[Joint swelling, reversible arm paresis, and elevated serum IgG4 in a 55-year-old man]. / Gelenkschwellungen, reversible Armparese und erhöhtes Serum-IgG4 bei einem 55-jährigen Patienten.

Only described in the last 10 years, IgG4-related disease is a fibroinflammatory disorder characterized by tumorous lesions with dense lymphoplasmacytic infiltration by IgG4-positive plasma cells and often elevated concentration of serum IgG4. In this paper, we present a male patient with this disease involving the lymph nodes and possibly the joints and kidneys. Infiltration of lymph node tissue with IgG4-positive plasma cells was demonstrated. The general condition of the patient improved considerably by immunosuppressive therapy.

Testosterone synthesis in patients with 17ß-hydroxysteroid dehydrogenase 3 deficiency.

17ß-hydroxysteroid dehydrogenase 3 (17ß-HSD 3) deficiency is a rare cause of 46,XY disorders of sex development (DSD). At puberty, these patients experience a surge of androstenedione and also testosterone, leading to substantial virilization. The origin of testosterone synthesis in these patients remains elusive. We investigated the expression of the isoenzyme AKR1C3 (17ß-HSD 5) in the testis and patient-derived genital skin fibroblasts (GSF) as well as the ability of GSF to synthesize testosterone. Supernatants of GSF cultures and serum samples of one patient before and after gonadectomy were analyzed by liquid and gas chromatography/mass spectrometry. The androgenic potential of GSF-derived supernatants was also assessed by androgen receptor-mediated transactivation of a reporter gene in transiently transfected Chinese hamster ovary cells. Although AKR1C3 is expressed both in the testes and in GSF, androstenedione is rapidly metabolized and is not synthesized to testosterone. The transactivation potential of GSF supernatants towards the androgen receptor is declining within 48 h. However, under testis-equivalent androstenedione concentration, testosterone can be synthesized in 17ß-HSD 3-negative GSF. After gonadectomy, both androstenedione and testosterone decline rapidly in vivo. In 17ß-HSD 3 deficiency, relevant amounts of testosterone are synthesized most probably through AKR1C3 in the testis and not peripherally in GSF.

Schmincke's Tumor, Carcinoma of the Base of the Tongue c T1-2, cN2c M0 - A Case Report.

BACKGROUND: Lymphoepithelial tumors are the most common carcinomas of the nasopharynx. The non-differentiated tumor, also called Schmincke's tumor, is more prevalent in the African and Chinese population. The incidence of the tumor according to age peaks between 20 and 30 years of age, and after 60 years of age. The tumor is rarely located outside of the nasopharynx. Case Report: This report is about a 73-year-old female patient diagnosed with a tumor of the base of the tongue. The histological result shows a low-grade carcinoma of the squamous epithelium, a lymphoepithelial carcinoma. CONCLUSION: Despite the tumor's rare manifestation outside the nasopharynx, one must also consider the non-differentiated carcinoma of lymphoepithelial matrix. Especially due to the well-known early tumor spreading, cervical lymph node swelling on both sides can be recognized as a possible early symptom. First-line therapy consists of primary radiation of the tumor's primary region and its lymphoid draining channels. Concomitant chemotherapy can be applied. In case of cervical tumor spreading, a neck dissection reduces the risk of local recurrence.

Isolated lympho-histiocytic inflammation of the Gasserian ganglion mimicking trigeminal schwannoma.

UNLABELLED: We present an unusual case of a patient with trigeminal pain and hypesthesia suggesting trigeminal schwannoma, where histology demonstrated an inflammatory lesion of the Gasserian ganglion. CLINICAL PRESENTATION: Patient history and imaging were typical for a trigeminal schwannoma with a dumbbell growth in the middle and posterior fossa. Surgery was performed and resection of a firm mass intermingled with fascicles originating from the ganglion and the mandibular branch was carried out via a subtemporal approach. Histological diagnosis revealed a non-caseating, vaguely granulomatous lymphocyte- and histiocyte-rich inflammation. CONCLUSION: Inflammatory lesions of the Gasserian ganglion are rare but may mimic tumors. Intraoperative biopsies should be taken prior to complete resection to limit neurological deterioration.

