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Biomedical subjects

J K Chan

Publications and source records attributed to J K Chan.

At least 19 recordsLinked to original sources

Epstein-Barr virus-associated Hodgkin's disease: epidemiologic characteristics in international data.

Hodgkin's disease (HD) has long been suspected to have an infectious precursor, and indirect evidence has implicated Epstein-Barr virus (EBV), a ubiquitous herpesvirus, as a causal agent. Recent molecular studies using EBER in situ hybridization or latency membrane protein-I (LMP-I) immunohistochemistry have identified EBV latent infection in up to 50% of HD tumors. However, the epidemiologic features of these cases have not been examined in detail. To explore the epidemiology of EBV-positive HD so as to understand the role of EBV in HD etiology more clearly, this project accumulated patient data from 14 studies that had applied these EBV assays to HD tumors. With information on age at diagnosis, sex, ethnicity, histologic subtype, country of residence, clinical stage and EBV tumor status from 1,546 HD patients, we examined risk for EBV-positive disease using logistic regression. Forty percent of subjects had EBV-positive tumors, and EBV prevalence varied significantly across groups defined by the study variables. Odds ratios (OR) for EBV-associated HD were significantly elevated for Hispanics vs. whites (OR = 4.1), mixed cellularity vs. nodular sclerosis histologic subtypes (OR = 7.3, 13.4, 4.9 for ages 0-14, 15-49, 50+ years), children from economically less-developed vs. more-developed regions and young adult males vs. females (OR = 2.5). These findings suggest that age, sex, ethnicity and the physiologic effects of poverty may represent biologic modifiers of the EBV association and confirm that this association is strongly but variably linked to histologic subtype. The data augment biologic evidence that EBV is actively involved in HD pathogenesis in some cases but describe epidemiologic complexity in this process.

Adolescent

Follicular dendritic cell sarcoma. Clinicopathologic analysis of 17 cases suggesting a malignant potential higher than currently recognized.

BACKGROUND: The goal of this study was to characterize the clinicopathologic features of follicular dendritic cell sarcoma, a very uncommon neoplasm. METHODS: The 17 cases were collected from the consultation and surgical pathology files of the authors, including 8 previously reported cases. The histologic and immunohistochemical features and outcome were analyzed. RESULTS: The patients had a median age of 40 years, with a slight female predominance. Seven patients presented with enlarged lymph nodes, and ten presented with tumor in extranodal sites. Two cases were associated with hyaline-vascular Castleman's disease. The tumors had an average greatest dimension of 6.7 cm. The most common histologic feature was a storiform or fascicular array of spindle, ovoid, or polygonal cells with oval nuclei, delicate nuclear membrane, vesicular or granular chromatin, distinct nucleoli, indistinct cell borders, and frequently fibrillary cytoplasm. There were often scattered multinucleated forms. The tumor cells sometimes formed sheets, circular whorls, follicle-like structures, trabeculae, or pseudovascular spaces. There was a sprinkling of small lymphocytes, with or without cuffing around blood vessels. The neoplastic cells were immunoreactive for CD21 (17 of 17 cases), CD35 (17 of 17 cases), desmoplakin (10 of 17 cases), epithelial membrane antigen (14 of 16 cases), S-100 protein (6 of 17 cases), and CD68 (2 of 17 cases), but not cytokeratin. Ultrastructural studies showed villous processes connected by desmosomes. Only one harbored the Epstein-Barr virus. Among 13 patients with a median follow-up of 3 years, local recurrence occurred in 6, metastasis in 6, and 3 died of disease. CONCLUSIONS: Follicular dendritic cell sarcoma exhibits distinctive histologic features that permit its presumptive recognition, but a firm diagnosis requires confirmation with special studies. Because it has a significant recurrent and metastatic potential (the latter risk having been previously underestimated), it should be viewed as an intermediate grade malignancy. An intraabdominal location is associated with a particularly aggressive clinical course.

Adolescent

T- and T/natural killer-cell lymphomas of the salivary gland: a clinicopathologic, immunohistochemical and molecular study of six cases.

