Hülya Öztürk

The bone marrow aspirate and biopsy in the diagnosis of unsuspected nonhematologic malignancy: a clinical study of 19 cases.

BackgroundAlthough bone marrow metastases can be found commonly in some malignant tumors, diagnosing a nonhematologic malignancy from marrow is not a usual event.MethodsTo underscore the value of bone marrow aspiration and biopsy as a short cut in establishing a diagnosis for disseminated tumors, we reviewed 19 patients with nonhematologic malignancies who initially had diagnosis from bone marrow.ResultsThe main indications for bone marrow examination were microangiopathic hemolytic anemia (MAHA), leukoerythroblastosis (LEB) and unexplained cytopenias. Bone marrow aspiration was not diagnostic due to dry tap or inadequate material in 6 cases. Biopsy results were parallel to the cytological ones in all cases except one; however a meticulous second examination of the biopsy confirmed the cytologic diagnosis in this patient too. The most common histologic subtype was adenocarcinoma, and after all the clinical and laboratory evaluations, the primary focus was disclosed definitively in ten patients (5 stomach, 3 prostate, 1 lung, 1 muscle) and probably in four patients (3 gastrointestinal tract, 1 lung). All work up failed in five patients and these cases were classified as tumor of unknown origin (TUO).ConclusionOur series showed that anemia, thrombocytopenia, elevated red cell distribution width (RDW) and hypoproteinemia formed a uniform tetrad in patients with disseminated tumors that were diagnosed via bone marrow examination. The prognosis of patients was very poor and survivals were only a few days or weeks (except for 4 patients whose survivals were longer). We concluded that MAHA, LEB and unexplained cytopenias are strong indicators of the necessity of bone marrow examination. Because of the very short survival of many patients, all investigational procedures should be judged in view of their rationality, and should be focused on treatable primary tumors.

Expression of cyclin D1 in normal, hyperplastic and neoplastic endometrium and its correlation with Ki-67 and clinicopathological variables

MethodsWe investigated cyclin D1 expression in proliferative endometrium, endometrial hyperplasia and endometrioid adenocarcinoma, and examined the correlation of cyclin D1 expression with Ki67 as a cell proliferation associated marker. Immunohistochemical expression of cyclin D1 and Ki67 were studied in 30 cases with endometrial carcinoma, 14 cases with atypical hyperplasia, 15 cases with simple hyperplasia and 30 cases with proliferative endometrium.ResultsOne out of 30 patients (3.3%) with proliferative endometrium, 1 out of 14 patients (7.1%) with atypical hyperplasia, and 8 out of 30 patients (26.6%) with endometrial carcinoma were found to have immunoreactivity to cyclin D1. All cases of simple hyperplasia had negative staining for cyclin D1. A positive immunoreaction for Ki67 was obtained in all cases. Statistically significant difference was found in cyclin D1 immunoreactivity between both proliferative endometrium and adenocarcinoma, and simple hyperplasia and adenocarcinoma (p<0.05). In patients with adenocarcinoma, cyclin D1 immunoreactive cases had higher mean Ki67 values compared with the non-immunoreactive ones (p<0.05). Ki67 and cyclin D1 immunoreactivity had no impact on overall survival. Univariate analysis revealed a significant relationship between survival and grade and stage (p<0.01). Cyclin D1 expression was not correlated with age, depth of myometrial invasion, lymphovascular space involvement, grade, lymph node metastasis and stage.ConclusionCyclin D1 expression in endometrial carcinoma is higher than proliferative endometrium and simple hyperplasia. These findings support that cyclin D1 may play a role in endometrial carcinogenesis.

Angiogenesis in Endometrial Carcinoma: Correlation with Survival and Clinicopathologic Risk Factors

Association among angiogenesis, survival and clinicopathologic parameters in endometrial carcinoma was evaluated. Sixty patients who had been diagnosed as endometrial carcinoma, from 1993 to 1998, were included in the study. All patients had been surgically staged with bilateral pelvic and para-aortic lymph node dissection. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. The area with the most intensified microvasculature was determined under low-power (×100) magnification, and the microvessel count of this area under high-power (×200) magnification was determined as the microvessel density (MVD) of the tumor. The mean MVD was 26.2 ± 13.0 (range 6–68), and it was considered as high (n = 24; 40%), moderate (n = 19; 31.7%) and low (n = 17; 28.3%) when the MVD was >30, between 15–30 and <15, respectively. Statistical analysis included Mann-Whitney, Kruskal-Wallis and Spearman rank correlation tests. The Kaplan-Meier method was used to evaluate the difference between angiogenesis and survival. Multivariate analysis with the Cox regression model was used in MVD values and different clinicopathological parameters. There was positive correlation between MVD increase and surgicopathological stage (p < 0.05). A significant difference was seen between MVD increase and lymph node metastasis (p < 0.05). There were no differences between MVD and age, histological type, grade and lymphovascular invasion. MVD did not change in association with myometrial invasion depth. There was a significant difference in means of survival between the low and high MVD groups (p = 0.01). However, MVD was not an independent prognostic factor in multivariate analysis. Increased angiogenesis was found to be associated with advanced stage and decreased survival in endometrial carcinoma.

