Touch imprint cytological diagnosis of nodal Langerhans cell histiocytosis.

Touch imprint cytological diagnosis of nodal Langerhans cell histiocytosis. Langerhans cell histiocytosis (LCH) is a rare neoplasm of the mononuclear phagocytic immunoregulatory system of unknown aetiology. Nodal involvement is uncommon. Cytological findings have seldom been described. A case study of LCH, arising in a submandibular node of a 42-year-old female, is reported. Fine needle aspiration smears were highly cellular and composed of a mixed cell population including eosinophils, lymphocytes, neutrophils, and macrophages. Imprint slides from the surgical specimen of the excised node exhibited Langerhans cells with nuclear grooves, leading to a diagnosis suggestive of LCH. Immunohistochemical staining of the node sections with CD1a and S-100 confirmed this diagnosis. In conclusion, cytology may favorably contribute to the diagnosis of LCH.

Accessory parotid gland carcinoma ex pleomorphic adenoma. Case study diagnosed by fine needle aspiration.

OBJECTIVE: The accessory parotid gland is salivary tissue separated from the main parotid gland and lying on masseter muscle. It has secondary duct emptying into the Stensen's duct. The accessory parotid gland exists in 21-61% of individuals. However, the appearance of an accessory parotid tumor is rare, with a reported frequency of 1-7.7% of all parotid gland tumors. Carcinoma ex pleomorphic adenoma arises from a pre-existing benign mixed tumor. Most of these tumors will have malignant epithelial component, but not malignant stromal component. Reports of Fine Needle Aspiration Cytological (FNAC) diagnosis of malignant mixed tumor are uncommon and have been limited to cases arising in the parotid. We report a case of carcinoma ex pleomorphic adenoma of the accessory lobe of the parotid, and address the cytopathology features and pitfalls of this condition. CASE: A 73 aged female presented with a right nontender midcheek mass. The lesion had been present 18 months, with a recent increase in size. FNA was performed and the smears demonstrated features indicative of pleomorphic adenoma admixed with findings indicative of a poorly differentiated carcinoma. CONCLUSION: FNAC can accurately diagnose carcinoma ex pleomorphic adenoma when strongly fixed requirements are implemented.

Fibroadenoma masquerading carcinoma on fine-needle aspiration of the breast.

OBJECTIVE: Benign and malignant lesions of the breast may have similar appearances on fine-needle aspiration cytology. We report a case of fibroadenoma that was diagnosed as carcinoma by cytology. CASE STUDY: Breast fine-needle aspiration biopsy was highly cellular and composed of bland-appearing spindle/columnar cells that could represent either epithelial or stromal cells; the case was reported as positive and the patient had subsequent excisional biopsy taken. RESULTS: On microscopic examination, smears were hypercellular and had many single cells and clusters of columnar/ elongate cells No obvious bipolar cells of myoepithelial origin were seen. Significant atypia was noted. Immunocytochemistry for smooth muscle actin was not performed due to insufficient material. CONCLUSIONS: Some cases of fibroadenoma and carcinoma can be very difficult to distinguish on fine needle aspiration cytology smears. Immunocytochemistry may be of help if sufficient material is provided. To avoid false positive diagnosis on cytology, it is best to report such a case as intermediate (atypical/suspicious) with final interpretation pending excisional biopsy.

Endometriosis involving the rectus abdominis muscle and subcutaneous tissues: fine needle aspiration appearances.

