Dermatopathic Lymphadenopathy Research Articles

Specificity of the histopathological triad for the diagnosis of toxoplasmic lymphadenitis: polymerase chain reaction study.

Toxoplasmosis is a common cause of lymphadenopathy, but toxoplasmic cysts are not usually found in histological sections used for establishing diagnosis, except on extremely rare occasions. The histopathological triad of florid reactive follicular hyperplasia, clusters of epithelioid histiocytes, and focal sinusoidal distention by monocytoid B cells has been considered to be diagnostic of toxoplasmic lymphadenitis, but the validity of the histopathological triad is based indirectly on serological correlation only. The demonstration of Toxoplasma gondii DNA in lymph nodes displaying the histopathological triad will indicate the validity of the histopathological triad as the criterion for the histopathological diagnosis of toxoplasmic lymphadenitis. We used frozen tissues of 12 lymph nodes with the histopathological triad and tissues of 27 lymph nodes from patients with various other conditions (including 13 cases of follicular lymphoid hyperplasia, FLH; three cases of dermatopathic lymphadenopathy, DPL; two cases of plasmacytosis; two cases of Castleman's disease; two cases of metastatic adenocarcinoma; and five cases of lymphoma) to detect T. gondii DNA by polymerase chain reaction. Ten out of 12 lymph nodes with the triad and six out of 27 lymph nodes without the triad were positive for T. gondii DNA. Thus, the sensitivity of the triad was 62.5% (10/16) and the specificity was 91.3% (21/23). The predictive value of positive tests was 83.3% (10/12) and the predictive value of negative tests was 77.7% (21/27). The six cases positive for T. gondii DNA without the triad were four cases of FLH, one case of DPL, and one case of plasmacytosis. None of the neoplastic diseases was positive. The false positive and negative cases could be due to sampling problems or past T. gondii infection. The results confirm that the histopathological triad is highly specific for the diagnosis of toxoplasmic lymphadenitis and can be used confidently.

Langerhans Cell Histiocytosis in Lymph Nodes

To delineate the cytomorphology of Langerhans cell histiocytosis (LCH) in lymph nodes. Nine histologically documented LCH cases with a prior lymph node aspirate and five more cases in which a cytologic diagnosis of LCH was rendered in a background of corroborative clinical and radiologic findings were included in a retrospective study over a 12-year period (January 1988-January 2000). Papanicolaou- and May-Grünwald-Geimsa-stained smears were reviewed by two independent observers. Staining for S-100 protein was available in four cases. Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. The ages ranged from 5 months to 27 years, with 11 males and 3 females. An initial cytologic diagnosis of LCH had been rendered in six, suspected in four and missed in four. On review, all were reclassified as LCH except two cases, which were still thought to be reactive and necrotizing lymphadenitis. The pathognomic feature of LCH, the "LCH cell," was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in six cases, and plasma cells were rarely seen. Lymph node involvement by LCH can be identified by fine needle aspiration in 85% of cases. The presence of the LCH cell is a must. The differentials to be considered are dermatopathic lymphadenitis, sinus histiocytosis with massive lymph-adenopathy, Hodgkin's lymphoma and malignant histiocytosis.

Prevalence of Bartonella henselae in granulomatous lymphadenitis: A useful tool for the diagnosis of cat-scratch disease by polymerase chain reaction.

