Szépe P

Salivary Duct Carcinoma - A Highly Aggressive Salivary Gland Tumor with HER-2/neu Oncoprotein Overexpression

Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.

Cutaneous lymphoid hyperplasia and other lymphoid infiltrates of the breast nipple: a retrospective clinicopathologic study of fifty-six patients.

This study characterizes the clinicopathological spectrum of lymphoproliferations involving the breast nipple and/or areola. Morphologic, immunohistochemical, molecular-genetic, and clinical features of 58 specimens from 56 patients were analyzed. They were re-diagnosed as cutaneous lymphoid hyperplasia (CLH, n = 44); other benign lymphoid infiltrates (OBLI, n = 8); peripheral T-cell lymphoma, not otherwise specified (n = 1); cases with overlapping features of CLH and B-cell lymphoma (n = 3), one of them composed of spindle cells. Cutaneous lymphoid hyperplasia infiltrates were dense, composed mainly of B cells forming follicles with germinal centers (GC). Cutaneous lymphoid hyperplasia frequently showed features suggesting a malignancy as coalescing follicles with non-polarized germinal centers lacking mantle zones, and smudged infiltrates of lymphoid cells spreading into collagen (often as “Indian files”), smooth muscle, vessel walls, and nerve sheaths. Only two cutaneous lymphoid hyperplasias recurred; otherwise all patients are without disease (mean follow-up 62 months). Monoclonal rearrangement of immunoglobulin heavy chain gene was detected in five, and of T-cell receptor γ gene in two cutaneous lymphoid hyperplasias using polymerase chain reaction (PCR), but the patients fared well too. In 47% of cases Borrelia burgdorferi was detected by polymerase chain reaction and/or serology, of which one was monoclonal. We conclude that cutaneous lymphoid hyperplasia is the most common lymphoproliferation of the breast nipple, rarely recognized clinically, and often overdiagnosed histologically as lymphoma.

Spiradenocylindroma-Like Basaloid Carcinoma of the Anus and Rectum : Case Report, Including HPV Studies and Analysis of the CYLD Gene Mutations

The authors report a case of basaloid carcinoma involving the anus and rectum of a 57-year-old woman. Microscopically, the tumor showed unusual morphologic features strongly resembling a spiradenocylindroma because it consisted, in most parts, of basaloid cell nodules arranged in a jigsaw-puzzle fashion containing or surrounded by eosinophilic basal membrane material; in addition, there were intratumoral lymphocytes. The overlying squamous epithelium manifested dysplastic changes compatible with in situ squamous carcinoma that gradually became invasive and blended with basaloid cell islands; additionally, there were koilocytes in the squamous epithelium. A molecular biology study identified HPV-16 in the lesional tissue. Analysis of the CYLD gene did not prove any mutation.

Spectrum of mutations in gastrointestinal stromal tumor patients – a population‐based study from Slovakia

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of gastrointestinal tract and are characterized by presence of mutations in tyrosine kinases cKIT (KIT) and PDGFRα (PDGFRA). Mutations identified are highly heterogeneous, but some mutations are associated with specific clinical features of the tumor. Samples from 278 GIST patients collected during the period 2004–2011 were screened for mutations in exons 9, 11, 13, and 17 of KIT and 12, 14 and 18 of PDGFRA. Results of mutation screening were summarized and tested for possible association with clinical parameters of tumors. Mutations were identified in 83.81% of patients. Most frequent mutations were found in KIT exon 11 reaching frequency of 62.95%. Other exons contributed to the mutation pool with frequencies 8.27%, 7.55%, 2.52%, 1.44%, 1.08%, and 0.00%, in decreasing order KIT exon 9, PDGRFA exons 18 and 12, KIT exon 13, PDGFRA exon 14, and KIT exon 17. General linear model analysis showed no effect of any individual analyzed mutation on the phenotypic variables, but we confirmed association between mutations KIT exon 9 p. 503‐504_dup2, and PDGFRA exon 18 p. D842V and intestinal and gastric localization of tumors.

A novel JAK2 exon 12 mutation identified in the retrospective analysis of paraffin-embedded tissues of polycythemia vera patients.

