutaneous Graft versus Host Disease is made by the correlation between clinical and histopathological findings of the patient. The present study aims to investigate the incidence of cutaneous graft versus Host Disease in allogeneic bone marrow transplantation patients in our center, to discuss the histopathological features and differential diagnosis of cutaneous graft versus Host Disease in the light of the literature. METHODS: The pathology slides of allogeneic bone marrow transplantation patients who were diagnosed as graft versus Host Disease in our pathology department between January 2015 and January 2019 were re-evaluated. Epidermal and dermal histomorphological findings of the disease were classified; the patients' clinical and demographic information was obtained from the files. The incidence of cutaneous Graft versusHost Disease was calculated. RESULTS: In our center, between January 2015 and January 2019, 273 pediatric and 100 adult patients underwent allogeneic and 181 autologous bone marrow transplantation. Twenty-three patients who underwent allogeneic bone marrow transplantation had cutaneous Graft versus Host Disease whereas and 21 patients had gastrointestinal Graft versus Host Disease. The incidence of cutaneous and gastrointestinal Graft versus Host Disease was 16.1% whereas the incidence of cutaneous Graft versus Host Disease was 8.42%. The most common clinical differential diagnosis of cutaneous Graft versus Host Disease was drug reaction (74%). The most common epidermal histomorphologic finding in our cases was keratinocyte necrosis (87%). In our cases, the most common epidermal histomorphologic finding was keratinocyte necrosis (87%). This was followed by vacuolar degeneration in basal keratinocytes (63%), acanthosis and spongiosis (61%), respectively. The most common finding in the dermis was pigment incontinence (59%). Of the patients with Graft versus Host Disease, 56% had transplantation from unrelated donors, whereas 44% of them had transplantation from their relatives. CONCLUSION: Cutaneous Graft versus Host Disease is a common complication of allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and has a significant negative impact on the patient's quality of life. Dermatological early recognition of the disease; histopathological evaluation and verification with differential diagnosis plays a key role in preventing patient morbidity and mortality.

Diagnostic cytological features and differential diagnosis of subacute granulomatous (De Quervain's) thyroiditis.

BACKGROUND: The aims of the study are to identify the diagnostic cytological features of subacute granulomatous thyroiditis (SGT), to compare our results with previous literature studies, and to investigate the cytological changes in SGT that mimic other thyroid lesions. METHODS: This retrospective study was conducted with 69 cases. The cytology slides were re-evaluated. The diagnostic cytomorphological features of the disease were identified. The results were compared with the literature. Differential diagnosis of the disease is discussed with the results obtained. RESULTS: The diagnostic cytological features consisted of lymphocytes, multinucleated giant cells, loose epithelioid histiocyte groups, granulomas, isolated epithelioid histiocytes, colloid, and neutrophil leukocytes. The highest degree of concordance between our results and the published literature was the presence of giant cells while the lowest was for microfollicles. Some reactive cytological features of SGT were similar to other benign or malignant diseases of the thyroid. CONCLUSION: SGT is a rare and self-limiting disease. Cytological features are not specific. The diagnosis should be confirmed by clinical and laboratory results. Reactive atypia in the early phase of the disease and microfollicles in the late phase may lead to a false cytological diagnosis, thus resulting in unnecessary resection. To prevent such misdiagnoses, cytopathologists should be aware of the reactive cytological changes in this disorder.

Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests?

BACKGROUND/AIMS: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Effects of an Additional Liquid Based Cytology Prepate on Cytological Diagnosis in High-Risk HPV Positive, PaP Test Negative Cases.

OBJECTIVES: To investigate the effects of a second cytology preparation on cytological diagnosis in high-risk HPV positive and PaP smear-negative cases. METHODS: This retrospective study was conducted with 57 cases who underwent cytological evaluation and cotest in our center in 2016-2017. All of these cases were high-risk HPV positive, PaP smear-negative and had a second preparation. All preparations were re-evaluated by a cytopathologist and a pathologist. Twenty-five of the cases who had a positive diagnosis in the second preparation had a cervical biopsy. RESULTS: In 46 (80%) of the cases, the cytological diagnosis was the same and negative in the first and second preparations. Second preparations of 11 cases (19.2%) were positive. Twenty of 25 patients (77%) with cervical biopsy had premalignant lesion. CONCLUSION: In high-risk HPV positive and PaP smear-negative cases, patient management is different from cases where these two tests are positive together. According to our results, 19.2% of high-risk HPV positive and PaP smear-negative cases were given positive cytological diagnosis by second cytology preparation. Biopsy results support our cytological findings. The incidence of positive cytological diagnosis increases in PaP smear with the second preparation. With this protocol, patient management changes, follow-up time and number can be reduced.

