Cutaneous T-cell lymphoma occurring with a melanocytic proliferation, masquerading as a nonhealing ulcer with reactive changes.

Two of the most challenging areas in dermatopathology are lymphoproliferative disorders and melanocytic lesions. We present a case of peripheral T-cell lymphoma occurring with an intradermal melanocytic proliferation. A 63-year-old Caucasian man presented with a 12-cm edematous, erythematous to violaceous, scalp ulceration that had enlarged over six months. Previous biopsies showed reactive changes which were concerning for infection. The last biopsies showed small to intermediate sized, angulated cells with clear cytoplasm within the dermis, with extension into the epidermis. These cells stained positive with markers for CD3, CD45RO and CD43, yet showed decreased expression of pan-T-cell markers CD5 and CD7, and absent expression of CD4, CD8, CD56 and CD57 and EBV. Molecular studies showed a clonal T-cell receptor gamma chain gene rearrangement. The diagnosis was peripheral T-cell lymphoma, unspecified. Another biopsy from an indurated area separate from the ulcer showed scattered, enlarged cells embedded in the same lymphocytic infiltrate. No mitotic figures were identified. These cells stained for S100 and Melan-A, in a partly nested arrangement. This was felt to represent a melanocytic nevus. This case likely represents an extraordinary coincidence of two distinctly different neoplasms.

IgG4-related meningeal disease: clinico-pathological features and proposal for diagnostic criteria.

IgG4-related disease has evolved from originally being recognized as a form of pancreatitis to encompass diseases of numerous organs including the hypophysis and one reported case of dural involvement. A search of the University of Virginia, Division of Neuropathology files for 10 years identified ten cases of unexplained lymphoplasmacytic meningeal inflammation that we then evaluated using immunohistochemical stains for IgG4 and IgG. Ten control cases including sarcoidosis (4), tuberculosis (1), bacterial abscess (2), Langerhans cell histiocytosis (2), and foreign body reaction (1) were also examined. The number of IgG4-positive plasma cells was counted in five high power fields (HPFs) and an average per HPF was calculated. Cases that contained greater than ten IgG4-positive cells/HPF were considered to be IgG4-related. Five of the study cases met these criteria, including one case of leptomeningeal inflammation. All cases exhibited the typical histological features of IgG4-related disease including lymphoplasmacytic inflammation, fibrosis, and phlebitis. The dural-based lesions appear to represent a subset of the cases historically diagnosed as idiopathic hypertrophic pachymeningitis. While the leptomeningeal process most closely resembles non-vasculitic autoimmune inflammatory meningoencephalitis. Given these findings, IgG4-related meningitis should be considered in the differential diagnosis of meningeal inflammatory lesions after stringent clinical and histologic criteria are used to rule out other possible diagnoses.

Idiopathic lymphoplasmacellular mucositis-dermatitis.

BACKGROUND: In 1952, Zoon described a series of patients with dense plasma-cell infiltrates in the glans penis. Since then, similar Zoon-like lesions (ZLL) have been described on the external female genitalia and in the airways, for which over 20 designations currently exist. METHODS: Twenty-eight cases of ZLL, twenty-two cases of lichen planus, eight cases of plasmacytoma and two cases of syphilis were evaluated from the surgical pathology archive at the University of Virginia. Twenty-four histologic data points were tabulated in each case, including 12 epidermal and 12 dermal features. RESULTS: Histopathologic findings were similar in the majority of cases of ZLL, regardless of their location. They demonstrated superficial cutaneous erosions, basal vacuolar alteration and many showed lozenge-shaped keratinocytes in the epiderms. The dermis contained a dense inflammatory infiltrate composed predominantly of plasma cells, with scattered neutrophils and lymphocytes. Dense fibrosis was seen in the upper dermis. CONCLUSIONS: A uniform nomenclature for ZLL does not exist. Based on the results of this analysis, we suggest that the generic term idiopathic lymphoplasmacellular mucositis-dermatitis be considered to encompass the lymphoplasmacellular infiltrates in the skin and mucosal surfaces considered herein. This designation is morphologically descriptive and can be applied regardless of anatomic location.

Anorectal malignant melanoma: morphologic and immunohistochemical features.

We reviewed 17 cases of primary anorectal malignant melanoma. Morphologic features evaluated included junctional change, pigmentation, morphology, and mitotic rate. Immunohistochemical stains were performed for/with S-100 protein, HMB-45, MelanA, tyrosinase, vimentin, KIT, and pankeratin. Morphologic subtypes were as follows: epithelioid, 12 cases; spindle cell, 7 cases; lymphoma-like, 10 cases; and pleomorphic, 6 cases. Pigmentation was present in 9 cases. Junctional change was present in 6 cases. The mitotic rate was 3 or more per high-power field in 8 cases. S-100 protein was present in all cases, HMB-45 stained 16 of 17, MelanA was present in 14 of 15, tyrosinase in 12 of 14, vimentin in 13 of 14, and KIT in 12 of 16. Pankeratin was absent in all cases. The mean length of follow-up was 25.6 months (range, 8-96 months), and the average survival with disease was 32.3 months (range, 8-96). No morphologic or immunohistochemical features were predictive of survival. Anorectal malignant melanoma shows considerable morphologic variability. Immunohistochemical staining is similar to cutaneous melanomas. Expression of KIT was present frequently, including cases with spindle cell morphologic features, in which it may lead to confusion with gastrointestinal stromal tumors.