Bartonella Henselae is the causative agent of human cat-scratch disease (CSD). CSD can be diagnosed by histopathological examination, and by the enzyme immunoadsorbant assay (EIA) and polymerase chain reaction (PCR) methods, which detect B. Henselae DNA. Histopathological findings of CSD include granulomatous lymphadenitis with or without abscess formation. We examined 36 specimens of granulomatous lymphadenitis, including 15 abscess-forming granulomatous lymphadenitis, 9 non-abscess-forming granulomatous lymphadenitis, 10 tuberculosis and 2 sarcoidosis by PCR with primers specific for B. Henselae and Bartonella quintana. As controls, we examined 79 cases of non-granulomatous lymphadenitis, including 7 with dermatopathic lymphadenopathy, 18 Kikuchi's lymphadenitis (histiocytic necrotizing lymphadenitis), 18 follicular hyperplasia, 18 paracortical hyperplasia and 18 non-specific lymphadenitis. The PCR method identified B. henselae in 10 of 15 (67%) patients with abscess-forming granulomatous lymphadenitis and 2 of 9 (22%) with non-abscess-forming granulomatous lymphadenitis, but none in tuberculosis, sarcoidosis and non-granulomatous lymphadenitis. B. henselae was persistently detected in all but one patient from the appearance of symptoms to 4 months from onset in patients with abscess-forming and non-abscess-forming granulomatous lymphadenitis. Our results suggest that the PCR method is useful for establishing the diagnosis of CSD by detecting B. henselae.

Langerhans cell histiocytosis in lymph nodes - cytomorphological diagnosis and pitfalls

Background Langerhans cell histiocytosis (LCH) is a rare disorder of unknown aetiology that may present as a multisystem or unisystem disease. The Lymph nodes can be involved as part of disseminated disease, as a metastatic site draining a focus of LCH or may be a unisystem involvement. Paucity of literature on the cytomorphology of LCH in lymph nodes led us to undertake this study. Materials and methods Nine cases with a confirmed histological diagnosis of LCH and a prior lymph node aspirate were retrieved over a 12 year period (1988–1999). Five more cases were reviewed where the cytological diagnosis of LCH was rendered on a background of clinical and radiological findings. Papanicolaou and May Grunwald–Giemsa-stained smears were examined. S-100 protein staining was available in four cases. Results and conclusions Nine cases had multisystem involvement, while in five cases only lymph nodes were involved. There were eleven males and three females; age ranged from five months to 27 years. The cytological diagnosis of LCH had been rendered in six, suspected in four and missed in four. Of the latter, two were reclassified as LCH on review, one as reactive lymphadenitis and in one a necrotising lesion was suspected. The pathognomonic ‘LCH cell’ was identified in 12 of 14 cases along with varying numbers of eosinophils, polymorphs and lymphocytes. Giant cells were seen in only six cases. In conclusion lymph node involvement by LCH can be identified on aspirates. However, LCH must be differentiated from dermatopathic lymphadenitis, sinus histiocytosis with massive lymphadenopathy and Hodgkin's disease.

Aspiration biopsy and the clinical management of patients with malignant melanoma and palpable regional lymph nodes.

The presence of lymph node metastases in patients with malignant melanoma implies a significant decrease in survival. The authors investigated the efficacy of fine-needle aspiration biopsy (FNAB) in the diagnosis of metastatic malignant melanoma in 115 patients with melanoma and clinically suspicious regional lymph nodes. One hundred thirty-three FNABs were performed by cytopathologists after referral from surgeons or oncologists using a 25-gauge or 27-gauge needle. The cytologic diagnosis was negative in 35, atypical in 1, suspicious in 2, and positive for malignant melanoma in 95. Regional lymph node dissections were performed in 78 patients. Of these, 70 positive FNABs were confirmed with no false-positive results. The atypical FNAB was proven positive for malignant melanoma at surgery. Of the two suspicious FNABs, one was confirmed as positive and one showed dermatopathic lymphadenopathy. Of the 35 negative FNAB specimens, 5 patients underwent surgery; 3 FNABs were found to be negative and 2 FNABS were falsely negative. Twenty patients with negative aspirates were followed clinically for 22-45 months (mean, 32 months); 19 patients had no evidence of disease and 1 patient died of disseminated melanoma. FNAB of palpable lymphadenopathy in patients with malignant melanoma can provide a rapid and accurate assessment of lymph node status and expedite the therapeutic management of these patients.

Paracortical hyperplasia of superficial lymph nodes in a new mutant strain of hairless rats (ISh): a lesion similar to human dermatopathic lymphadenopathy.