Telecytology: Is it possible with smartphone images?

INTRODUCTION: This study aimed to discuss smartphone usage in telecytology and determine intraobserver concordance between microscopic cytopathological diagnoses and diagnoses derived via static smartphone images. METHODS: The study was conducted with 172 cytologic material. A pathologist captured static images of the cytology slides from the ocular lens of a microscope using a smartphone. The images were transferred via WhatsApp® to a cytopathologist working in another center who made all the microscopic cytopathological diagnoses 5-27 months ago. The cytopathologist diagnosed images on a smartphone without knowledge of their previous microscopic diagnoses. The Kappa agreement between microscopic cytopathological diagnoses and smartphone image diagnoses was determined. RESULTS: The average image capturing, transfer, and remote cytopathological diagnostic time for one case was 6.20 minutes. The percentage of cases whose microscopic and smartphone image diagnoses were concordant was 84.30%, and the percentage of those whose diagnoses were discordant was 15.69%. The highest Kappa agreement was observed in endoscopic ultrasound-guided fine needle aspiration (1.000), and the lowest agreement was observed in urine cytology (0.665). Patient management changed with smart phone image diagnoses at 11.04%. CONCLUSIONS: This study showed that easy, fast, and high-quality image capturing and transfer is possible from cytology slides using smartphones. The intraobserver Kappa agreement between the microscopic cytopathological diagnoses and remote smartphone image diagnoses was high. It was found that remote diagnosis due to difficulties in telecytology might change patient management. The developments in the smartphone camera technology and transfer software make them efficient telepathology and telecytology tools.

Role of biochemistry and cytological analysis of cyst fluid for the differential diagnosis of pancreatic cysts: A retrospective cohort study.

BACKGROUND: Management of pancreatic cysts is based on neoplastic-nonneoplastic discrimination. Endoscopic ultrasound (EUS) enables to differentiate neoplastic-nonneoplastic lesions and also allows fine-needle aspiration (FNA). In this study, we aim to assess feasibility and clinical relevance of cytological and biochemical analysis in differential diagnosis of cystic pancreatic lesions in patients who had undergone endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) due to pancreatic cysts. METHODS: Participants were 96 patients who had undergone EUS-FNA for differential diagnosis of pancreatic cysts. Pancreatic cysts were classified as benign-mucinous, nonmucinous, and malignant according to patient history, physical examination, EUS appearance, and cystic fluid assessment. Tumor markers (CEA, CA(cancer antigens) 72.4, CA 19-9) , amylase, lipase and cytological assesment were compared between 3 different groups. Receiver-operating characteristics (ROC) curves were constructed to identify appropriate cut-off values. RESULTS: Fluid CEA and CA 72.4 levels for benign-mucinous and malignant cysts were significantly higher than for nonmucinous cysts (P ≤ 0.04). A cut-off CEA level of 207 ng/mL differentiated mucinous etiology with a sensitivity of 72.7%, specificity of 97.7%, and accuracy of 89.5%. The sensitivity, specificity, and accuracy of the CA 72.4 cut-off level of 3.32 ng/mL were 80%, 69.5%, and 73.6%, respectively. CONCLUSION: Cyst fluid CEA and CA 72.4 levels have a high accuracy in discriminating mucinous from nonmucinous cysts. When combined with cytology their accuracy rate increases.

Rare pancreas tumor mimicking adenocarcinoma: Extramedullary plasmacytoma.

Neoplastic proliferation of plasma cells is called plasma cell dyscrasias, and these neoplasms can present as a solitary neoplasm or multiple myeloma. Extramedullary plasmacytoma, in particular pancreatic plasmacytoma, is a rare manifestation of multiple myeloma. Although computerized tomography is useful for the diagnosis of extramedullary plasmacytoma, there are no specific radiologic markers that distinguish it from adenocarcinoma. Histological confirmation by biopsy is necessary for accurate diagnosis and management of the tumor. Endosonography is the most sensitive method for the diagnosis of pancreatic tumors, and the use of fine needle aspiration by endosonography is associated with a lower risk for malignant seeding and complications. Here, we report a case of pancreatic plasmacytoma in newly identified multiple myeloma as diagnosed by endosonography. Endosonography is a reliable and rapid method for the diagnosis of extramedullary plasmacytoma. Therefore, endosonographic fine needle aspiration should be the first choice for histological evaluation when pancreatic plasmacytoma is suspected. Ideally, the pathology would be performed at the same site as endosonographic biopsy.