OBJECTIVE: Endometriosis is defined as functioning endometrial tissue outside the uterine cavity. It occurs in up to 15% of menstruating females and in most cases is located within the pelvis. Endometrial implants, however have been described in soft tissues, particularly in the skin and subjacent tissues of surgical scars, and diagnosis might be problematic. CASE STUDY: A 32 aged female presented with a suprapubic abdominal mass, which appeared suddenly after exercise. Fine needle aspiration was performed. RESULTS: Epithelial sheets were shown in direct aspirates. No evident endometrial stromal cells were seen. CD10 immunostaining in additional cell block preparations using a commercial antibody gave positive results. The cell pattern and immunocytochemical profile suggested a cytodiagnosis of endometriosis. The patient was administered with leuprolide acetate. She experienced adverse effects related to estrogen deficiency. Medical treatment was discontinued and the patient underwent surgical excision. Histological sections revealed endometrial glands surrounded by stroma and embedded in fibrous connective tissue. CONCLUSION: With optimal preparations a confident cytological diagnosis of endometriosis may be established easily, allowing correct treatment of the disease and, in selected cases, planning of preoperative pharmacologic therapy.

Normal development of fetal hepatic haematopoiesis during the second trimester of gestation is upregulated by fibronectin expression in the stromal cells of the portal triads.

OBJECTIVE: in midtrimester fetuses the principal site of hematopoiesis is the liver. In hematopoietic organs, stromal cells such as fibroblasts, epithelial cells, and macrophage-like cells develop networks to maintain hematopoiesis, i.e. hematopoietic stem cell self-renewal, proliferation, and growth, by interaction with hematopoietic progenitor cells. ECM glycoproteins produced by the stromal cells are known to play a critical role in the regulation of cell growth and differentiation. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about fetal hepatic stromal cell activity and stromal extracellular matrix protein-fibronectin, on fetal hepatic haematopoiesis. The binding of late stage erythroid cells to fibronectin has been well characterized and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to determine the role of fibronectin in fetal hepatic hematopoietic proliferation and differentiation in different stages of development. MATERIAL AND METHOD: we examined and compared the immunohistochemical expression of fibronectin in the hepatic stromal portal fields in the 1st, 2nd, and 3rd trimester of gestation respectively, in relation to the appearance of CD34 progenitor hematopoietic, stromal progenitor and vascular endothelial positive cells. RESULTS: our results demonstrated a quantitative difference in the second trimester of gestation concerning the expression of fibronectin in the connective tissue stroma of the hepatic portal fields over the equivalent expression of the protein in the first (p < 0.0001, t-test) and third trimester (p < 0.0001, t-test). Similar changes in the above period were found concerning the expression of CD34 during the second trimester of gestation, over the first (p < 0.0001, t-test) and third trimesters (p < 0.0001, t-test), suggesting a direct involvement of fibronectin in the sustaining of hematopoietic activity. CONCLUSIONS: our data provide evidence that an ECM glycoprotein component, fibronectin, plays a relevant role in hematopoiesis through interaction between stromal cells and hematopoietic progenitor cells.

Induction of hepatic haematopoiesis with fibronectin expression by EMT stromal cells during the second trimester of development.

In an initial period of vertebrate phylogeny (bone marrow-less vertebrates), lymphohaematopoiesis takes place in numerous organs containing a suitable microenvironment. Among other organs (i.e., gonads, kidney and spleen), the liver is apparently the most appropriate site for homing and differentiation of haematopoietic cell precursors. Interaction between haematopoietic cells and stromal cells is important for regulation of haematopoiesis. Numerous soluble and membrane-bound factors directly regulating haematopoiesis have been documented, but little is known about the effect of the foetal hepatic epithelial-to-mesenchymal transition (EMT) stromal cells' activity and their product-fibronectin, on foetal hepatic haematopoiesis. The binding of late-stage erythroid cells to FN has been well characterised and is believed to be critical for the terminal stages of erythroid differentiation. The intention of this article is to provide a quantitative overview of FN, produced by hepatic EMT stromal cells, in foetal hepatic haematopoiesis during the first and second trimester of development. Paraffin-embedded specimens from the liver of 30 human embryos in the first and second trimesters of gestation were investigated by conventional histology and immunohistology for the presence of FN and specific haematopoietic cell types. The staining intensity, and localisation of FN and haematopoietic markers in sequential sections were examined. Furthermore, double immunohistochemical staining was performed to assess simultaneous detection of FN and haematopoietic markers. FN was expressed in the EMT stromal cells of the hepatic portal triads more strongly during the second trimester than the first. Furthermore, an intense immunostaining for haematopoietic lineages, and especially for erythropoiesis, was observed in the second trimester compared to the first. The results of the double immunostaining disclosed an intimate co-expression of the FN and CD haematopoietic markers. Foetal hepatic EMT stromal cells provide a unique microenvironment that supports the emergence, expansion and maintenance of human foetal haematopoietic development during the mid-gestational stage. FN produced by the EMT stromal cells follows a time course parallel to that of haematopoiesis. We suggest that in foetal liver, phenotypic modifications of EMT stromal cells expressing FN concerning the cell adhesion capacity of the protein are associated with proliferation and differentiation of specific haematopoietic cell lineages during the second trimester of gestation, probably reflecting the increasing demand of the growing foetus for mature erythroid and myeloid cells.

