Black veins: a case of minocycline-induced pigmentation post-sclerotherapy and a review of literature.

Minocycline-induced pigmentation (MIP) is an uncommon but well-described adverse effect of oral minocycline treatment. MIP is clinically and histopathologically distinct from post-sclerotherapy pigmentation. We report a case of a patient presenting with blackened skin overlying veins recently treated with endovenous laser and foam sclerotherapy. The patient was a 44-year-old male with systemic sclerosis who commenced minocycline for the treatment of rosacea 5 months prior. Histological examination of the discolored tissue and underlying vein revealed hemosiderin deposition in the dermis and pigmented macrophages within the sub-endothelial layer of the vein wall with a staining pattern consistent with MIP. Venous tissue has not previously been reported in the literature as a target of minocycline pigmentation. Our patient preferred to control his rosacea by continuing to take minocycline. Follow-up ultrasound examinations revealed the treated vessels to be fully occluded with no evidence of recanalization, residual flow or ongoing thrombophlebitis. Despite a good sclerotherapy outcome, the pigmentation did not subside over 2 years. This case demonstrates that oral minocycline may induce significant and potentially long-term pigmentation in predisposed patients undergoing sclerotherapy.

Keratoacanthoma and infundibulocystic squamous cell carcinoma.

One of the major controversies in dermatopathology is the relationship of keratoacanthoma to squamous cell carcinoma. Leaders in the field remain polarized in their views. Carcinomas with distinct follicular pattern of differentiation have been described in reference to the isthmus as trichilemmal carcinomas, to the follicular bulb as pilomatricomal carcinomas, and to the stem cell or rapidly amplifying cell compartment as basal cell carcinomas (trichoblastic carcinomas). We have employed the term infundibulocystic or infundibular squamous cell carcinoma to identify a subset of squamous cell carcinomas that demonstrate this pattern of differentiation. The recognition of infundibular squamous cell carcinoma is important in that well-differentiated examples are likely to have been diagnosed as keratoacanthoma, whereas moderately or poorly differentiated tumors would be more often reported as squamous cell carcinomas, leading to underrecognition of these infundibular variants of squamous cell carcinoma. The descriptive term infundibulocystic or infundibular squamous cell carcinoma may help to better define an alternative follicular-based pathway to squamous cell carcinoma distinct from the more common evolution from solar keratoses and also refine the classification of keratoacanthoma.

Primary cutaneous diffuse leiomyosarcoma with desmoplasia.

A 65-year-old man presented with an indurated plaque over his left cheek and left neck. An initial punch biopsy of skin showing increased smooth muscle bundles was consistent with a diagnosis of smooth muscle hamartoma. A second incisional skin biopsy revealed a well-differentiated smooth muscle proliferation invading into the dermis and subcutaneous fat in a diffusely infiltrative pattern and with a desmoplastic component, suggesting a diagnosis of desmoplastic leiomyosarcoma. Resection of the tumour confirmed the presence of a cytologically low grade leiomyosarcoma with an insidious infiltrative growth pattern. This rare pattern of diffuse leiomyosarcoma is important to recognize as the histological features are subtle and may potentially constitute a pitfall in histological diagnosis in a small biopsy specimen. In addition, our case illustrates overlapping morphology between diffuse and desmoplastic types of leiomyosarcoma.

Therapy-related lymphomas in patients with autoimmune diseases after treatment with disease-modifying anti-rheumatic drugs.

Ten patients developing lymphomas after disease modifying anti-rheumatic drugs (DMARD) (methotrexate, n = 3, mean cumulative dose = 3.4 g; cyclophosphamide, n = 2, mean dose = 70 g; azathioprine, n = 6, mean dose = 243 g) were investigated. Methotrexate-related lymphomas were Epstein-Barr virus (EBV)-positive, had infrequent aberrant methylation of p15 and p16, and responded well to methotrexate withdrawal or anti-CD20 antibody (rituximab) alone without concomitant chemotherapy, implying that defective immunosurveillance was important in lymphomagenesis. However, 75% of cyclophosphamide/azathioprine-related lymphomas were EBV-negative, had frequent p15 and p16 methylation, and responded poorly to drug withdrawal and chemotherapy, implying that direct drug-induced mutagenesis might be involved in lymphomagenesis.

Quantification of circulating Epstein-Barr virus (EBV) DNA in the diagnosis and monitoring of natural killer cell and EBV-positive lymphomas in immunocompetent patients.

