A Rare and Successfully Managed Complication of Stem Cell Transplantation in an Adult Patient With Sickle Cell Disease: Bone Marrow Necrosis.

Sickle cell disease is the most common genetic disorder in the Eastern Mediterranean region where our transplant center is located. Today, adult patients with sickle cell disease can also be successfully treated with allogeneic hematopoietic stem cell transplantation. Bone marrow necrosis is a rare and serious clinical condition. Herein, we present this complication for the first time in the literature, which developed in the course of allogeneic hematopoietic stem cell transplantation and was successfully managed with additional bone marrow support. The recognition, prevention, and management of this rare and potentially fatal complication, bone marrow necrosis, are vitally important, especially in regions with high prevalence of sickle cell disease.

Primary adrenal non-Hodgkin's lymphoma: report of two cases.

Primary adrenal lymphoma is very rare. It is characterized by a high incidence of bilateral adrenal involvement of diffuse large B-cell lymphoma. It can be diagnosed with endocrine evaluation, imaging studies and histopathological examination. We present two cases of primary adrenal lymphoma. One is a 74-year-old female patient with right primary adrenal lymphoma and the other is a 62-year-old male patient with bilateral primary adrenal lymphoma associated with normal adrenal function. In both cases, radiological features led to an initial misdiagnosis. The surgical exploration demonstrated masses invading the retroperitoneal space, and the biopsy revealed diffuse large B-cell lymphoma. In conclusion, primary adrenal lymphoma should be kept in mind in the differential diagnosis of adrenal masses. In cases of suspicious primary adrenal lymphoma, percutaneous computerized tomography or ultrasonography-guided needle biopsy can help to avoid unnecessary surgeries.

Immunohistochemical prognostic criteria in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare inheritable disease characterized by severe sun sensitivity and early development of skin cancers. We compared the expression of cell proliferation markers and cell cycle checkpoint regulators in squamous cell carcinomas (SCC) and basal cell carcinomas (BCC) from patients with and without XP. Immunostaining for p53, Ki-67, and proliferating cell nuclear antigen (PCNA) was determined in SCCs and BCCs from 18 XP patients and 30 controls. Nine of the 18 XP patients had SCC and BCC, and the other nine had only SCC. In the control group, 15 moderately differentiated SCCs and 15 BCCs were evaluated. Expressions of p53, Ki-67 and PCNA in XP and non-XP patients were assessed statistically by using the Chi-square method. Expression of Ki-67 and PCNA was found to be greater in SCC from XP patients than controls (P = 0.021 and P = 0.033, respectively). Expression of PCNA and p53 by BCCs was greater in XP patients (P < 0.001 and P = 0.027, respectively). There was a significant difference in Ki-67 (P < 0.001) and PCNA (P = 0.001) expression between the lesions of the XP patients who died during the follow up and XP patients who survived. In XP patients, SCCs with more than 10% Ki-67 expression and %50 PCNA expression have a poor prognosis. Our results suggest that increased Ki-67 and PCNA expression may be a predictor for recurrence of nonmelanocytic skin cancer and a poor prognosis.

Maspin, E-selectin, and P-selectin expressions in papillary thyroid carcinomas and their correlation with prognostic parameters.

Maspin is a serine protease inhibitor belonging to the serpin family, and is known as a tumor-suppressor protein. Maspin also exhibits an inhibitor effect on angiogenesis. Cell adhesion molecules such as E- and P-selectin are known to play an important role in the metastasis mechanism. We evaluated the expression of maspin, E- and P-selectin in 74 papillary thyroid carcinomas, 19 of which had lymph node metastases, and statistically analyzed the relationship between these three proteins and their relation with prognostic factors. Positive correlations were found for maspin positivity and lymph node metastases; thyroid capsule invasion and perithyroidal soft tissue invasion; E-selectin positivity and lymph node metastases, lymphovascular invasion and perithyroidal soft tissue invasion; and P-selectin positivity and lymph node metastases and lymphovascular invasion (p < 0.05). Statistically significant correlations were also found between maspin, E- and P-selectin expressions with each other and with tumor stage (p < 0.05). Inactive cytoplasmic maspin cannot act as a tumor suppressor. Expression of E- and P-selectins in tumor cells facilitates the occurrence of metastases, lymphovascular invasion, and perithyroidal soft tissue invasion. Further studies, in particular molecular investigations, are needed to reveal the detailed interactions between maspin, E-selectin, and P-selectin expression.