Primary salivary gland lymphomas are almost always of B lineage, with most being represented by low grade B-cell lymphoma of mucosa-associated lymphoid tissue. This study characterizes the rare non-B-cell lymphomas of the salivary gland based on an analysis of six cases. All patients were men, with a mean age of 53.5 years. They presented with submandibular or parotid mass, which on histological examination showed extensive interstitial infiltration by small, medium-sized, or large lymphoid cells. There was prominent invasion and expansion of the ducts and acini in five cases. Angioinvasion was evident in two cases. Three cases were of T lineage and were CD56 negative; one of these cases expressed CD30. Three cases showed an immunophenotype of CD2+ CD3(f)- CD3(p)+ CD56+, consistent with T/natural killer (NK) cell lymphoma. In situ hybridization for Epstein-Barr virus (EBV)-encoded early nuclear RNA (EBER) showed positive reaction exclusively in the three CD56+ cases. Clonal T-cell populations were shown in two CD56-negative cases by polymerase chain reaction on paraffin sections using primers for the T-cell-receptor (TCR) gamma-chain gene, but not in the other four cases (the three CD56+ cases and one CD56- case). Four patients (two CD56+ and two CD56-) died within 3 years, and two were disease free at 4 and 1.5 years, respectively. This study shows that salivary gland T- or T/NK-cell lymphomas cannot be reliably distinguished from B-cell lymphomas on morphological grounds alone, because both can show prominent lymphoepithelial lesions. It appears that T/NK-cell lymphomas, which are often extranodal in localization and strongly associated with Epstein-Barr virus (EBV), show a predilection to involve the salivary glands as well.

Aged

Mammary myofibroblastoma with leiomyomatous differentiation.

An unusual example of mammary myofibroblastoma in a 36-year-old woman was reported. The central portion resembled mammary myofibroblastoma or solitary fibrous tumor of other sites and showed reactivity for CD34 and muscle-specific actin, with few cells staining for desmin. The peripheral portion resembled leiomyoma and showed strong reactivity for actin and desmin but only focal staining for CD34. We interpret this tumor as mammary myofibroblastoma showing frank peripheral leiomyomatous differentiation. Although closely related to solitary fibrous tumor, mammary myofibroblastoma appears slightly different because of its consistent slant toward myoid differentiation in the form of actin and variable desmin reactivity as opposed to the rare and sparse immunohistochemical expression of myoid features by solitary fibrous tumors of other sites. This case demonstrates this phenomenon carried to an extreme, a feature not previously documented in mammary myofibroblastoma. It is of interest to note the modulation of the antigenic profile with the differentiation process, that is, loss of CD34 and gain of desmin accompanying the myoid differentiation.

Adult

Cytokeratin 20 immunoreactivity distinguishes Merkel cell (primary cutaneous neuroendocrine) carcinomas and salivary gland small cell carcinomas from small cell carcinomas of various sites.

Cytokeratin 20 (CK20) is a low-molecular-weight cytokeratin (CK) that shows restricted expression in the gastrointestinal epithelium, urothelium, and Merkel cell. Recent studies have suggested that since Merkel cell (primary cutaneous neuroendocrine) carcinomas are consistently CK20-positive, this feature may help to distinguish it from pulmonary small cell carcinomas. However, only limited numbers of these tumors have been studied, and the pattern of CK20 expression in other small cell carcinomas has not been established. Therefore, we studied CK20 expression in small cell carcinomas from a wide variety of sites. Immunohistochemical study was performed on paraffin sections using CK20 antibody, coupled with antigen retrieval by pressure cooking in citrate buffer. The cases included 34 Merkel cell carcinomas and 89 small cell carcinomas from various sites (pulmonary, 37; gastrointestinal tract, nine; pharynx and tongue, two; sinonasal tract, three; salivary gland, five; larynx, nine; breast, two; thymus, three; uterine cervix and corpus, 12, prostate, three; urinary bladder, two; kidney, one; pancreas, one). In addition, all cases were immunostained with pan-CK (MNF-116) and low-molecular-weight CK (CAM5.2) antibodies to ascertain their epithelial nature. With the exception of one case, all Merkel cell carcinomas were CK20-positive; and 30 of the 33 cases showed a punctate pattern. Almost 100% of tumor cells were positive, except for two cases that showed staining of 10% and 30% of tumor cells, respectively. Among the other small cell carcinomas, only five cases were CK20-positive, including one of 37 pulmonary (40% cells positive in punctate pattern), one of 11 cervical (10% cells positive), and three of five salivary gland (100% cells positive). We conclude that CK20-positivity in a small cell carcinoma of uncertain origin strongly predicts a diagnosis of Merkel cell carcinoma, especially if the majority of tumor cells are positive. A negative CK20 reaction can practically rule out Merkel cell carcinoma, provided that an effective antigen retrieval technique is used and appropriate staining is obtained with other cytokeratin antibodies. The frequent CK20 positivity observed in salivary gland small cell carcinomas in this series suggests that at least some of them may be more closely related biologically to Merkel cell carcinoma than to pulmonary-type small cell carcinoma. This may explain why they are far less clinically aggressive than other small cell carcinomas.