Peripheral T-cell lymphomas: clinical features and prognostic factors of 92 cases defined by the revised European American lymphoma classification.

The purpose of this study was to better define the clinical features and natural history of peripheral T-cell lymphomas (PTCL) entities included in the Revised European American lymphoma (REAL) classification. Cases of PTCL were retrieved from the records of the Department of Pathology and classified according to the REAL classification. In addition, cases of anaplastic large cell lymphoma (ALCL) were divided into classical, small cell, and primary cutaneous subtypes, and immunostaining for the anaplastic large-cell kinase (ALK) protein was performed on all cases of ALCL. Clinical features, response to therapy and survival were abstracted. Ninety-two cases of PTCL with adequate clinical information were retrieved. There were 40 cases of ALCL (30 classical, 7 small cell variant, 3 primary cutaneous), 28 PTCL, unspecified, 13 angioimmunoblastic T-cell lymphoma and 11 with other entities. The patients had a median age of 48 years with a range of 6-84 and had an estimated overall survival (OS) of 49% and progression-free survival (PFS) of 22% at 5 years. The International Prognostic Index (IPI) was a significant prognostic factor for both progression-free and OS. Histology was a significant predictor of PFS with anaplastic large cell having the best prognosis. ALK expression was not associated with an improved progression-free or overall-survival in patients with systemic T-cell ALCL. In conclusion, the REAL classification describes distinct PTCL entities. The IPI is the most important predictor of progression-free and OS in patients with PTCL. ALK expression may not provide prognostic information for systemic ALCL.

BCL2 chromosomal translocation is not a general feature of the interdigitating dendritic cell sarcoma.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasia of interdigitating dendritic cells. Two single case reports documenting IDCS harboring t(14;18) translocation involving immunoglobulin heavy chain (IGH) and BCL2 have been reported recently; however, one of the 2 IDCS has a synchronous follicular lymphoma, the absence or presence of a follicular lymphoma in the remaining case is not mentioned. In this study, by using polymerase chain reaction and fluorescence in situ hybridization techniques, we have showed that there is neither t(14;18)/IGH-BCL2 nor IGH gene rearrangement in 4 de novo IDCS without a concurrent or known history of a B-cell lymphoma, including follicular lymphoma, indicating that BCL2 chromosomal translocation is not a general feature of de novo IDCS.

Primary nasopharyngeal interdigitating dendritic cell tumor presentation and response to radiation therapy.

We report the case of a primary nasopharyngeal interdigitating dendritic cell tumor (IDDCT). A 25-year old male presented with bilateral decreased hearing, double vision, and ataxia. Flexible nasopharyngoscopy reviewed a large mass obstructing and filling the entire nasopharynx. MRI and PET-CT confirmed the presence of the primary tumor and demonstrated bilateral cervical lymphadenopathy. Biopsy of the nasopharynx revealed a hematolymphoid neoplasm with dendritic cell differentiation, most consistent with an IDDCT. The lesion was unresectable. The patient was treated with definitive radiotherapy to 66 Gy to the primary tumor and 50 Gy to the bilateral cervical lymphatics using an IMRT technique. A complete response was achieved and the patient remains disease free at the primary site 23 months after completion of radiotherapy.

Posttransplantation lymphoproliferative disease involving the pituitary gland.

Posttransplantation lymphoproliferative disorders (PTLD) are heterogeneous lesions with variable morphology, immunophenotype, and molecular characteristics. Multiple distinct primary lesions can occur in PTLD, rarely with both B-cell and T-cell characteristics. Lesions can involve both grafted organs and other sites; however, PTLD involving the pituitary gland has not been previously reported. We describe a patient who developed Epstein-Barr virus-negative PTLD 13 years posttransplantation involving the terminal ileum and pituitary, which was simultaneously involved by a pituitary adenoma. Immunohistochemistry of the pituitary lesion showed expression of CD79a, CD3, and CD7 with clonal rearrangements of both T-cell receptor gamma chain (TRG@) and immunoglobulin heavy chain (IGH@) genes. The terminal ileal lesion was immunophenotypically and molecularly distinct. This is the first report of pituitary PTLD and illustrates the potentially complex nature of PTLD.

Detection of immunoglobulin heavy chain gene rearrangements in classic hodgkin lymphoma using commercially available BIOMED-2 primers.