Synchronous GIST with osteoclast-like giant cells and a well-differentiated neuroendocrine tumor in Ampula Vateri: coexistence of two extremely rare entities.

Mesenchymal tumors of the gastrointestinal system with variable histopathological appearances and constant expression of CD117 are known as gastrointestinal stromal tumors (GISTs). Neuroendocrine tumors may be seen in the gastrointestinal system and other organ systems of the body. We report a 44-year-old male patient with a 6.5 x 3 x 6cm mass located in the Ampulla of Vater. Histopathologic examination revealed a GIST with a marked nuclear pleomorphism and a high mitotic rate, and that was rich in osteoclast-like giant cells (OGC). Immunohistochemically, GIST was positive for CD117, while OGCs were negative for CD117 and positive for CD68 and alpha1-antitrypsin. There was also found a well-differentiated neuroendocrine tumor near the GIST, in the serosal aspect of the duodenum at the point of the Ampulla of Vater. This second tumor was 20mm in diameter, and was relatively well circumscribed with few glands invading the GIST. This tumor was positive for synaptophysin and chromogranin. Neither mitosis nor vascular invasion was observed. The patient had no familial history or clinical manifestations of neurofibromatosis. This case presents the unique synchronous existence of two extremely rare entities, a GIST with OGC and a well-differentiated neuroendocrine tumor, both located in the Ampulla of Vater.

Diagnostic accuracy of toluidine blue-stained wet films in effusion cytology.

OBJECTIVE: To evaluate the usefulness of toluidine blue-stained wet films in the preliminary cytologic evaluation of serous effusions by means of specificity, sensitivity, and positive and negative predictive value. STUDY DESIGN: One hundred seventy-six samples consisting of 122 pleural and pericardial effusions and 54 peritoneal effusions from 160 patients were included in the study. A toluidine blue-stained wet film of each sample was evaluated, and diagnoses were compared with the diagnoses by conventional smears and cell blocks on the same sample. RESULTS: The sensitivity of wet films was 69%, 68% in pleural and pericardial effusions and peritoneal effusions, respectively, and the specificity of wet films was 93%, 92% in pleural and pericardial effusions and peritoneal effusions, respectively. Positive predictive values of smears alone were 78% and 75%; negative predictive values of smears alone were 96% and 95% in pleural and pericardial effusions and peritoneal effusions, respectively. CONCLUSION: Preliminary cytologic evaluation of serous effusions with toluidine blue-stained wet films is simple and economical. It provides the opportunity to plan additional procedures for the samples.

Primary primitive neuroectodermal tumor of the kidney: a case report.

There are nearly 50 PNET cases in the literature with primary renal localization. The mean age for renal PNET is 28 but it can be seen in a wide range between 4 and 69 years. In this atypical localization PNET may be mistaken with a variety of small round cell tumors, particularly with blastema predominant Wilms' tumor and due to its distinctive prognostic and therapeutic features differential diagnosis is very important. Immunohistochemical studies are useful in discriminating PNET from other renal small round cell tumors. Renal PNETs tend to metastasize at early stages and they have a high rate of recurrence. Our case is a 45-year-old male presented with left flank pain and hematuria. In computerized tomography a mass in left kidney was observed and nephrectomy was performed. Histopathologic examination revealed a small round cell tumor with rosettes and pseudorosettes. Immunohistochemically the lesion was diffuse strong positive with CD99 and NSE, negative with LCA, pancytokeratin, vimentin, desmin, smooth muscle actin, chromogranine A and S-100. At the time of diagnosis the pathologic stage of the tumor was T1aN0Mx. The patient did not take any further therapy and in 1-year follow-up no local recurrence or distant metastasize occurred.

Insular carcinoma of the thyroid with uncommon cytologic features: anisokaryotic cells and microfollicles containing dense colloid.