[Cancer-to-cancer metastasis: amelanotic melanoma into renal cell carcinoma]. / Karzinom-in-Karzinom-Metastasierung eines amelanotischen Melanoms in ein Nierenzellkarzinom.

HISTORY AND PHYSICAL FINDINGS: A 54-year old man was admitted because of motor aphasia, behavioral changes and weight loss and suffered from a widely disseminated cancer with unknown primary origin (CUP) syndrome. DIAGNOSIS: The autopsy revealed that he was affected by two malignant neoplasms simultaneously: an amelanotic malignant melanoma metastasizing into a localized renal cell carcinoma. CONCLUSION: Cancer-to-cancer metastasis is an exceedingly rare, but well documented phenomenon. This is the third reported case of a malignant melanoma as donor tumor spreading into a renal cell carcinoma. Well-vascularized and slowly growing renal tumors are typical recipients for cancer-to-cancer metastases. The amelanotic character of the melanoma exerted a special diagnostic challenge. Clinical and autopsy findings as well as the immunophenotypical features of the metastatic amelanotic melanoma (HMB-45, Melan-A/MART-1, S100) and the renal cell carcinoma are described with a review of the relevant literature.

Necrotizing lymphadenitis: Kikuchi--Fujimoto disease alias lupus lymphadenitis?

Differentiation between lymphadenopathy in potentially life-threatening systemic lupus erythematosus (SLE) and self-limiting necrotizing lymphadenitis, also called Kikuchi- Fujimoto disease (KFD), is difficult. In the past, co-occurrence of SLE and KFD has been described repeatedly in case reports. Here, we report a case of necrotizing lymphadenitis, describe the clinical and histopathologic features in detail and discuss the current literature. KFD may in fact be a histopathologic characteristic of SLE supporting the hypothesis that KFD is a rare manifestation of SLE. To clarify whether KFD is the same entity as lupus lymphadenitis, more cases with SLE and lymphadenopathy should be examined in detail.

Hibernoma-like brown fat in the bone marrow: report of a unique case.

We report on a bone-marrow biopsy of a 61-year-old female patient that was performed because of the clinical suspicion of a myeloproliferative disease. The trephine biopsy showed morphological features that were consistent with an essential thrombocythaemia (ET). The diagnosis of a myeloproliferative disease could be corroborated by demonstration of the V617F mutation of JAK2. Besides the histological features of ET, the marrow showed a peculiar infiltrate that consisted of multivacuolated cells that were immunohistochemically identified as brown adipose tissue with a hibernoma-like picture. To the best of our knowledge, this is the first report on brown adipose tissue in the bone marrow.

[Hypereosinophilic syndrome and Churg-Strauss syndrome: is it clinically relevant to differentiate these syndromes?]. / Hypereosinophiles Syndrom und Churg-Strauss-Syndrom. Ist die Differenzierung der Syndrome klinisch relevant?

Churg-Strauss syndrome and the hypereosinophilic syndrome share many clinical features, particularly in the early disease stages. Beside blood and tissue eosinophilia, peripheral neuropathies, cutaneous manifestations, eosinophilic alveolitis and gastroenteritis are frequently found. In contrast to the hypereosinophilic syndrome, Churg-Strauss syndrome is defined by the presence of systemic vasculitis. However, frequently symptoms related to eosinophilia are (mis)interpreted as indirect signs of vasculitis. New treatment modalities and diagnostic methods render the early differentiation between Churg-Strauss syndrome and the hypereosinophilic syndrome increasingly clinically important. Patients with hypereosinophilic syndrome should be tested for the presence of the FIP1L1-PDGRFA-mutatition in order to identify patients that could benefit from a treatment with a tyrosine kinase inhibitor such as Imatinib. At present, immunosuppression is still the treatment of first choice for Churg-Strauss syndrome. Novel treatment modalities for both diseases include immunomodulation with interferon alpha and biologics such as antibodies against interleukin 5.

Significant high expression of CD23 in follicular lymphoma of the inguinal region.