The dermal histology and the regional draining superficial lymph node of a new mutant strain of hairless rats (ISh) were investigated. The homozygote ISh rat was characterized as having naked and wrinkled skin. The comedo-like cysts in the skin resembled human acne and vulgaris. Histopathologically, many Langerhans' cells positive for anti-protein kinase C type II antibody (PKC-II) were recognized in the epidermis. The superficial lymph nodes were significantly larger than those of the heterozygote. The paracortex of these lymph nodes was expanded and the number of Langerhans' cells mainly increased in these areas. These lymph node lesions were similar to those of human dermatopathic lymphadenopathy. The ISh rats should be a very useful animal model for studying dermatopathic lymphadenopathy in humans. Furthermore, they may be a valuable animal model for investigating the mechanisms of not only maturation, movement and migration of Langerhans' cells, but also of their function for antigen presentation.

Human cytomegalovirus infection in foci of Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) has been thought to be a disorder of immune regulation, and increasingly, evidence showing that the tissue damage in LCH involves lymphokines and pro-inflammatory cytokines is reported. We detected human cytomegalovirus (HCMV)-DNA in LCH cells in the foci of LCH lesions by immunohistochemistry, in situ hybridization and PCR. HCMV was detected in the nuclei and/or cytoplasm of LCH cells in 9 of 27 LCH cases by immunostaining. HCMV was probably an early antigen. In situ hybridization revealed signals for HCMV-DNA only in the nuclei of LCH cells in 10 of the 27 LCH cases. PCR analysis was performed in 20 of the LCH cases, and HCMV-DNA was detected in 7 of these. All 7 positive cases were also positive for HCMV by ISH and IHC. These findings suggested that early phase infection or reactivation of HCMV occurred in the LCH lesions. HCMV infection may be accompanied by impaired cytokine production. Our study also suggested a relationship between HCMV infection and expression of TNFalpha. In tissues affected by LCH, dermatopathic lymphadenopathy or malignant fibrous histiocytoma and in normal tissues no signals for Epstein-Barr virus-RNA were detected. These findings suggest that in some cases LCH is associated with HCMV infection.

Fine Needle Aspiration Cytology of Dermatopathic Lymphadenitis

To delineate and describe the cytomorphologic features of dermatopathic lymphadenitis on fine needle aspirated material. Thirteen cases of previously diagnosed dermatopathic lymphadenitis (DLN) and 10 cases of reactive lymphadenitis (RLN) (5 each of sinus histiocytosis and follicular hyperplasia) were reexamined by two independent observers. The cytologic features were semiquantitated (0-3+). Histology was available in two cases. A variable amount of melanin pigment was seen in all 13 cases of DLN and in only 3 cases of RLN. DLN had large histiocytic collections with blood vessels at the center (12/13). The histiocytic cells had an elongated nucleus (13/13) with nuclear grooves (13/13) and pseudonucleoli (11/13). Many of these nuclei had a convoluted and crumpled appearance (11/13). On immunocytochemistry these cells were S-100 positive (six cases) and CD68 negative (one case). In contrast, in RLN with sinus histiocytosis, the histiocytes were polygonal and had rounded nuclei. Spindle-shaped histiocytes were rare, while pseudonucleoli and nuclear grooves were absent. Sinus histiocytes were CD68 positive and S-100 negative on histologic sections. Tingible body macrophages were rare (2/13) in DLN and prominent (8/10) in RLN. Mitoses were seen in DLN (6/13) and RLN (9/10). The morphologic features found to be helpful in the diagnosis of DLN on fine needle aspiration cytology are melanin-laden macrophages with variable pigment; large, histiocytic clusters with blood vessels at the center; characteristic histiocytes, with elongated vesicular nuclei, nuclear grooves, crumpled and convoluted nuclei and pseudonucleoli; and absence of or very few tingible body macrophages. Positivity on immunostaining for S-100 and negativity for CD68 aid in the diagnosis.