Insular carcinoma of the thyroid is a rare neoplasm, constituting less than 5% of all thyroid tumors. It was Carcangiu et al. who first described this tumor, which exhibits an intermediate biologic behavior between well-differentiated and undifferentiated follicular carcinomas, as a distinct clinicopathologic entity. A 63-year-old female patient with thyroid enlargement was admitted to our institution. Thyroid ultrasonography revealed a 5x4x3cm solid nodule within the right thyroid lobe. The fine needle aspiration was highly cellular; there were individual cells with naked nuclei, loose aggregates, cohesive clusters of follicular cells and infrequent microfollicles with round-oval nuclei containing finely granular chromatin, and scant cytoplasm. There were two uncommon findings not previously reported in the literature. The first one is anisokaryotic nuclei, and the second one is the presence of dense colloid in the center of microfollicles. The aspiration biopsy was reported as malignant. The patient underwent bilateral total thyroidectomy. Histopathologically, the lesion was diagnosed as insular carcinoma. We believe that in addition to the previously described cytopathologic findings, microfollicles with dense colloid core and anisokaryosis may be indicators of insular carcinoma in thyroid FNACs.

Subscapular elastofibroma intermingled with adipose tissue: variant type of elastofibroma or lipoma?

Elastofibroma is a rare entity most commonly seen in subscapular region. Elastofibrolipoma was first described by De Nictolis et al (Am J Surg Pathol. 1995;19:364-367) as a capsulated mass, composed of mature fat, abnormal elastic fibers, and connective tissue, at the anterior mediastinum. A 57-year-old woman with a periscapular pain and a mass at the left subscapular region was admitted at the department of thoracic surgery. Histologic sections of the well-circumscribed 6.5 x 5 x 3.5-cm rubbery mass revealed a collagenous stroma containing eosinophilic globules and fragmented fibers intermixed with mature adipose tissue surrounded by a thin fibrous capsule. The elastic nature of these eosinophilic fibers and globules was confirmed with Verhoeff's elastic stain. The lesion was diagnosed as elastofibrolipoma, a recently recognized lesion with an unclear origin. Here we discuss if it is a variant of elastofibroma or lipoma.

The role of cytokeratin 19 in the differential diagnosis of true papillary carcinoma of thyroid and papillary carcinoma-like changes in Graves' disease.

Graves' disease is an autoimmune disease predominantly seen in females. All types of thyroid cancers may co-exist with Graves' disease but papillary carcinoma is the most frequent. Vesicular nuclei, nuclear grooves, and papillary formations that may be seen in Graves' disease may lead the pathologist to an overdiagnosis of papillary carcinoma. The differential diagnosis between a true papillary carcinoma and foci mimicking papillary carcinoma in Graves' disease may be challenging by light microscopic features only. This study is designed to determine whether CK19 is effective in the discrimination between the true papillary carcinoma of thyroid and foci resembling papillary carcinoma in Graves' disease. Twenty-five cases with papillary carcinoma and 25 cases with Graves' disease containing foci resembling papillary carcinoma were included in the study. All 25 cases with papillary carcinoma stained positive with CK19, whereas only six of 25 cases with Graves' disease showed weak staining, and the remaining 19 cases were completely negative. It is known that CK19 may show faint staining in benign thyroid lesions such as adenomas. Staining pattern with CK19 together with histopathological findings may be helpful in the differential diagnosis between foci mimicking papillary carcinoma and true papillary carcinoma in Graves' disease.

Nasal angiomyolipoma.

Angiomyolipomas (AMLs) are hamartomatous lesions containing smooth muscle, vasculature and mature adipose tissue. AML occurs most frequently in the kidneys, with the liver being the second commonest site of involvement. Other localizations for AML are extremely rare and, to our knowledge, only six cases of AML of the nasal cavity have been reported to date. Our case involved a 52-year-old male who presented with a history of snoring and obstruction of the left nasal cavity. Physical examination revealed a 3-cm polypoid mass in the left nasal cavity, which was excised surgically. Histopathologic examination revealed that the lesion was composed of smooth muscle bundles, mature adipose tissue and blood vessels of different sizes. No epitheloid smooth muscle cells were observed and HMB-45 staining was negative. In conclusion, although nasal AML is a rare lesion, it should be considered in the differential diagnosis of polypoid nasal masses, especially when the mass occurs unilaterally.