AIMS: Inguinal lymph nodes are considered to be problematic for the diagnosis of lymphoma due to architectural changes resulting from previous inflammatory processes. The aim was to investigate the morphology and immunophenotype of follicular lymphomas (FL) in order to clarify whether FL presenting in inguinal nodes differs from FL biopsies from other sites. METHODS AND RESULTS: A total of 219 FLs were studied, comprising 78 biopsy specimens of inguinal lymph nodes and 141 from other sites. All samples were assessed for growth pattern, grade, sclerosis and immunophenotype (Bcl-2, CD10, CD23, Mib-1). Cases negative for Bcl-2 were analysed by polymerase chain reaction and fluorescence in situ hybridization. In comparison with the biopsies from other regions, we found a significantly increased number of CD23+ FLs in samples of inguinal lymph nodes (38% versus 21%). Expression of CD23 was more frequently detected in grade 1 FLs than in other grades (grade 1, 37%; grade 2, 18%; grade 3, 23%; transformed, 6%). Other immunohistochemical parameters, however, did not differ between the two groups. CONCLUSION: There is an unexpectedly high frequency of CD23 expression in FL in general, which is even more pronounced in inguinal nodes.

Cytogenetic characteristics of a murine in vitro model for the human anaplastic large cell lymphoma (ALCL).

Anaplastic large cell lymphoma (ALCL) is an entity of non-Hodgkin lymphomas (NHL) that often occurs in young children and adolescents. In the majority of cases, ALCL are of T-cell origin and contain the t(2;5)(p23;q35) leading to an NPM-ALK fusion or variant ALK translocations. In addition, there is an ALK-negative subtype of ALCL. The anaplastic lymphoid cell line TS1G6 established by interleukin (IL)-9 transfection of T-helper cells represents a murine model of this subtype. Here, we describe the cytogenetic features of this cell line using spectral karyotyping (SKY) and single-color fluorescence in situ hybridization (FISH). We show that TS1G6 cells exhibit a hypotetraploid karyotype with complex structural alterations. Several unbalanced translocations involved the chromosomal region 14E5, and different translocation partners, i.e. X?A6, 3A3 and 8A1. FISH analysis using a BAC clone containing c-myc confirmed the presence of six copies, but also demonstrated that two loci were irregularly located, indicating that additional intrachromosomal rearrangements had occurred. Moreover, a duplication of the region XF2 approximately 3 was identified. Furthermore, six chromosomes 15 were found, representing a trisomy 15 in a tetraploid chromosome complement, indicating an altered gene dosage of the oncogene c-myc located in region 15D3.

[Lymphadenoma of the parotid gland without sebaceous differentiation. Immunohistochemical investigations]. / Lymphadenom der Glandula parotis ohne Talgdrüsendifferenzierung. Immunhistochemische Untersuchungen.

An encapsulated tumor measuring 8 cm was removed from the parotid gland in a 42-year-old man. The tumor had grown for about 5 years. The histopathological and immunohistochemical evaluation revealed a lymphadenoma without sebaceous differentiation of the epithelial component. The tumor consisted of exclusively solid epithelial islands and a lymphoid stroma with rare lymph follicles and abundant predominantly IgG plasma cells. The histogenesis of lymphadenomas is discussed in consideration of the differential diagnosis from Warthin's tumor and the data in the literature.

[Anaplastic large cell lymphoma and keratoacanthoma]. / Grosszellig anaplastisches Lymphom und Keratoakanthom.

In CD30 positive lymphoproliferative disorders, e.g. anaplastic large cell lymphoma (ALCL) and lymphomatoid papulosis (LyP), pseudoepitheliomatous hyperplasia may occur in up to 50 percent of the cases. Epithelial tumors are rarely associated with ALCL or LyP, but the presence of single CD30 positive cells among the infiltrate accompanying epithelial tumors such as basal cell carcinomas and keratoacanthomas is well known. A 66-year-old man developed within a plaque of ALCL a rapidly growing epithelial tumor which we classified according to the clinical and histological features as keratoacanthoma. This case underlines the intimate interaction between CD30 positive lymphocytes and epithelial cells.

A new sarcomatoid variant of multiple myeloma in a 20-year-old male.

We present a 20-year-old man with a rare variant of multiple myeloma with peculiar spindle cell morphology and sarcomatoid growth. The diagnosis of multiple myeloma was substantiated by clinical examinations. The patient was treated with several therapeutic trials including autologous stem cell support. Unfortunately, he developed a disseminated aspergillosis of the lungs and died of fatal lung bleeding. We recommended that "sarcomatous" multiple myeloma be considered in cases of "unclassifiable" sarcomatous tumors of the bone marrow.