T-cell receptor gene rearrangement analysis in the primary cutaneous T-cell lymphoma

Object: The present paper is to evaluate the significance of T-cell receptor (TCR) gene rearrangements in primary cutaneous T-cell lymphomas (PCTCL) as detected by analysis of Southern Blot (SBA) and polymerase chain reaction (PCR). Patients and Methods: Skin specimens and peripheral blood samples were taken from 44 patients with PCTCL, including 30 patients with mycosis fungoides (MF), 2 patients with Sezary's syndrome (SS), and 12 patients with PCTCL other than MF and SS (PNCTCL). 11 patients with a presumptive diagnosis of MF, 23 patients with lymphoproliferative dermatoses including lymphomatoid papulosis (LyP) and 8 patients with benign cutaneous lymphoid infiltrates were simultaneously studied by the ampfification of junctional V (variable)-J (joining) sequences of the rearranged TCR T genes by PCR(TCRγPCR) and the analysis of TCRβ-chain genes by SBA(TCRβSBA) for detection of clonal gene rearrangements (GR). One lymph node specimen of a case with MF IIA was also detected by TCRγPCR and TCRβSBA. Results: In MF, GR were detected by TCRγPCR and TCRβSBA[3 in 83.3- 85.7% and 66.7%-71.4% of skin specimens of cases IIAliB and in 57.1%-70.0% and 14.3%-10.0% of those of cases IA-IB, respectively. GR were seen in 66.7%- 71.4% and 33.3%-43.0.% of blood samples of cases IIAliB, and 42.9%-40.0% and 0-10.0% of those of cases IAIB, respectively. GR was confirmed by TCRγPCR and TCRβSBA in one lymph node showing dermatopathic lymphadenopathy of a case with MF IIA. In 11 patients of clinically suspected MF, GR were present in skin specimens of 5 cases (45.4%) and in blood samples of 3 cases (27.3%) by TCRγPCR. In PNCTCL, GR were found in 9 skin specimens (90.0%) from 10 patients detected by TCRγPCR and in 6 skin specimens (75.0%) from 8 patients detected by TCRβSBA. GR were also seen in 6 blood samples (72.8%) from 11 patients detected by TCRγPCR, and in 7 blood samples (70.0%) from 10 patients by TCRβSBA. In SS and LyP, GR were detected by TCRγPCR and TCRβSBA in each of the two skin specimens of two cases with LyP and in each of the two blood samples of two cases with SS. GR were seen in one skin specimen of one case with SS and one blood sample of one case with LyP detected by TCRγPCR. Conclusions: This study demonstrated that TCRγPCR is a rapid, more sensitive tool than TCRβSBA, can be used in the analysis of T-cell clonality in skin, lymph node and blood samples of patients with PCTCL and indicated that this method forms a useful supplement to other methods for diagnosis of early and suspected MF, confirmation of PNCTCL and determination of extracutaneous involvement of lymph node and blood.

Somatostatin receptor scintigraphy in cutaneous malignant lymphomas

Background: Lymphoid cells may express somatostatin receptors (SS-Rs) on their cell surface. Therefore radiolabeled somatostatin analogues may be used to visualize SS-R—positive lymphoid neoplasms in vivo. Exact staging is the basis for treatment decisions in cutaneous malignant lymphoma. We considered the possibility that SS-R scintigraphy might offer a clinically useful method of diagnostic imaging in patients with cutaneous malignant lymphoma. Objective: We evaluated SS-R scintigraphy in comparison with conventional staging methods in the staging of cutaneous malignant lymphoma. Methods: We conducted a prospective study in 14 consecutive patients with histologically proven cutaneous malignant lymphoma. SS-R scintigraphy was compared with physical, radiologic, and bone marrow examinations. Lymph node excisions were performed in patients with palpable lymph nodes. Results: SS-R scintigraphy was positive in the lymph nodes in all four patients with malignant lymph node infiltration and negative in the three patients with dermatopathic lymphadenopathy. In two patients, previously unsuspected lymphoma localizations were visualized by SS-R scintigraphy. In only three patients all skin lesions were visualized by SS-R scintigraphy; these three patients had not been treated with topical corticosteroids. SS-R scintigraphy failed to detect an adrenal mass in one patient and bone marrow infiltration in two patients. Conclusion: SS-R scintigraphy may help distinguish dermatopathic lymphadenopathy from malignant lymph node infiltration in patients with cutaneous malignant lymphoma.