The aim of the study was to screen formalin-fixed, paraffin-embedded tissues of polycythemia vera patients for the presence of JAK2V617F and JAK2 exon 12 mutations. Of 64 cases, 60 were positive for JAK2V617F mutation using allele-specific polymerase chain reaction (PCR). Using modified allele-specific PCR, samples of 4 JAK2V617F-negative patients were analyzed for the presence of JAK2 exon 12 mutations. In one case, we found a PCR product matching with allele-specific primer, which was designed to detect the N542-E543del mutation. Surprisingly, in the result sequence we have detected another recently described mutation, R541-E543delinsK. In the other 3 JAK2V617F-negative patients, allele-specific PCR for the detection of JAK2 exon 12 mutations did not yield any product. However, in 1 case, the sequencing of JAK2 exon 12 PCR product revealed a novel mutation, H538-K539delinsF. We confirmed that paraffin-embedded tissues represent a valuable source of DNA, which can be used in diagnostics of both JAK2 exon 12 and exon 14 mutations and we described 1 novel JAK2 exon 12 mutation.

DNA methylation and detection of cervical cancer and precancerous lesions using molecular methods

Cervical cancer is the third most common cancer disease affecting the female population, and a key factor in the development of the disease is the human papillomavirus infection (HPV). The disease is also impacted by epigenetic changes such as DNA methylation, which causes activation or exclusion of certain genes. The aim of our review is to summarize and compare the most common molecular methods for detection of methylated promoter regions in biomarkers occurring in cervical carcinoma and also show the importance of connections of HR-HPV testing with methylation analysis in patients with cervical intraepithelial neoplasia. Insight into genetic and epigenetic alterations associated with cervical cancer development can offer opportunities for the molecular biomarkers that can be useful for screening, diagnosis, and also as new ways of treatment of cervical cancer precursor lesions.

Syringocystadenocarcinoma Papilliferum In Situ-Like Changes in Extramammary Paget Disease: A Report of 11 Cases

Abstract:The authors report 11 cases of extramammary Paget disease (EMPD), all of which also demonstrated a combination of histological changes highly reminiscent of syringocystadenocarcinoma papilliferum in situ. In addition to the classical features of EMPD, characterized by the intraepidermal spread of individually dispersed neoplastic cells with ample cytoplasm, many of which contained mucin, there were areas of acanthosis with the substitution of spinous layer keratinocytes by neoplastic cells, whereas the native basal cell layer was intact. In addition to acanthosis (and sometimes papillomatosis), the dermal papillae showed a prominent infiltrate of plasma cells, completing the resemblance to syringocystadenocarcinoma papilliferum in situ; this similarity was further enhanced in 2 cases, which showed conspicuous gland formation. One additional case showed multifocal dermal proliferations compatible with eccrine syringofibroadenoma (syringofibroadenomatous hyperplasia). The changes described herein seem to be relatively rare in EMPD, and they can represent a diagnostic pitfall, as evidenced by 2 cases that were originally misinterpreted as syringocystadenocarcinoma papilliferum in situ. Clinically, these microscopic changes sometimes corresponded to nodular lesions, which were specifically noted to have a papillated erosive surface.

A case of systemic mastocytosis--an ultrastructural and immunohistochemical study of the dermal mast cells in relation to activation of the epidermal melanin unit.

To the Editor: Mastocytosis is a disease characterized by an abnormal increase in mast cells and their abnormal accumulation in tissues [1,2]; it has been associated with haematologic and lymphoprolipherative disorders [3-61. We present a rare case of systemic mastocytosis with ‘atypical dermal mast cells’ infiltrates and activation of the epidermal melanin unit. A 1-month-old boy with disseminated yellowbronze confluent skin lesions, small papules with vesiculation and erythematous rash was presented (Fig. 1). The patient had noteworthy systemic intermittent flushing and fever, diarrhea and attacks of bronchospasmus with hepatosplenomegaly, generalized (also mesentheric) lymphadenopathy diagnosed by abdominal ultrasonography . Routine laboratory evaluation revealed anaemia, mild macrocytosis, anisocytosis with multiple spherocyte cells, anisochromia, polychromasia, reticulocytosis, lymphocytosis and thrombocytopenia, with some pathological values of haematologic coagglutinating factors (Table 1). Other haematologic parameters included absolute eosinophil count and haematologic coagglutinating factors. Bone marrow (sternal puncture) was slightly hypercellular, with M E ratio (myelopoietiderythropoietic cells) of 1-3.4:l-1.5; 26% of the mast cell findings were in confluent clusters within the marrow aspirates. As a result of clemastine treatment (0.4 mg/day) in combination with ketotifen (1 .O mg/day), antagonists of H2 receptors and with diet were without therapeutic effect, prednisone treatment (1.5 mg/kg of body weight) was started. After 1 year of consistent treatFig. 1 . A month-old boy with systemic mastocytosis, multiple confluent vesiculation.