Biomarkers, Tumor

Prevalence of asthma and allergy in Hong Kong schoolchildren: an ISAAC study.

Asthma and allergic disease in children is increasing in many Western countries but such trend has not been well-defined in Chinese populations. This paper aims to determine the prevalence of asthma and allergic disease in Hong Kong schoolchildren and compare it with previous data to identify a changing trend. We studied 4,665 schoolchildren aged 13-14 yrs using the International Study of Asthma and Allergy in Childhood (ISAAC) protocol to determine prevalence rates for asthma, wheeze, respiratory symptoms, rhinitis and eczema in 1994-1995. Additional questions on education levels of the parents and smoking status were also asked. Concordance between responses to the written and video questionnaires was good (76% for wheeze ever, 80% for current wheeze). Prevalence rates for asthma ever, wheeze ever, and current wheeze were 11, 20 and 12%, respectively, and were greater in boys (p < 0.05). Rhinitis affected slightly over half of the subjects (52%), and eczema was reported by a sixth (15%), whilst current rhinitis and current eczema were present in 44% and 3.6% of children, respectively. In multiple logistic regression: odds ratio male sex (OR) 1.47; (95% confidence interval (95% CI) 1.15-1.86); current rhinitis (OR 3.00; 95% CI 2.36-3.81); current eczema (OR 2.34; 95% CI 1.40-3.93); and active smoking (OR 2.00; 95% CI 1.38-2.89) were associated with current wheeze; whilst severe wheezing attack was associated with: current rhinitis (OR 2.72; 95% CI 1.47-5.02); current eczema (OR 6.13; 95% CI 2.82-13.33); and active smoking (OR 4.62; 95% CI 2.43-8.76). Age, parental education and passive smoking were not important factors. When compared to previous epidemiological data obtained in 1992, the prevalence rates for asthma ever and wheeze ever had increased by 71 and 255%, respectively, in Hong Kong schoolchildren. The severity of asthma and respiratory symptoms showed a similar increasing trend. Further studies should aim to identify the role of the environment in the pathogenesis of asthma.

Adolescent

Lipoadenoma of the parotid gland with probable striated duct differentiation.

We report an example of lipoadenoma of the parotid gland, a previously undescribed tumor of the salivary gland. It is a well-circumscribed tumor comprising an intimate admixture of mature fat cells and branching narrow tubules. The tubules were elongated and had small or absent lumina, resulting in a remarkable Sertoliform pattern. They were lined by columnar cells, which were supported by a basal cell layer. The latter cells lacked evidence of myoepithelial differentiation but were best highlighted by immunostaining for high molecular-weight cytokeratin (34 beta E12). Comparison with the normal salivary gland components showed the greatest homology of the neoplastic tubules with the striated duct, which normally has an incomplete basal cell layer. The latter phenomenon is under-recognized, with some current textbooks still describing the presence of a single cell type only in the striated duct of the salivary gland.

Adenoma

Minimum graft volume for successful adult-to-adult living donor liver transplantation for fulminant hepatic failure.

The major limitation of adult-to-adult living donor liver transplantation is the adequacy of the size of the graft that can be safely harvested from the donor. The present report describes a 22-year-old woman with stage 4 hepatic coma due to fulminant hepatic failure who was successfully treated using a small-for-size left lobe graft from her father. The graft weight was 0.6% of the recipient's body weight, or 25% of her ideal liver weight. Avoidance of warm ischemia, short cold ischemic time, and early treatment of rejection are important elements in optimizing small-for-size graft function. Since the left lobe represents 23-36% of the total liver volume of an adult, it is possible, in most cases, to harvest a left lobe graft of adequate size from a donor of similar size as the recipient.