MONOKINE EXPRESSION IN LANGERHANS' CELL HISTIOCYTOSIS AND SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY (ROSAI-DORFMAN DISEASE)

Langerhans' cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells (LC) showing histologically an abundant reactive infiltrate composed of macrophages and lymphocytes, as well as eosinophilic and neutrophilic granulocytes. Rosai-Dorfman disease (RDD) shows a sinusoidal accumulation of large histiocytic cells with an immunophenotype similar to LC of LCH. The histological picture of LCH is reminiscent of an inflammatory disorder and LC may produce cytokines and are influenced by these soluble factors. This study set out to establish the monokine expression pattern in LCH in comparison with those of RDD; dermatopathic lymphadenopathy, which also shows a proliferation of S100-positive dendritic cells; and LC in normal skin specimens. Isotopic in situ hybridization was used for the detection of transcripts of tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and IL-1 beta, in some cases combined with immunohistology for the S100 protein or CD68. In all 11 tissue samples from eight patients, LC of LCH expressed TNF-alpha; in two cases IL-1 beta transcripts were additionally noted in some LC, whereas IL-6 was found in reactive cells. Large histiocytic cells of RDD expressed all three monokines, whereas minimal or no expression of these cytokines could be detected in interdigitating reticulum cells in dermatopathic lymphadenopathy. In two out of five normal skin samples, only TNF-alpha specific signals were observed in LC. These data suggest that histologically different lesions of the histiocytic/dendritic cell system display distinct cytokine profiles. The expression of monokines, which have been demonstrated to influence various functions of epidermal LC, may play a role in the pathogenesis of LCH. Systemic symptoms in RDD may be related to enhanced production of monokines in these lesions.

MONOKINE EXPRESSION IN LANGERHANS' CELL HISTIOCYTOSIS AND SINUS HISTIOCYTOSIS WITH MASSIVE LYMPHADENOPATHY (ROSAI–DORFMAN DISEASE)

Langerhans' cell histiocytosis (LCH) is a clonal proliferation of Langerhans cells (LC) showing histologically an abundant reactive infiltrate composed of macrophages and lymphocytes, as well as eosinophilic and neutrophilic granulocytes. Rosai–Dorfman disease (RDD) shows a sinusoidal accumulation of large histiocytic cells with an immunophenotype similar to LC of LCH. The histological picture of LCH is reminiscent of an inflammatory disorder and LC may produce cytokines and are influenced by these soluble factors. This study set out to establish the monokine expression pattern in LCH in comparison with those of RDD; dermatopathic lymphadenopathy, which also shows a proliferation of S100-positive dendritic cells; and LC in normal skin specimens. Isotopic in situ hybridization was used for the detection of transcripts of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, in some cases combined with immunohistology for the S100 protein or CD68. In all 11 tissue samples from eight patients, LC of LCH expressed TNF-α; in two cases IL-1β transcripts were additionally noted in some LC, whereas IL-6 was found in reactive cells. Large histiocytic cells of RDD expressed all three monokines, whereas minimal or no expression of these cytokines could be detected in interdigitating reticulum cells in dermatopathic lymphadenopathy. In two out of five normal skin samples, only TNF-α specific signals were observed in LC. These data suggest that histologically different lesions of the histiocytic/dendritic cell system display distinct cytokine profiles. The expression of monokines, which have been demonstrated to influence various functions of epidermal LC, may play a role in the pathogenesis of LCH. Systemic symptoms in RDD may be related to enhanced production of monokines in these lesions.

Differentiation of Langerhans cells from interdigitating cells using CD1a and S-100 protein antibodies.