Primary MALT lymphomas of the stomach: a pathological study of 18 cases.

AIM: It is doubtful that whoever is suffering from gastric malt lymphoma will escape from the disease, if treated with medication against helicobacter pylori. MATERIAL AND METHODS: A cohort of 18 patients was analysed. Ten hosts had primary gastric malt lymphoma and were treated with gastric resection as the initial therapy. Eight hosts received antibiotics against Helicobacter pylori as the initial treatment. In all 18 patients Helicobacter pylori status, endoscopic findings and pathology features were evaluated. Immunohistochemistry was performed to assess the bcl-2 and p53 status. RESULTS: Patients with low grade malt lymphoma: a) were Helicobacter pylori positive (5 of 5); b) had a superficial lesion (5 of 5); c) had no lymph node involvement (5 of 5); and d) were downstaged by comparison to patients with high grade tumor. Bcl-2 was positive in 4 of 5 low grade tumors, and p53 was positive in 12 of 13 high grade ones. Investigation of patients with 5-year follow up (n = 18) revealed that all but one low-grade tumors remained superficial with no progression. These tumors were bcl-2+/p53-, and the one with a bcl-2+/p53+ immunophenotype progressed to an ulcerated low-grade tumor after disappearance of Helicobacter pylori. Complete regression was found in 6 of 8 patients from the non surgically treated group (n = 8) after Helicobacter pylori eradication. These tumors were superficial/low grade/node negative/bcl-2+/p53 inconclusive (n = 2), superficial/low grade/node negative/bcl-2+/p53- (n = 2), and ulcerative/high grade/node negative/bcl-2+/p53- (n = 2). The two persistent tumors were ulcerative/high grade/node negative/bcl-2+/p53+. CONCLUSION: Gastric malt lymphoma Helicobacter pylori+/superficial/low grade/bcl-2+/p53- will disappear after Helicobacter pylori eradication.

Concurrent low grade B-cell non-Hodgkin's lymphoma of MALT type arising in the large intestine, small intestine and stomach.

Low-grade non-Hodgkin's lymphomas (NHL) of mucosa associated lymphoid tissue (MALT) are indolent neoplasms that, although tending to remain localized for many years, may spread to other mucosal sites. Despite increasing identification of concurrent gastric and intestinal lymphoma of MALT type, the clonal relationship between the tumors and their sequential development are poorly understood. It is also unknown whether the development of these concurrent tumors is closely associated with direct antigen stimulation, which is thought to play an important role in the clonal expansion of low grade MALT lymphomas. The most important function of B-cells is production of specific antibodies. This is largely achieved during B-cell development by recombination of the Ig heavy chain variable (V), diversity (D), and joining (J) segments and hypermutation of the rearranged gene. The rearranged Ig genes of a mature B-cell record much of its evolution history. We report a case of synchronous development of intestinal and gastric low grade MALT lymphomas in a 70 years old female and discuss their possible clonal relationship and sequential appearance.