Adult

Aggressive T/natural killer cell lymphoma presenting as testicular tumor.

BACKGROUND: Nonnasal CD56+ T/natural killer (NK) cell lymphomas with morphologic and immunogenetic features similar to those of the distinctive nasal T/NK cell lymphoma are uncommon and have been characterized only recently. They show predominantly extranodal presentation, high stage disease, a highly aggressive course, strong association with Epstein-Barr virus (EBV), and lack of T cell receptor gene rearrangement. Only one previously reported case had a testicular presentation, although the testis is not uncommonly involved during the course of disease in both nasal and nonnasal T/NK cell lymphomas. METHODS: Three patients with T/NK cell lymphoma who presented initially with a testicular mass are reported. RESULTS: The three patients underwent orchidectomy for testicular tumor. Histologically, the testes showed diffuse dense infiltration of medium-sized or large lymphoma cells. Antiocentric growth and necrosis were prominent in two cases. The lymphoma had the following immunophenotype: CD2+ CD3 epsilon+ CD56+ compatible with T/NK cell lymphoma; two lacked staining with Leu4 (CD3), and one had weak staining. With immunohistochemical preparations, it was noted that the rete testis stained consistently for CD56, and the Leydig cells and Sertoli cells showed patchy staining. The neoplastic cells harbored EBV, as demonstrated by in-situ hybridization. Additional sites of disease were detected at the time of the diagnosis in one patient (nose) or appeared soon afterwards in all three patients (skin or gastrointestinal tract). All three patients died within 5 months. CONCLUSIONS: This study confirms that testicular CD56+ T/NK cell lymphoma tends to disseminate early, pursues an aggressive course, and is strongly associated with EBV. CD56 recognizes the neural cell adhesion molecule (NCAM), which exhibits homophilic binding properties. The expression of CD56 in the normal testicular constituents can perhaps explain the tendency for T/NK cell lymphoma to localize in this organ.

Aged

Pituitary adenoma presenting as sinonasal tumor: pitfalls in diagnosis.

Pituitary adenomas may cause significant difficulties in histological diagnosis when presenting in unusual sites either as extension from an intrasellar lesion or as ectopic tumor. Three such cases, involving the sinonasal tract are described herein, and the differential diagnoses are discussed. Two of them were invasive intrasellar macroadenomas that presented as unilateral nasal polyp, and one was an ectopic pituitary adenoma involving the sphenoid sinus. There was notable cellular atypia in two cases, with nuclear pleomorphism, giant cells, chromatin clumping, and distinct nucleoli, leading to serious consideration of the possibility of poorly differentiated carcinoma. In none of the cases was the diagnosis of pituitary adenoma suspected clinically. The clues to diagnosis were an endocrine growth pattern comprising tumor cells arranged in packets, ribbons, or rosettes, with prominent delicate vascularized stroma; a high index of suspicion; and immunohistochemical showing of neuroendocrine markers and pituitary hormones in the tumor cells. A correct diagnosis is important because in contrast to neuroendocrine carcinoma as a whole or to poorly differentiated carcinoma, pituitary neoplasms have a much more favorable prognosis and a low metastatic potential.

Adenoma

A study of the possible etiologic association of Epstein-Barr virus with reactive hemophagocytic syndrome in Hong Kong Chinese.

The herpes group of viruses, particularly Epstein-Barr virus (EBV), has frequently been implicated in the causation of reactive hemophagocytic syndrome (RHS) in the Western populations. EBV has also been implicated in the rare fulminant form of RHS occurring in Oriental children. However, our previous adult-predominant study indicated little clinical and serological evidence of EBV infection in patients with RHS in Hong Kong. In the present study, we further examined this issue using a more sensitive and specific technique for the demonstration of EBV, ie, in situ hybridization for EBV encoded RNA (EBER). The 43 Chinese patients studied were mostly adults with a mean age of 44 years, and a male to female ratio of 1.5:1. About two-thirds (28) of patients had associated malignant lymphoma at the time of diagnosis. Five patients had documented infection (typhoid fever 2; systemic candidiasis 1; adenovirus pneumonia 1; viral encephalitis 1), and two had systemic lupus erythematosus. EBER signals were detected in only 11 cases (25.6%). All positive cases were associated with malignant lymphoma, and the positive signals were exclusively localized to the lymphoma cells but not in the histiocytes. On comparing the results (11 of 28 cases positive; 39.3%) with our previous data on EBER-expression in malignant lymphomas in Hong Kong, no significant difference is observed in the frequency of EBV-positivity between the two groups of lymphomas. Thus, a definite pathogenetic link between EBV and lymphoma-associated RHS cannot be established. However, the overrepresentation of T and T/NK lineage lymphoma in this sample of lymphoma-associated with RHS (61%) versus nonselected cases of lymphomas (31%) suggests that it is the T and T/NK cell origin of the lymphoma rather than the EBV positivity that predisposes to RHS. Notwithstanding the previous findings, EBER in situ hybridization may still serve as a useful adjunct in the investigation of patients with RHS, because the presence of EBER-positive cells should raise a strong suspicion of an underlying malignant lymphoma.