The present study shows that Langerhans cells can be differentiated from interdigitating cells at the light microscopic level. Superficial lymph nodes and skin taken from necropsies and the lymph nodes of dermatopathic lymphadenopathy (DPL) were used for this experiment. Sections of lymph node and skin were embedded using the acetone, methyl benzoate and xylene (AMeX) method and dendritic cells were immunostained with anti S-100 protein antibody (S-100, and OKT-6 (CD1a) using the restaining method. Langerhans cells in the skin were positive for both CD1a and S-100. Dendritic cells positive for both CD1a and S-100, and dendritic cells positive for S-100, but not for CD1a were observed in superficial lymph nodes. In normal superficial lymph nodes, there were more interdigitating cells than Langerhans cells. The majority of the dendritic cells in the DPL were Langerhans cells. We conclude that the S-100 and CD1a positive cells are Langerhans cells, and the S-100 positive-CD1a negative cells are interdigitating cells.

Cathepsin D and E co-expression in sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) and Langerhans' cell histiocytosis: further evidences of a phenotypic overlap between these histiocytic disorders.

Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence.

皮膚病性リンパ節症，Ｈｉｓｔｉｏｃｙｔｏｓｉｓ Ｘにおける樹状細胞の研究

Langerhans cells (LCs) and interdigitating cells (IDCs) are said to have the same morphological and immunological characteristics. We have reported on Birbeck granules (BG)-bearing LCs, which are positive for both OKT-6 (CD1a) and anti S-100 protein antibodies, and IDCs which are only positive for S-100 protein, but negative for OKT-6. In this paper, we examined the characteristics of dendritic cells in dermatopathic lymphadenopathy (DPL) and Histiocytosis X (HCX) using immunohistochemical and immuno-electron microscopic techniques. The majority of the dendritic cells which existed in the lymph nodes of DPL were positive for OKT-6. We concluded that these dendritic cells were not IDCs, but LCs. Electron microscopically, LCs in these lymph nodes contained only a few BG. Most of the LCs were negative for PCNA antibody. This finding means that the proliferative activity of these LCs is very low and that they do not divide or proliferate in the lymph nodes. On the other hand, HCX is considered to be a rare proliferative disorder of LCs. HCX cells were positive for S-100, OKT-6, CD4 (Leu3a) and HLA-DR (Ia), in addition they were highly positivity for PCNA. These findings indicate that HCX cells originate in immature cells which are already part of the Langerhans cell lineage.

Immunohistochemical detection of CD1A antigen in formalin-fixed and paraffin-embedded tissue sections with monoclonal antibody 010.

The immunoreactivity of a CD1a monoclonal antibody (MAb), denoted 010, was investigated by means of the streptavidin-biotin-peroxidase method in formalin-fixed and paraffin-embedded tissues from 47 cases. The samples comprised reactive lymphoid proliferations of skin, tonsil, and lymph node including dermatopathic lymphadenopathy and Langerhans' cell histiocytosis, Hodgkin's and non-Hodgkin's lymphomas, and thymomas. Interdigitating and dermal dendritic cells, veiled cells, Langerhans' cells, and also cortical thymocytes and their neoplastic counterparts displayed immunostaining with MAb 010 in paraffin sections. These results are identical to previous ones reported for other CD1a MAbs in fresh or frozen specimens. The findings suggest that the binding site of 010 is a fixation-resistant epitope of CD1a antigen which has not been previously identified.

Diagnostic and prognostic significance of clonal T‐cell receptor beta gene rearrangements in lymph nodes of patients with mycosis fungoides