A stromal myoid cell line provokes thymic T-cell immigration at the second and third gestational trimesters.

UNLABELLED: Once lymphoid precursors enter the thymus form the blood stream, they come into contact with thymic stromal cells that guide their maturation into functionally competent T cells. Thymic myoid cells are one such cell type. They have been described as a regular constituent of the thymus of embryonic and young vertebrates and express muscle proteins including myosin, desmin, acetylcholine receptor (AChR), C-protein, MyoD, troponin T, rapsyn, and utrophin. It has been emphasized recently that the thymic myoid cells play an important role in the protection of thymocytes from apoptosis, and in the process of T-cell differentiation and maturation. AIM: To provide a quantitative estimation of thymic myoid cells and T-cell population in different stages of development. A probable interaction between these two populations could explain an additional mechanism to the active T-cell migration from the thymus that is a direct contact to a specific myoid cell line. MATERIALS AND METHODS: Paraffin-embedded specimens from the thymus of forty five human embryos at the first, second and third trimester of gestation respectively, were investigated by conventional histology, and immunohistology for the presence in the stroma of the thymic medulla, of myosin in the myoid cells, and UCHL1 (pan T-cell) antigen in the medullary thymocytes. RESULTS: Our results demonstrated a quantitative difference in the second and third trimester of development concerning the expression of myosin in the stromal myoid cells of the thymic medulla over the equivalent expression of the protein in the first trimester. Similar changes in the above periods were found concerning the population of medullary thymocytes expressing UCHL1 antigen. CONCLUSIONS: Our results indicate that: (1) Thymic myoid cells play an important role in the thymic microenvironment as they are well conserved throughout species evolution. (2) The increased population of myoid cells in the medullary area during mid and late gestational age, in comparison with first trimester, probably reflects the increased demand of the growing fetus for mature T lymphocytes. Contractions of myoid cells mediated by their cytoplasmic structural proteins, including myosin which is well preserved during development, might aid the movement of thymocytes expressing UCHL1 antigen, across or out of the gland, suggesting a potential involvement of myoid cells in the thymic function. Further studies on larger series are needed to corroborate this.

Loss of chromosome 1 in myxopapillary ependymoma suggests a region out of chromosome 22 as critical for tumour biology: a FISH analysis of four cases on touch imprint smears.

OBJECTIVE: Ependymomas are glial tumours. They constitute approximately 5-10% of intracranial tumours and are tumours which can recur. Predictive factors of outcome in ependymomas are not well established. Karyotypic studies are relatively scarce and loss of chromosome 22 has been described to correlate with recurrence. We are unaware of any reports involving chromosome 1 aberrations in the malignant progression of ependymomas. METHODS: Cytogenetic analysis of four myxopapillary ependymomas was performed using double target fluorescent in situ hybridization (FISH), focusing on chromosomes 1 and 22. RESULTS: One patient's tumour had recurred. FISH was performed on 500 nuclei/tumours. All four cases showed a loss of chromosome 22q while only one showed an additional loss of chromosome 1p, and this was the one that recurred. CONCLUSIONS: We support the presence of a tumour suppressor gene on 1p associated with relapse in myxopapillary ependymomas and suggest that status of chromosome 1p by FISH may indicate a high-risk group of patients harbouring this tumour. More studies of this type are needed towards this direction as our results refer to a minimal number of individuals analysed.

Distribution of somatostatin in pancreatic ductal adenocarcinoma remodels the normal pattern of the protein during foetal pancreatic development: an immunohistochemical analysis.