Effects of palatine bone denudation repair with periosteal graft on maxillary growth: an experimental study in rats.

BACKGROUND: The long-term goal of cleft palate repair is to provide normal maxillary growth and speech capacity. However, most surgical repairs of cleft palate result in areas of bone denudation on lateral aspects of the hard palate. It is widely acknowledged that palatal bone denudation and subsequent scar contracture resulting from cleft palate surgery can inhibit maxillary growth. METHOD: This study is designed to investigate the effect of the periosteum on growth patterns of the maxilla. A total of 32 three-week-old Sprague-Dawley rats were randomly divided into a control group and three experimental groups: a mucosa excision group, a mucosa-periosteum excision group and a periosteal graft group. Nine weeks postoperatively the skulls were prepared for study and palatal widths and lengths were determined. The experimental groups were investigated for various histological changes. RESULTS: There was no statistically significant difference for the maxillary measurements (palatal width and length) between the mucosa excision group and the periosteal graft group when compared with the control group. However, the mucosa-periosteum excision group compared to the control indicated a statistically significant decrease in the same measurements. There was also a statistically significant difference for the maxillary measurements between the periosteal graft group and the mucosa-periosteum excision group. It was demonstrated histologically that the density of the Sharpey's fibres and periodontal scar tissue showed a slight increase in the mucosa excision group and the periosteal graft group compared with the control group. In the mucosa-periosteum excision group, the density increased significantly as expected. CONCLUSIONS: All of these findings testify that retaining the periosteum or replacement with a periosteum graft after surgery can prevent the inhibition of maxillary growth.

Reevaluation of negative cone biopsy results after a positive cervical biopsy finding.

OBJECTIVE: This study aimed to evaluate and reexamine materials of the patients with cervical biopsy revealing cervical intraepithelial neoplasia and their cone biopsies revealing no lesion. MATERIALS AND METHODS: Twenty-five patients with cervical biopsy revealing cervical intraepithelial neoplasia and cone biopsies revealing no lesion among 202 patients who had undergone cervical conization after colposcopically derived cervical biopsy between 2005 and 2011 were included in this study. Ki67 and P16 were applied to the all biopsy slides. The conization blocks of patients whose reevaluation results of the original biopsy slides were positive were completely sectioned to reexamine the presence of any lesion, and suspicious areas were stained with Ki67 and P16. RESULTS: Of the 25 patients' punch biopsies, no lesion was detected in 13 patients. The false positivity of first punch biopsy (52%) was the main reason for negative cone biopsy result after positive punch biopsy. Punch biopsies of the other 12 patients confirmed the lesions previously diagnosed. The detailed examination of conization specimens of the latter group showed 3 new low-grade cervical intraepithelial neoplasia, which had not been identified before. CONCLUSIONS: Discordance between cervical biopsy findings and cervical conization findings could result from misdiagnosis of cervical biopsy, failure in preparation of the whole conization material, and technical difficulties of conization. Ki67 and P16 staining can be used in such cases to clarify the diagnosis.

LSIL/ASC-H (LSIL-H) in cervicovaginal smear: histopathological outcomes and clinical significance.

OBJECTIVE: Conventional Pap smears exhibiting unequivocal features of 'low grade squamous intraepithelial lesion' (LSIL) are occasionally mixed with some cells suspicious for, but not diagnostic of 'high grade squamous intraepithelial lesion' (HSIL) on daily routine. The 2001 Bethesda System does not address the significance of such cytological entities. We have referred to these changes in our laboratory as'LSIL, atypical squamous cells cannot exclude HSIL' (LSIL/ASC-H). In this study, we aimed to compare the cytology and biopsy results of LSIL/ ASC-H to LSIL, ASC-H and HSIL. MATERIAL AND METHOD: Out of 37884 cases which were evaluated between 2005-2009 in our laboratory, cases interpreted as LSIL, LSIL/ ASC-H, HSIL and ASC-H were reevaluated and 153 cases for which biopsy materials were available were selected. RESULTS: The rate of histological CIN2 or worse associated with LSIL/ ASC-H (45%) was between the rates of LSIL (10%) and HSIL (65%), but not significantly different from ASC-H (50%). However, LSIL/ ASC-H was more frequently associated with a definitive histological diagnosis of any CIN2 than ASC-H (30% vs. 8%). CONCLUSION: Based on our results, we recommend LSIL/ASC-H to be added to Bethesda System, and Pap test cases of LSIL/ASC-H may need to be clinically followed-up in a manner similar to ASC-H, i.e., with colposcopy for all patients.