In this study, 25 involved and uninvolved lymph nodes from 22 patients with mycosis fungoides (MF) and seven dermatopathic lymph nodes from patients with benign skin disorders were studied for the presence of clonal T-cell receptor beta (TCR beta) gene rearrangements by Southern blot analysis. These results were correlated with the histological classification, follow-up data, and survival. The results of the histological classification and Southern blot analysis were concordant in 26 of 32 cases. Clonal TCR beta gene rearrangements were found in all six MF lymph nodes showing (partial) effacement of the normal lymph node architecture, but in none of the eight uninvolved dermatopathic MF lymph nodes and in none of the seven dermatopathic control lymph nodes. In addition, in 5 of 11 dermatopathic MF lymph nodes that were considered to have early involvement by MF at histological examination, clonal TCR beta gene rearrangements were detected. In the group of MF patients with dermatopathic lymphadenopathy, patients with detectable clonal T-cell populations had a significantly shorter survival than patients without such a population (P < 0.01). The results of this study indicate that within the group of dermatopathic MF lymph nodes, prognostically different groups can be distinguished and that TCR beta gene rearrangement analysis may be an important adjunct in the early diagnosis of lymph node involvement by MF.

Lymph Node Histopathologic Findings in Cutaneous T-Cell Lymphoma: A Prognostic Classification System Based on Morphologic Assessment

The histopathologic features of 251 lymph nodes obtained from 200 patients with various clinical expressions of cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome) were reviewed retrospectively. Lymphomatous involvement, defined as partial or complete effacement of lymph node architecture by malignant cells, was identified in 89 specimens (35%) and was characterized by morphologic variability from case to case. The involved specimens were classified into four major histologic subtypes according to the morphologic appearance of the malignant cells in a manner analogous to a modified Rappaport classification of diffuse non-Hodgkin's lymphomas. Although lymph node involvement was associated with a poor prognosis regardless of histologic subtype, the survival of patients with small cell (cerebriform) subtype was found to be significantly better (median survival time, 40 months) than other subtypes (median survival time, 20 months), possibly because this type of involvement sometimes preceded the development of the more aggressive mixed and large cell subtypes. Dermatopathic lymphadenopathy compared to other reactive patterns had no special prognostic importance other than its more frequent occurrence in black patients and in patients with more extensive skin involvement.

Syndrome of severe skin disease, eosinophilia, and dermatopathic lymphadenopathy in patients with HTLV-II complicating human immunodeficiency virus infection

Two intravenous drug users dually infected with human immunodeficiency virus type 1 (HIV-1) and human T-cell leukemia virus type II (HTLV-II) developed an unusual severe dermatitis characterized by progressive brawny induration, fissuring, and ulceration of the skin, with an associated CD8 cell infiltration in one patient. Both patients had persistent eosinophilia. Lymph node biopsy revealed dermatopathic lymphadenopathy, an unusual pathologic finding in HIV-1 infection but one seen in association with mycosis fungoides and other skin disorders. Two new isolates of HTLV-II virus were established from these patients and were identified as HTLV-II by Southern blotting. This type of skin disease and lymph node pathology has not been found in other intravenous drug users who have been infected with HIV-1 alone or in patients in other risk groups for HIV-1 infection. HTLV-II may play a role in this unique new disease pattern in patients infected with HIV-1.

Evaluation of Biotinylated DNA Probes for the Detection of Gene Rearrangements in Clinical Specimens

To determine whether a nonisotopic procedure is suitable for analyzing clinical specimens for gene rearrangements, the authors hybridized DNA from 15 specimens of lymphoid tissue with biotinylated DNA probes directed to J beta I + J beta II (T-cell receptor beta chain gene), JH (immunoglobulin gene heavy chain J region), and J kappa (immunoglobulin gene kappa light chain J region). Five cases of benign lymphoid hyperplasia, one case of dermatopathic lymphadenopathy, and one case of small noncleaved follicular center cell lymphoma had germline hybridization patterns when digested with Bam HI, Eco RI, and Hind III restriction endonucleases. Four cases of B-cell lymphoma and three cases of T-cell lymphoma had clearly detectable rearrangements of the genes for immunoglobulin or the T-cell receptor or both. One case of dermatopathic lymphadenopathy had a faint, clonal rearrangement of the T-cell receptor after digestion with Eco RI and Bam III. The authors conclude that biotinylated DNA probes can be useful for analyzing gene rearrangements in clinical specimens.