Rituximab induces remission in refractory HCV associated cryoglobulinaemic vasculitis.

OBJECTIVES: To report the successful induction of remission with the monoclonal anti-CD20 antibody rituximab in a patient with hepatitis C virus (HCV) associated cryoglobulinaemic vasculitis and a non-Hodgkin's lymphoma (NHL) resistant to previously advocated conventional treatments. CASE REPORT: The patient was a 45 year old woman with HCV associated cryoglobulinaemic vasculitis, with purpura, arthralgia, constitutional symptoms, and a polyneuropathy. A malignant NHL was found as underlying lymphoproliferative disease. At this stage the disease was refractory to interferon alpha2b and ribavirin and to subsequent immunosuppressive treatment with cyclophosphamide. Six rituximab infusions targeting the CD20 antigen on cells of the B cell lineage induced remission of the vasculitis. Bone marrow biopsy disclosed absence of the NHL. Remission has subsequently been maintained and HCV eliminated with the new pegylated interferon alpha2b and ribavirin for nearly one year. CONCLUSIONS: Transition of the underlying "benign" lymphoproliferative disease to a malignant lymphoma may result in difficult to treat HCV associated cryoglobulinaemic vasculitis. Rituximab offers a new possibility for inducing remission in refractory HCV associated cryoglobulinaemic vasculitis and the lymphoproliferative disorder. After remission, HCV may subsequently be eliminated with pegylated interferon alpha2b and ribavirin.

Matrix-metalloproteinases in Hodgkin lymphoma.

BACKGROUND: Classical Hodgkin lymphomas are characterized by relatively few tumour cells and prominent proliferation of plasma cells, histiocytes, lymphocytes and eosinophils. In addition there is a varying degree of sclerosis, which is especially prominent in nodular sclerosis. These morphological peculiarities led to the idea that the interaction between tumour cells and bystander cells as well as the extracellular matrix may be important in Hodgkin lymphomas. MATERIALS AND METHODS: Thirty-four classical Hodgkin lymphomas (CHL) were analysed regarding the expression of EMMPRIN, MMP-2, -7, -9, -10 and-11 using immunohistochemistry. RESULTS: The tumour cells were positive for EMMPRIN in 100% of the cases. In 82% of CHL the Hodgkin and Reed-Sternberg cells (HRS) were negative for MMP-2. In contrast the surrounding non-neoplastic cells were MMP-2-positive in 71% of the cases. The HRS cells stained positive for MMP-7 in 68% of CHL, whereas only a few surrounding cells were positive for this marker. In all but one case (97%) the HRS cells were negative for MMP-9. However, the surrounding cells stained positive in 32%, thus resembling the staining pattern for MMP-2. Only scattered cells of both populations, HRS cells as well as bystander cells, stained for MMP-10 and -11, and no specific staining pattern was observed. CONCLUSION: Our data indicate a complex interaction between tumour cells and bystander cells with regard to metalloproteinases. The expression of EMMPRIN in the tumour cells may induce the expression of MMP-2 in the surrounding non-neoplastic cells. MMP-2 can be activated by MMP-7, which is expressed in the tumour cells. It is tempting to speculate that an interruption of this cycle could be of therapeutic benefit.

[Mycosis fungoides in childhood and adolescence with clonal T-cell receptor gamma gene rearrangement. Two cases]. / Mycosis fungoides im Kindes- und Jugendalter mit klonaler Rekombination der gamma-Kette des T-Zell-Rezeptorgens. Zwei Fallberichte.

Mycosis fungoides (MF) is a cutaneous T-cell lymphoma (CTCL) characterized by its typical progress in three stages: the patch-, the plaque- and the tumour-stage. The incidence of mycosis fungoides rises with age and the average age at presentation is about 50. Children and adolescents are rarely affected and there are only few reports in the literature. We report a 12- and a 15-year-old boy showing refractory skin lesions not typical for mycosis fungoides. The histo- and immunohistological investigations and the detection of clonal T-cell receptor gamma gene rearrangements confirmed the diagnosis of early onset mycosis fungoides in both cases.