TTF-1 and surfactant-B as co-adjuvants in the diagnosis of lung adenocarcinoma and pleural mesothelioma.

Primary lung adenocarcinomas and metastatic adenocarcinomas may show a great morphologic resemblance to malignant mesothelioma. There are numerous immunohistochemical markers being used, but none of them were proved to be effective enough to reach a certain diagnosis. The current study was performed to evaluate the utility of thyroid transcription factor-1 (TTF-1) and surfactant protein-B (SP-B) expression in the differential diagnosis between lung adenocarcinomas and pleural mesotheliomas. In this retrospective study, TTF-1 and SP-B were applied to 30 cases with adenocarcinoma and 15 cases with pleural mesothelioma, immunohistochemically, using an avidin-biotin detection system. Twenty percent of adenocarcinomas and 13.3% of pleural mesothelioma stained positive for SP-B. TTF-1 stained 24 of the 30 adenocarcinomas (80%) and none of the 15 mesotheliomas (0%). TTF-1 positivity in adenocarcinomas was found to be statistically significant, while SP-B had no important practical value either used alone or in combination with TTF-1. There was no statistically significant correlation between the differentiation level of adenocarcinomas and TTF-1 staining pattern. In conclusion, we believe that TTF-1 may be helpful in distinguishing lung adenocarcinoma from pleural mesothelioma.

Cutaneous involvement in Hodgkin's lymphoma: report of two cases.

Hodgkin's lymphoma (HL) comprises 20 to 30% of all lymphomas. Skin involvement is almost always secondary to visceral or nodal involvement. Secondary cutaneous HL is rare, occurring in only 0.5 to 3.4% of the cases. Herein we report two cases of skin involvement in Hodgkin's disease. One was a 25-year-old female admitted with a draining sinus in the neck. The other was a 19-year-old female admitted with a neck mass and skin papules on her chest and arm. Skin involvement may antecede or can be seen during the course of HL. Better understanding of such cutaneous involvement, which occasionally may be the initial sign of HL, is needed, and a biopsy of any suspicious skin lesion should be considered.

Hydatid cyst of the thyroid gland in a child.

The hydatid cyst tend to form in the liver or lung but may be found in any organ of the body, including brain, heart, and bones. Thyroid gland involvement is rather rare. Cyst leakage or rupture may even associated with severe allergic reaction to parasite antigens, and may cause anaphylactoid reactions. Herein we reported an additional case of hydatid cyst of the thyroid gland that occurred in a 9-year-old boy who admitted with a painless and cystic thyroid mass. Hemithyroidectomy was performed, and histopathology confirmed the diagnosis of hydatid cyst. Diagnosis of that rare clinical entity is unlikely prior to surgical excision and histopathologic examination. Despite this fact, hydatid disease of the thyroid should be remembered in the differential diagnosis of the cystic thyroid masses, and a high index of suspicion is required.

Cutaneous undifferentiated small (Merkel) cell carcinoma, that developed synchronously with multiple actinic keratoses, squamous cell carcinomas and basal cell carcinoma.

Merkel Cell Carcinoma (MCC) is an uncommon undifferentiated neuroendocrine tumor, arising in skin mainly on sun-exposed areas. We present an unusual case of primary cutaneous undifferentiated small cell carcinoma that co-existed with six other lesions; 2 actinic keratoses, 3 squamous-cell carcinomas and a basal-cell carcinoma. HE stained sections revealed MCC located in the mid-dermis, co-existing with severe actinic keratosis. Immunohistochemically, the tumor cells reacted to cytokeratin 20, epithelial membrane antigen, chromogranin and neuron specific enolase. This is an unusual case of cutaneous MCC co-existing with six other different lesions. The concurrent development of MCC, squamous-cell and basal-cell carcinoma in the same patient indicates the pluripotent epidermal stem cell origin of these tumors. Further research is needed to enlighten the factors inducing this divergent differentiation.

Comparative effect of intra-articular administration of hyaluronan and/or cortisone with evaluation of malondialdehyde on degenerative osteoarthritis of the rabbit's knee.