In Epstein-Barr-virus (EBV)-positive lymphomas in immunocompetent patients, release of EBV DNA from tumor cells into the plasma might be useful for disease monitoring and prognostication. To test this hypothesis, we quantified serially plasma EBV DNA by quantitative polymerase chain reaction in 39 cases of EBV-positive (natural killer [NK] cell, n = 23; T cell, n = 8; B cell, n = 4; Hodgkin, n = 4) lymphomas. As control, EBV DNA was undetectable in 34 cases of EBV-negative lymphomas at diagnosis and during chemotherapy. In all cases of EBV-positive lymphomas, EBV DNA was detectable (10(5)-10(10) copies/mL) at diagnosis. It paralleled the clinical course, with EBV DNA becoming undetectable at remission and remaining elevated in refractory disease. On multivariate analysis, high-presentation EBV DNA (> 7.3 x 10(7) copies/mL) was significantly associated with an inferior overall survival (OS). Subgroup analysis of NK cell lymphomas, the largest cohort in this study, showed that presentation EBV DNA was correlated with disease stage and lactate dehydrogenase. On multivariate analysis, high-presentation EBV DNA (> 6.1 x 10(7) copies/mL) was significantly associated with an inferior disease-free survival. During treatment, patients with EBV DNA that showed further increases or failed to become undetectable had significantly inferior OS. In EBV-positive lymphomas, plasma EBV DNA is valuable as a tumor biomarker and for prognostication.

Primary nasal natural killer cell lymphoma: long-term treatment outcome and relationship with the International Prognostic Index.

Nasal natural killer (NK) cell lymphoma is rare, so that its optimal therapy, long-term outcome, and prognostic factors are unclear. Data on 52 men and 15 women with well-characterized nasal NK cell lymphomas were analyzed retrospectively to define the impact of primary therapy on remission and long-term outcome and the validity of the International Prognostic Index (IPI). Most (84%) had stage I/II disease with an IPI score of 1 or less (52%). Seven patients received radiotherapy only; 47 patients received anthracycline-containing chemotherapy plus consolidation radiotherapy; and 12 patients received nonanthracycline-containing chemotherapy plus radiotherapy. The overall complete remission (CR) rate was 64.2%; the 20-year overall survival (OS) and disease-free survival (DFS) rates were 37.1% and 33.5%, respectively. Front-line radiotherapy was apparently better than chemotherapy for CR (100% versus 59%, P =.04) and OS (83.3% versus 32.0%, P =.03). Relapses occurred in 4 radiotherapy-treated (all local) and 14 chemotherapy-treated patients (9 local, 4 systemic). Among these, 5 late relapses (4 local, 1 systemic) occurred at 170 months (range, 92-348 months) from CR. The IPI score was of prognostic significance for the whole group (IPI or= 2 for 20-year OS: 57.4% versus 27.6%, P = 0.012), as well as for patients treated with chemotherapy/radiotherapy (IPI or= 2 for CR: 76.7% versus 35.7%, P =.017; and 10-year OS: 63.8% versus 26.8%, P =.003).

Granulomatous appendicitis progressing to Crohn's disease with bleeding complication.

Granulomatous appendicitis can be idiopathic or due to a number of specific causes. Idiopathic granulomatous appendicitis is regarded as a separate disease entity and usually has a benign course. We report on a case of granulomatous appendicitis, which progressed to fulminant Crohn's colitis shortly after appendicectomy. During the treatment with intravenous steroid, torrential gastro-intestinal bleeding developed and emergency subtotal colectomy had to be performed. The clinical and histological features of the case are presented and the literature on granulomatous appendicitis reviewed.

Aberrant promoter CpG methylation as a molecular marker for disease monitoring in natural killer cell lymphomas.

Natural killer (NK) cell lymphomas lack suitable clonal markers for tumour cell detection, making the monitoring of minimal residual lymphoma difficult. Aberrant promoter CpG methylation occurs frequently in NK cell lymphomas. The objective of this study was to assess the potential of aberrant methylation as a surrogate tumour marker. Twenty-five primary tumours and 105 serial biopsies taken at various time points after treatment were examined using a methylation-specific polymerase chain reaction (MSP) for a panel of genes, comprising p73, p16, hMLH1, RARbeta and p15, previously shown to be methylated in NK cell lymphomas. All samples underwent independent morphological examination, supplemented by immunostaining for CD56 and in-situ hybridization for Epstein-Barr-virus-encoded RNA. Primary tumours showed the frequent methylation of the genes p73 (92%), p16 (71%), hMLH1 (61%), RARbeta (56%) and p15 (48%). MSP results in serial post-treatment biopsies were correlated with clinicopathological findings. Results were concordant in 89 follow-up samples (18 samples, histology positive/MSP positive; 71 samples, histology negative/MSP negative) and discordant in 16. Fifteen samples were histology negative/MSP positive, and tumour involvement was subsequently confirmed (positive re-biopsies or relapses at the same sites), indicating that MSP was more sensitive for minimal lymphoma detection. One sample was histology positive/MSP negative; a subsequent histological review and continuous clinical remission of the patient did not support tumour involvement. Our findings suggest that MSP for aberrantly methylated genes is a potentially valuable molecular marker for detecting either residual or relapsed disease in NK cell lymphoma patients.