AIM: To determine the immunoreactivity of somatostatin during the development of the human fetal pancreas and pancreatic ductal adenocarcinoma, given that, somatostatin-positive cells were demonstrated either into its embryonic anlage or into pancreatic cancer. METHODS: Tissue sections from 15 pancreatic fetal specimens, and an equal number of ductal adenocarcinoma specimens were assessed. RESULTS: The density of positive cells in the primitive exocrine ductal epithelium and endocrine epithelium was significantly different from the relevant density in the neoplastic pancreatic tissue of mixed (ductal-endocrine) and pure ductal type (P1=0.021 P2=0.001, P3<0.0001, P4=0.003 respectively). The above values were estimated from the 8th to 10th week. There was no significant difference in the density of positive cells in the mantle zone of the islets from the 13th to the 24th week, and the neoplastic tissue of mixed (P5=0.16) and pure ductal type (P6=0.65). CONCLUSION: The immunostaining for somatostatin identifies a subgroup of pancreatic ductal adenocarcinomas with a neuroendocrine component, (initially considered as pure ductal tumors), and mixed ductal and neuroendocrine tumors. This pattern of expression in neoplasms recapitulates the normal pattern during the embryonal development of the organ, raising the question of therapeutic efficacy of somatostatin and analogues as monotherapy in pancreatic cancer management.

Contribution of combined colposcopy and cytology in cervical pathology.

AIM: The regular Papanicolaou (Pap) smear is the cornerstone of women's preventive healthcare. The introduction of the regular Pap smear as a screening tool for cervical cancer has markedly decreased the number of deaths from cervical cancer. During the past decade, however, the rate of death from cervical cancer has remained relatively static. This screening method is known to have a high percentage of false negative results. To improve the detection of cervical lesions using the Pap smear in screening, a number of adjunct procedures have been developed. The purpose of this study is to evaluate the utility of a magnified chemoluminescent screening examination (Colposcopy) combined with the Pap smear in detecting cervical abnormalities. METHODS: We investigated a cohort of 58 subjects who have been forwarded for colposcopic evaluation due to referral cytology suggestive of persistent inflammatory process not otherwise specified, and cervical intraepithelial or invasive neoplasia, in Chania Colposcopic clinic. RESULTS: The higher the lesion detected by cytology, the more severe the corresponding colposcopic impression viewed. CONCLUSION: The data presented here are in harmony with previous reports and share our experience in a Regional Community Hospital Colposcopy Clinic. An integrated cytology-colposcopy program facilitates the assessment and identification of women harboring cervical pathological conditions.

Ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and synchronous cervical squamous carcinoma.

Solid mural nodule within a mucinous cystic ovarian tumor occurs more often than generally presumed. One especially interesting case involving coincidental cervical carcinoma is presented. A 38-year-old woman underwent exploratory laparotomy for a right ovarian tumor. After ovarian malignancy had been diagnosed from frozen section, the bilateral salpingo-oophorectomy and hysterectomy was performed. The tumor had a unilocular cystic cavity and a mural nodule. The nodule showed undifferentiated carcinomatous features. The immunohistochemical examination revealed atypical cells in the nodule which were positive for cytokeratin, CEA, and vimentine, establishing its anaplastic nature. A synchronous cervical invasive squamous carcinoma was documented. The patient was treated with chemotherapy and radiotherapy. Currently, at 15 postoperative months, she is well and free of disease. The occurrence of ovarian mucinous cystadenocarcinoma with mural nodule of anaplastic carcinoma and cervical squamous cell carcinoma is evidently very uncommon, because we have not found a similar case in the literature.

Local immune response in serous papillary carcinoma of the endometrium.