Uncommon leukemic case of anaplastic large cell lymphoma diagnosed through a typical chromosomal abnormality t(2;5) with a null phenotype and aberrant expression of NG2 and CD13.

Anaplastic large cell lymphoma represents approximately 10-15 % of pediatric non-Hodgkin lymphomas. Leukemic presentation is very rare, and in particular, the null phenotype ALCL without typical anaplastic morphology together with aberrant expression of CD13 and/or CD11b represents a diagnostic challenge. We report a case of a 9 year-old boy with leukemic presentation of ALCL with the typical translocation t(2;5)(p23;q35); in this patient, the only positive antigens identified by immunophenotyping were CD13, NG2 HLA-DR, and CD38. To our knowledge, aberrant expression of NG2 has never been reported in ALCL cases (Tab. 1, Fig. 6, Ref. 20).

Lymphoepithelial lesions formed by lymphoma cell infiltration of the solid cell nests of the thyroid gland

Sir: Although the thyroid gland is not strictly a mucosal organ, it is derived from the foregut, and the lymphoid tissue that accumulates in the thyroid in Hashimoto’s thyroiditis shares features with mucosa associated lymphoid tissue (MALT). In agreement with this, lymphomas arising in Hashimoto’s thyroiditis have, as a rule, the properties of MALT lymphomas. These thyroid gland lymphomas produce lymphoepithelial lesions, which consist of thyroid follicles permeated by small to medium-sized lymphocytes. We describe a different type of lymphoepithelial lesion formed by lymphoma cell infiltration of the solid cell nests in a tumour of the left lobe of the thyroid gland in a 67-year-old man. Histologically, a part of the thyroid parenchyma not involved by lymphoma showed diffuse oxyphylic change, with nodules of lymphoid infiltration typical of Hashimoto’s thyroiditis. Another portion of the thyroid gland was involved by lymphoma and showed thyroid parenchyma infiltrated by small to medium sized cells with centrocyte-like features, which immunohistochemically revealed monoclonal kappa light chain restriction of cytoplasmic immunoglobulins. A further feature was the presence of numerous solid cell nests composed of polygonal or elongated cells with eosinophilic cytoplasm showing an epidermoid-like appearance, oval nuclei with one or two nucleoli, dispersed within the lymphoid aggregates of the lymphoma and Hashimoto’s thyroiditis. Immunohistochemically, the solid cell nests strongly expressed carcinoembryonic antigen but were negative for thyroglobulin and calcitonin. These nests were infiltrated by small to medium sized cell lymphocytes with centrocyte-like features (Figures 1 & 2). Morphologically, these lymphoid cells were often surrounded by a clear halo, a feature often seen in the lymphoepithelial lesions in the stomach. Imunohistochemically, they were L26 and LCA positive and CD3 negative. The infiltration varied from a mild degree (Figure 1) to a severe one (Figure 2). Mildly infiltrated solid cell nests were usually located within the thyroid parenchyma, with Hashimoto’s thyroiditis changes close to the margin of thyroid gland infiltrated by the low-grade MALT lymphoma. The ultimobranchial contribution to the thyroid gland is known to derive from the fourth and fifth branchial pouches. It has a wide developmental potential, which may have an implication for thyroid neoplasia. It is presently accepted by some authors that the solid cell nests of the thyroid represent remnants of the ultimobranchial body. The ability of the cell nests to form lymphoepithelial lesions is not surprising because of the endodermal origin of ultimobranchial bodies, from which the solid cell nests arise. The close relationship of the origin of the ultimobranchial bodies to the thymic anlage (thymus IV) is well known, and the thymus is another organ where MALT lymphoma may, rarely, arise. The solid cell nests can also differentiate into salivary gland tissue and it is also well known that virtually all lymphomas arising in Sjögren’s syndrome in the salivary Histopathology 1996, 28, 569–571