Cytologic and immunocytochemical findings of anaplastic large cell lymphoma: analysis of ten fine-needle aspiration specimens over a 9-year period.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) has raised much controversy in the field of hematolymphoid pathology. Its nature is becoming better characterized with recent advances in molecular genetics. However, to the authors' knowledge, a detailed description of the fine-needle aspiration (FNA) cytology of ALCL is lacking and the application of immunocytochemical study, including immunostaining for anaplastic lymphoma kinase (ALK) protein, to cytology samples has not been studied to date. METHODS: The authors reviewed 10 FNA specimens of ALCL from 8 patients encountered at Pamela Youde Nethersole Eastern Hospital and Queen Mary Hospital in Hong Kong over a 9-year period from early 1993 to the end of 2001. The cytologic and immunocytochemical findings (including ALK protein overexpression) of the specimens were correlated with histologic and immunohistochemical findings of surgical biopsy specimens. RESULTS: Six of the eight patients had ALCL of the common variant, whereas the remaining two patients had ALCL of the small cell variant. FNA specimens of ALCL of the common variant yielded many loosely dispersed "hallmark" cells that contained eccentric kidney-shaped or embryo-like nuclei, several prominent rod-shaped or angulated basophilic nucleoli, and abundant amphophilic cytoplasm. "Doughnut" cells, tumor cells with multilobated nuclei, and multinucleated giant cells with a wreath-like arrangement of nuclei occasionally were found. A small number of "plasmacytoid" tumor cells, nondescript small round tumor cells, and reactive polymorphs also was present. In contrast, "plasmacytoid" cells and nondescript small to medium-sized tumor cells represented the predominant cell population in ALCL of the small cell variant. The "plasmacytoid" appearance was exaggerated further in air-dried smears. In air-dried smears, small intracytoplasmic vacuoles and scanty azurophilic granules also were noted. On immunocytochemical study performed using the cell block materials, the majority of tumor cells demonstrated membranous and paranuclear "dot-like" positivity for CD30. The staining for epithelial membrane antigen, leukocyte common antigen, and T-cell markers was variable. Positive staining for ALK protein was demonstrated beautifully in two of the cases. CONCLUSIONS: Despite the wide morphologic spectrum of ALCL, a definitive diagnosis on the basis of FNA cytology is possible on careful interpretation of the cytologic features and a high index of suspicion. The cytologic diagnosis can be confirmed further with proper application of immunostaining to cell block sections. Immunocytochemical study for ALK protein, which provides useful prognostic information, also can be demonstrated satisfactorily using cytology samples.

Cytologic findings of angioimmunoblastic T-cell lymphoma: analysis of 16 fine-needle aspirates over 9-year period.

BACKGROUND: Peripheral T-cell lymphoma often represents an important diagnostic pitfall in fine-needle aspiration biopsy due to the heterogeneous cell population present. A classic example of this group is angioimmunoblastic T-cell lymphoma (AILD-T). The fine-needle aspiration cytology of this relatively well-defined histologic subtype of T-cell lymphoma is rarely described in the literature. METHODS: The authors reviewed 16 fine-needle aspirates of AILD-T from 9 patients in Queen Mary Hospital and Pamela Youde Nethersole Eastern Hospital, Hong Kong, over a 9-year period from early 1993 to mid-2001. The morphologic features seen in cytology smears and/or cell block sections were correlated with histologic and immunohistochemical findings of excisional biopsy specimens. RESULTS: The smears and cytospin preparations showed a heterogeneous population of hematolymphoid cells, including small lymphocytes; nondescript, medium-sized lymphoid cells; immunoblasts; plasma cells; eosinophils; and reticulum cells, including follicular dendritic cells. In general, tingible body macrophages were not identified. Conversely, follicular dendritic cells were discernible easily in most cases and sometimes were admixed intimately with lymphoid cells, forming dendritic cell-lymphocyte complexes. There also were large lymphoid tissue fragments containing a scaffold of arborizing small vessels. Pleomorphic cells with high mitotic activity or lymphoid cells with clear cytoplasm were not identified. The cell block sections often showed an intimate admixture of small lymphocytes, plasma cells, eosinophils, and reticulum cells amid a background of reticulin fibers. Lymphoid follicles with well-developed germinal centers were never found. The features seen in cytologic preparations were reminiscent of those seen in histologic sections of the corresponding lymph node excisional biopsies. CONCLUSIONS: though ancillary investigative methods, including flow cytometry and molecular study, are of limited value in fine-needle aspiration cytology assessment of AILD-T due to the heterogeneous cell population present, recognition of the peculiar combination of cytologic features, especially in the right clinical setting, should provide a clue about the diagnosis. A high index of suspicion is essential to avoid a false negative diagnosis of reactive lymphadenopathy.