Metastatic ovarian malignant melanoma with no obvious primary.

The differential diagnosis of metastatic ovarian malignant melanoma from primary ovarian tumors is a significant challenge, particularly if there is no obvious primary site. A 39-year-old patient with bilateral ovarian malignant melanoma presented as stage IV primary ovarian tumor, with metastases in the omentum and spleen. She underwent a total abdominal hysterectomy and bilateral salpingo-oopherectomy with infracolic omentectomy and splenectomy. The diagnosis on examination of frozen sections was inconclusive. The final diagnosis was made by immunohistochemistry. The sections showed positive staining with HMB-45, vimentin, S-100, and no staining for cytoceratin, inhibin, calretinin and caldesmon. After the operation, the MRI at the 14(th) postoperative day revealed metastatic lesions in the vertebrae, sacrum, bilateral humerus and femur and in the cerebral cortex, together with edema and hemorrhagic foci. The patient stayed in the intensive care unit for 12 weeks until her death due to cardio-respiratory arrest. This case highlights the clinical fact that metastatic malignant melanoma may mimic primary ovarian tumor with an occult or regressed primary. Both the standard pre-operative imaging modalities (such as CT, MRI) and the histo-pathologic examination of the frozen sections may be inconclusive in the differentiation of ovarian melanoma from epithelial ovarian malignancies. The final diagnosis could be established by immunohistochemistry. Intra-abdominal debulking surgery would not prolong the survival of metastatic ovarian melanoma because of the occult or rapid metastasis to the extra abdominal sites of the tumor.

Congenital pulmonary fibrosarcoma in a newborn with hypoglycemia and respiratory distress: case report.

Although primary bronchopulmonary fibrosarcoma is a rare tumor, it may be characterized by the symptoms of acute respiratory distress occurring during the first moments of life in a newborn. It is one of the leading congenital malignant neoplasms of the lung, but is considered a borderline tumor since its biological behavior is much more favorable than that of adult fibrosarcomas. In the absence of metastases, complete resection is curative. Histopathological diagnosis is not simple, as the microscopic characteristics may be confused with benign fibromatosis or malignant mesenchymal neoplasms. In this case report, we present a case of congenital pulmonary spindle cell tumor showing the features of fibrosarcoma, and we discuss the differential diagnosis of spindle cell lesions localized within the thorax.

An infantile leiomyosarcoma that metastasized from the small intestine to the adrenal gland.

In the literature, there is no reported pediatric leiomyosarcoma case that has metastasized from the small intestine to the adrenal gland. A 10-year-old boy who had anemia and weight loss over 2 years presented with abdominal pain that began 1 week previously. Radiologic examination revealed bilateral adrenal tumors. At the time of surgery, the terminal ileum was resected and a tru-cut biopsy was done from the right adrenal mass. The pathology report was leiomyosarcoma for both of the resection and tru-cut specimens. We present an intestinal leiomyosarcoma that metastasized from the small intestine to both adrenal glands with clinical, morphologic, and immunohistochemical studies with a literature review.

Iniencephaly with mediastinal bronchogenic cyst: A case report.

OBJECTIVE: Iniencephaly is a rare neural tube defectwith consisting of a defect in the occipital bone,spina bifida of many vertebrae, and retroflexion of the head on the spine. In majorty of cases it is a le-\thal condition. METHODS: We present the first case of iniencephalywith large bronchogenic cyst diagnosed prenatally. RESULTS: At 19 week's gestation showed that fetalcardiac activity was present with normal placentaand amniotic fluid, fetus had occipital bone defect, anencephaly, retroflexion of the head, abnormally short cervicothoracic spine and posterior mediastinal unilocular anechoic cyst. Therapeutic abortion was induced. CONCLUSION: Iniencephaly is a rare condition during prenatal life. When diagnosed early in pregnancy amultidisciplinary approach is firmly suggested.