CONTEXT: Classic Hodgkin lymphoma (cHL) is regarded as a clonal B-cell neoplasm. The BIOMED-2 group recently validated a set of immunoglobulin heavy chain (IGH) multiplex primers with high sensitivity in B-cell non-Hodgkin lymphomas. We postulated that after using these primers, a higher proportion of the cHLs would have detectable rearrangements without microdissection. DESIGN: Forty-two patients with cHL were selected. The densities of Reed-Sternberg cells/10 high-power field and CD30+ cells/10 high-power field were classified as low, intermediate, or high. The quantities of background CD20+ B cells were classified as low or high. DNA from formalin-fixed, paraffin-embedded sections was used to perform polymerase chain reactions with the InVivoScribe IGH Gene Clonality Assay for ABI detection. Dominant peaks were considered to be monoclonal if they were >3x the height of the polyclonal background, and borderline monoclonal if between 2 and 3x. RESULT: Overall, 10/42 (24%) of the cHL samples were monoclonal, and 7/42 (17%) were borderline monoclonal. Higher densities of CD30+ cells and lower background B cells were statistically correlated with clonality. CONCLUSIONS: The BIOMED-2 primers demonstrate IGH gene clonality in 24% to 40% of cHLs without microdissection. In a subset of the cHL, the IGH gene rearrangement analysis might be useful for diagnosis, but can lead to confusion between cHLs and non-Hodgkin lymphomas if used as a discriminative criterion.

Rituximab-CD20 complexes are shaved from Z138 mantle cell lymphoma cells in intravenous and subcutaneous SCID mouse models.

Infusion of standard-dose rituximab (RTX) in chronic lymphocytic leukemia (CLL) patients promotes rapid complement activation and deposition of C3 fragments on CLL B cells. However, immediately after RTX infusions, there is substantial loss (shaving) of CD20 from circulating malignant cells. Because shaving can compromise efficacies of anticancer immunotherapeutic mAbs, we investigated whether shaving occurs in SCID mouse models. Z138 cells, a B cell line derived from human mantle cell lymphoma, were infused i.v. or s.c. The i.v. model recapitulates findings we previously reported for therapeutic RTX in CLL: i.v. infused RTX rapidly binds to Z138 cells in lungs, and binding is accompanied by deposition of C3 fragments. However, within 1 h targeted cells lose bound RTX and CD20, and these shaved cells are still demonstrable 40 h after RTX infusion. Z138 cells grow in tumors at s.c. injection sites, and infusion of large amounts of RTX (0.50 mg on each of 4 days) leads to considerable loss of CD20 from these cells. Human i.v. Ig blocked shaving, suggesting that FcgammaRI on cells of the mononuclear phagocytic system promote shaving. Examination of frozen tumor sections from treated mice by immunofluorescence revealed large areas of B cells devoid of CD20, with CD20 intact in adjacent areas; it is likely that RTX had opsonized Z138 cells closest to capillaries, and these cells were shaved by monocyte/macrophages. The shaving reaction occurs in neoplastic B cells in tissue and in peripheral blood, and strategies to enhance therapeutic targeting and block shaving are under development.

Follicular lymphoma of the dura: case report.

OBJECTIVE: We present an unusual dural-based follicular lymphoma with radiological and macroscopic features similar to a meningioma. The unusual location of this tumor and its distinction from meningioma, mucosa-associated lymphoid tissue-type marginal zone B-cell lymphoma of the dura, and intraparenchymal central nervous system lymphoma, dramatically alters the patient's postoperative treatment. The case illustrates the clinical, radiological, and histological relevance of this rare entity. CLINICAL PRESENTATION: A 41-year-old Caucasian man with chronic bifrontal headaches and a raised area over his left frontal cranium that persisted for 1 year presented to the emergency room with nausea and vomiting. His family reported that the patient demonstrated increased irritability and aggressive behavior. A computed tomographic scan revealed a large mass of the left frontal convexity with edema and mass effect. Magnetic resonance imaging scans showed a 5-cm homogeneously enhancing mass in the left posterior frontal lobe. INTERVENTION: Preoperatively, the patient underwent angiography and embolization of the tumor. The patient underwent gross total resection of tumor. The dural-based tumor invaded the cranium and scalp. Neuropathological findings were consistent with low-grade follicular lymphoma. The patient is currently undergoing radiation and chemotherapy. CONCLUSION: The current case represents the first report of extensive intracranial dural involvement by a follicular lymphoma that shows a classic immunophenotype by immunohistochemistry and flow cytometry. The case illustrates the clinical and radiographic similarities between dural-based lymphoma and meningioma. Distinguishing dural-based follicular lymphoma from mucosa-associated lymphoid tissue-type lymphoma and from intraparenchymal primary central nervous system lymphomas, which are more often large cell lymphomas with more aggressive biological behavior, is essential for proper clinical management.