Hyaluronan and cortisone have controversial and an important role in the healing of degenerative osteoarthritis. The purpose of the research was to compare individual and combined effects of hyaluronan and cortisone on the healing of degenerative osteoarthritis and to determine the serum malondialdehyde level as a lipid peroxidation marker. A rabbit model was used in which a degenerative osteoarthritis was created in the articular cartilage by resection of anterior cruciate ligament. The rabbits divided into three groups namely were injected with hyaluronan (group A) and cortisone (group B) at days 31, 38 and 45. Cortisone at day 31 and hyaluronan at days 38 and 45 were injected to the third group (group C). We obtained blood samples from each rabbit to determine the malondialdehyde levels at days 1, 30, and 52. At day 52, 21 rabbits were sacrificed. In biopsies obtained from treated and untreated knees articular cartilage degeneration was examined by light microscopy. Histopathologically the healing rate was significantly higher in group C than the other groups. Degeneration decreased 72% in group A, 52% in group B and 88% in group C at day 22. Malondialdehyde levels were 2.056 +/- 0.37 in the control group, 1.94 +/- 0.54 in group A, 1.98 +/- 0.37 in group B and 1.55 +/- 0.41 in goup C. The malondialdehyde levels of group A and B were less than the control group (statistically insignificant, p > 0.05). But, there were statistically significant values between control group and group C (p < 0.05). The results showed that the combination of cortisone and hyaluronan is the most effective in the treatment of cartilage degeneration in the course of the ostearthritis and the malondialdehyde levels are correlated with the severity of degeneration.

Histological features in routine tonsillectomy specimens: the presence and the proportion of mesenchymal tissues and seromucinous glands.

Tonsillectomy is a frequently performed operation but there is little information about the histological features of a tonsillectomy specimen. In this study, we re-evaluated archival materials of 1220 cases who underwent tonsillectomy because of hyperplastic tonsils. Haematoxylin and eosin sections of the cases were re-examined and the presence and the proportion of mesenchymal tissues (skeletal muscle, cartilage, fat, bone) and seromucinous glands were noted as focal, multifocal or abundant. The incidence of skeletal muscle was 89 per cent (1085 cases; 206 focal, 465 multifocal, 414 abundant), seromucinous glands 35 per cent (429 cases; 236 focal, 134 multifocal, 59 abundant), fat 21 per cent (251 cases; 208 focal, 43 multifocal), cartilage three per cent (31 cases), and bone one per cent (seven cases). Also in 165 cases (14 per cent) skeletal muscle, in 12 cases (one per cent) was seromucinous glands, in eight cases (one per cent) was cartilage, in seven cases (one per cent) fat, and in four cases (less than one per cent) bone were found between hyperplastic lymphoid tissue. It can be concluded that mesenchymal tissues (skeletal muscle, cartilage, fat, bone) and seromucinous glands may be seen in different proportions in routine tonsillectomy specimens.

Diagnostic utility of cytokeratin 19 expression in multinodular goiter with papillary areas and papillary carcinoma of thyroid.

The most common benign lesion of thyroid, multinodular goiter, may mimic papillary carcinoma if it contains papillary areas. Although it is usually not very difficult to distinguish between these benign and malignant lesions, some cases may be problematic in differential diagnosis. In these cases, we decided to use cytokeratin 19 (CK19), which is shown to be effective in discriminating papillary carcinoma from follicular carcinoma of thyroid, and we also evaluated the immunoreactivity of CK19 in follicular adenomas. Twenty-five cases of multinodular goiter showing papillary formations, 25 cases of papillary thyroid carcinoma, and 15 cases of follicular adenoma were selected from archives of our institution. Immunohistochemical staining for CK19 was performed on deparaffinized sections. Diffuse and intense CK19 positivity was found in the cells of all papillary carcinomas. In the multinodular goiter group, 20 of 25 cases showed no staining while the remaining 5 were focally reactive with CK19. Three of the five were thought to be false positive owing to hemorrhage. Weak and focal CK19 staining was seen in some follicular adenomas. Our observations suggest that the staining features of CK19 may be helpful in differential diagnosis between papillary carcinoma and multinodular goiter showing papillary areas. Focal and pale staining for CK19 may be seen in multinodular goiter with papillary formations, and this feature should be considered in evaluation.