Hairy cell leukemia presenting with Guillain-Barre syndrome.

Hairy cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder, which mainly infiltrates the bone marrow and the spleen, resulting in peripheral cytopenias and splenomagaly [1]. Unusual complications including autoimmune phenomena have been described in HCL [2 – 4]. Of these, to the best of our knowledge, Guillain-Barre syndrome (GBS) was reported only in two cases so far [5,6]. Here, we describe a HCL patient who presented with GBS at the time of diagnosis. A 61-year-old previously healthy male was referred to our department complaining of weight loss, night sweats, and pain, weakness and parasthesia progressing from distal to proximal limb muscles for the last 3 weeks. There was no preceding history of viral illness or vaccination or any medication. His physical examination revealed pale appearance, hepatomegaly (3 cm) and splenomegaly (3 cm). Precise neurological examination demonstrated second motor neuron type tetraparesis prominent in the lower extremities (20% muscle strength in lower, 80% in the upper extremities) with hypoactive deep tendon reflexes and loss of vibration sense. Blood picture showed Hb 10.9 g/dl, MCV 96 fl, WBC 10.66 10 l with 44% lymphocytes, 37% hairy cells, 17% PNL, and 2% band leukocyte differentiation, and a platelet count of 2126 10 l. Erythrocyte sedimentation rate was elevated (130 mm/h). Biochemistry tests were normal except for alkaline phosphatase. Serum cobalamin level was found in normal limits. Cytomorphological examination of the bone marrow demonstrated a normocellular marrow with hairy cells infiltration. Flow cytometry of the bone marrow cells revealed positivity for CD19 (64%), CD20 (96.1%), CD11c (98.8%), CD25 (99.1%), CD22 (98.9%), and CD103 (29.3%) and negativity for CD23 (8.5%) and CD5 (3.4%). Histopathological examination of the bone marrow established the diagnosis of HCL (Figure 1). Then, the patient was referred to the Neurology department for consultation. Whole spine magnetic resonance imaging was normal. Lumbar puncture was performed. Protein content of cerebrospinal fluid (CSF) was 201 mg/dl and CSF was acellular. Electroneuromyography (ENMG) was consistent with sensorymotor demyelinating polyneuropathy. The patient was diagnosed as GBS with albuminocytologic dissociation of CSF and ENMG findings reflecting demyelination in both sensory and motor nerves. He was treated with

Extramedullary Plasmacytoma Involving the Abdominal Vessels and Pancreas

To the Editor: We read with great interest the article by Attwell and colleagues [1] in a recent issue of Digestive Diseases and Sciences that described a case of IgA multiple myeloma (MM) involving two unusual extramedullary sites: the porta hepatis and peritoneum. The involvement of abdominal vessels and pancreas by plasma cell neoplasms is very rare and usually diagnosed at autopsy [1–3]. We would like to describe and share our experience in a patient with known MM who developed plasmacytoma on the chest wall and in the abdomen involving the abdominal vessels and pancreas, without concurrent relapse of the disease, and to add some points concerning the treatment of extramedullary plasmacytomas (EMP). A 64-year-old-man was diagnosed to have stage II MM of the IgA(λ) subtype in 2001. He was given a chemotherapy regimen with six courses of melphalan and prednisolone and achieved a plateau phase. In 2002, at the sixth month of the

Pulmonary involvement in a patient with dyskeratosis congenita.

Dyskeratosis congenita (DC) is an unusual familial disorder characterized by atrophy and pigmentation of the skin, nail dystrophy, leukoplakia, bone marrow failure and a predisposition to malignancy. A variety of non-cutaneous (dental, pulmonary, gastrointestinal, neurologic, genitourinary, ophthalmic and skeletal) abnormalities have also been reported. 1 The X-linked recessive and autosomal recessive forms of the disease are recognized. 2,3 Clinical manifestations of DC often appear during childhood. The reticulated skin pigmentation and nail changes typically appear first, usually by the age of 10 years. Mucosal leucoplakia appear later and by the midteens, the serious complications of bone marrow failure and malignancy develop. 1 Pulmonary manifestations have rarely been reported and are often not well documented. Herein, we report on a case with DC and chronic respiratory tract involvement.