OBJECTIVE: Serous papillary carcinomas of the endometrium are aggressive tumors that tend to permeate, in a very extensive fashion, to uterine and adnexal lymphatic and vascular channels at an early stage in their evolution, and are associated with a particularly gloomy prognosis. It is generally thought that even tumors apparently limited to the endometrium or confined to an endometrial polyp have a poor outcome. Our study points towards the value of HLA-DR antigen in the outcome of serous papillary endometrial cancer. Our aim was to assess the HLA-DR expression in inactive, endometrial intraepithelial carcinoma (EIC), and invasive serous carcinoma curretage specimens from the endometrial cavity, suggesting a role in immune response to keep tumor proliferation in check. STUDY DESIGN: Thirty-one cases of inactive endometrium, twelve cases of EIC, and thirty-nine cases of serous papillary invasive carcinoma curettings were evaluated for the detection of HLA-DR monoclonal antigen. T helper (TH) marker (CD4) in the tumor stroma of the relevant cases was also studied, given that it is now known that the dependence of immune responsiveness on the class II antigens reflects the central role of these molecules in presenting antigen to TH cells. RESULTS: HLA-DR was expressed in 20 of 31 inactive endometrium (64.5%), 4 of 12 in EIC (33.3%), and in 10 of 39 serous papillary invasive carcinomas (25.6%). CD4 was expressed in 9 of 31 inactive endometrium (29%), 5 of 12 in EIC (42%), and in 26 of 39 serous papillary invasive carcinomas (67%). CONCLUSIONS: The results showed decreased expression of HLA-DR and increased expression of CD4 as the lesion progressed to malignancy. The aberrant expression of HLA-DR by epithelial cells of inactive endometrium, of EIC and of serous papillary invasive carcinomas agrees with the hypothesis of the inactive endometrium - carcinoma in situ sequence as the usual route for the development of serous papillary invasive carcinoma. The immune attract mechanism by low HLA-DR signaling seems to be of minor importance in the malignant and metastatic potential of the serous papillary endometrial tumours.

Primary gastric Hodgkin's lymphoma: a case report and review of the literature.

Primary gastric Hodgkin's lymphoma is a rarely encountered lesion. Most cases are observed in the course of systemic disease. Other cases have been reclassified in retrospective studies as non-Hodgkin's lymphomas, after the employment of immunohistochemistry. Some Hodgkin's lymphomas may masquerade non-Hodgkin's lymphomas, and vice versa. Therefore, an accurate diagnosis is important, as treatment and outcome differ significantly for these entities. We report a case of primary Hodgkin's lymphoma arising in the stomach of a 46-year-old male, and discuss the diagnostic approach as well as the differentials of Hodgkin's disease in this anatomic site.

Bilateral metastatic rhabdomyosarcoma to the breast in an adolescent female: touch imprint cytology and implication of MyoD1 nuclear antigen.

BACKGROUND: Rhabdomyosarcoma accounts for approximately 4% of all childhood malignancies. Breast metastases from rhabdomyosarcoma are uncommon with an incidence of 6%. CASE REPORT: We present a patient who developed bilateral mammary metastases from rhabdomyosarcoma arising in the right lower extremity. An 11-year-old female with a 20-month history of rhabdomyosarcoma was referred to our department because of bilateral breast enlargement. A needle core biopsy was performed and touch imprint slides were obtained. Cytology determined the masses to be metastases of rhabdomyosarcoma. MyoD1 immunostain and RT-PCR analysis confirmed the diagnosis. CONCLUSIONS: Cytomorphology with ancillary methods is essential in the diagnosis of metastatic breast deposits in order to avoid unnecessary mastectomy and to employ systemic treatment.

Inflammatory pseudotumor of the spleen.

We report a case of a patient with inflammatory pseudotumor (IPT) of the spleen. IPTs can appear at many sites and represent rear lesions of uncertain etiopathogenesis. Usually they present as mass lesions, so the clinical and radiologic features often suggest malignancy. However, the microscopic findings are quite characteristic, and the diagnosis can be made readily by identifying the reactive nature of the cells. Diagnostic problems can arise when these lesions occur in lymphoid organs or the spleen.

Diffuse large B-cell lymphoma arising from a multicentric mixed variant of Castleman's disease.

This case report describes a patient with multicentric mixed type Castleman's disease and concomitant non-Hodgkin's lymphoma of diffuse large B cell type in the neck. Multicentric CD is a systemic illness with disseminated lymphadenopathy; its aggressive and usually fatal course is associated with infectious complications and risk for malignant tumors, such as lymphoma or Kaposi sarcoma.