Adolescent

Fluoride pharmacokinetics and changes in lumbar spine and hip bone mineral density.

Debate about the use of fluoride for the treatment of vertebral osteoporosis has centered not only on whether fluoride treatment decreases vertebral fractures, but also the interindividual vertebral bone mineral density (BMD) response, the potential for nonvertebral fractures, as well as side effects and tolerability. These effects may be dose dependent and, in this study, we examine the pharmacokinetics of sodium monofluorophosphate (MFP) in osteoporotic patients and relate this to changes in BMD. Plasma fluoride absorption curves were measured from 0 to 6 h after ingestion of MFP at baseline and during long-term dosing in 21 patients with vertebral osteoporosis (T scores < or = 2). BMD was measured at baseline and at 12 months at the lumbar spine (LS), femoral neck (FN), trochanter, and Ward's triangle. We found that fluoride elimination was inversely related to creatinine clearance. LS BMD increased from a median of 0.77 g/cm2 (range 0.69 to 0.99) at baseline to 0.88 g/cm2 (0.75 to 1.13) (p < 0.001) after 12 months. This equates to a median increase of 12% (range -1.2 to 37). Median femoral neck BMD decreased from 0.75 g/cm2 (0.62 to 0.94) at baseline to 0.69 g/cm2 (0.62 to 0.92) (p = 0.13) after 12 months. This equates to a decrease of -2% (-19 to 10). BMD at the other hip sites also decreased slightly. Changes in LS and FN BMD were not significantly related (r = 0.28, p = 0.29). The various pharmacokinetic parameters measured were not related to changes in LS BMD; however, there was an inverse relationship between trough fluoride concentration during long-term dosing and change in FN BMD. Further studies are required to see if this relationship can be used to monitor osteoporotic patients treated with fluoride and prevent significant decreases in FN BMD and possibly fractures at this site.

Adult

T-cell form of chronic lymphocytic leukaemia: a reaffirmation of its existence.

Early in the 1980s three categories of T-cell chronic lymphocytic leukaemia were recognized: CD4+ CD8- knobby type, CD4- CD8+ azurophilic type and CD4+ CD8- adult T-cell leukaemia (ATL) type. Both azurophilic and ATL types were later shown to be distinctive disorders, whereas the knobby type has been largely neglected and even considered non-existent by some authors. In this report we describe two patients with leukaemia of CD3+ CD4+ CD8- post-thymic T lymphocytes presenting with marked lymphocytosis, generalized lymphadenopathy and hepatosplenomegaly. We believe that CLL of the post-thymic T-lymphocytes is a distinct entity, and merits a separate designation from other T-cell leukaemias.

Adult

Paucicellular variant of anaplastic thyroid carcinoma. A mimic of Reidel's thyroiditis.

Anaplastic thyroid carcinomas usually pose no problems in histologic diagnosis because of the obvious invasive growth, high cellularity, and frank anaplasia. Two cases of a variant of anaplastic thyroid carcinoma with peculiar gross and histologic features closely mimicking those of Riedel's thyroiditis are described in this report. The clinical features were no different from those of the usual anaplastic thyroid carcinomas: occurrence in elderly subjects, presentation with rapidly enlarging neck mass associated with compression symptoms, and rapidly fatal outcome. The tumors were infiltrative, hard, fibrotic masses that partly or completely replaced one lobe of the thyroid, and extended to perithyroid tissues. Histologically, they were predominated by acellular fibrous or infarcted tissue with central dystrophic calcification, as well as hypocellular foci comprising mildly atypical spindle cells intermingled with collagen and small lymphocytes. Both cases showed permeation and plugging of the arteries by tumor. Lymph node metastasis was documented in one case. The spindle cells were positive for epithelial membrane antigen in both cases, and cytokeratin in one. The qualifying term "paucicellular variant" accurately describes this uncommon morphologic variant of anaplastic thyroid carcinoma. It is important to recognize this variant so as not to mistaken it for Riedel's thyroiditis, which is a reactive condition with a very favorable prognosis. The distinguishing features are as follows: presence of infarction, atypical cells in at least some areas, atypical spindle cells obliterating large blood vessels, and immunoreactivity for epithelial markers.

Aged

Tubular adenosis of the breast. A distinctive benign lesion mimicking invasive carcinoma.

Tubular adenosis, a term first coined by Oberman, is an uncommon benign lesion of the breast that may mimic invasive carcinoma. There is no formal description of this condition in the literature. We report the findings on six specimens from five patients (one with bilateral disease), including three that showed cancerization by intraductal carcinoma (DCIS). The ages of the patients ranged from 40 to 82 years. One patient presented with a 3-cm breast mass, and the others were found in specimens resected for infiltrating ductal carcinoma (two specimens) or DCIS (three specimens). The histologic hallmark of tubular adenosis was haphazard proliferation of elongated tubules that were noncrowded, narrow, and sometimes branching. There was no lobular arrangement or, at most, vague lobular grouping, with some tubules often extending into the fat. The tubules contained basophilic or granular eosinophilic secretion. The stroma was sclerotic to edematous. The tubules were lined by bland-looking ductal cells and were surrounded by an intact myoepithelial layer, a phenomenon well highlighted by immunostaining for muscle-specific actin (HHF-35) or S-100 protein. In three specimens, the tubular adenosis was cancerized by noncomedo DCIS, producing a pattern strongly mimicking infiltrating carcinoma; the in situ nature of the carcinoma was confirmed by actin immunoreactivity in the residual myoepithelium as well as by the presence of architecturally similar tubular adenosis in the vicinity. Tubular adenosis shows an infiltrative growth similar to microglandular adenosis and adenomyoepithelial adenosis, but it differs from them by the interdigitating tubular configuration and also differs from microglandular adenosis by the presence of myoepithelium. Tubular adenosis can be distinguished from sclerosing adenosis by the lack of obvious lobular architecture or whorled arrangement and wider separation of the tubules. Tubular adenosis appears to be a benign lesion per se, but whether it has premalignant potential remains to be determined. The importance of recognizing this entity lies in its being potentially mistaken for invasive carcinoma, especially at intraoperative frozen section or when the lesion is cancerized by DCIS.

Adult

Report of the Workshop on Nasal and Related Extranodal Angiocentric T/Natural Killer Cell Lymphomas. Definitions, differential diagnosis, and epidemiology.

A workshop jointly sponsored by the University of Hong Kong and the Society for Hematopathology explored the definition, differential diagnosis, and epidemiology of angiocentric lymphomas presenting in the nose and other extranodal sites. The participants concluded that nasal T/natural killer (NK) cell lymphoma is a distinct clinicopathologic entity highly associated with Epstein-Barr virus (EBV). In situ hybridization for EBV an be very valuable in early diagnosis, especially if tissue is sparse. The cytologic spectrum is broad, ranging from small or medium-sized cells to large transformed cells. Histologic progression often occurs with time. Necrosis is nearly always present, and angioinvasion by tumor cells is seen in most cases. Nasal T/NK cell lymphoma has a characteristic immunophenotype: CD2-positive, CD56-positive, but usually negative for surface CD3. Cytoplasmic CD3 can be detected in paraffin sections. Clonal T-cell receptor gene rearrangement is not found. Tumors with an identical phenotype and genotype occur in other extranodal sites, most commonly in the skin, subcutis, and gastrointestinal tract, and should be referred to as nasal-type T/NK cell lymphomas. The differential diagnosis includes lymphomatoid granulomatosis, blastic or monomorphic NK cell lymphoma/leukemia, CD56-positive peripheral T-cell lymphoma, and enteropathy-associated T-cell lymphoma.

Diagnosis, Differential