The impact of IgG-4-ROD on the diagnosis of orbital tumors: A retrospective analysis.

This study was to determine the prevalence of immunoglobulin G4 (IgG4)-related orbital disease (IgG4-ROD) among patients who have previously undergone biopsy and were diagnosed to have idiopathic orbital inflammatory disease (IOID) or orbital lymphoproliferative disease (OLD), namely, lymphoma and benign reactive lymphoid hyperplasia (BRLH). This is a retrospective cross-sectional study. The charts and slides of all patients who underwent biopsies and were histopathologically diagnosed to have either IOID or OLD were reviewed. Demographics, clinical features, initial histopathological diagnoses, treatment received, and final outcome were noted. Using the diagnostic criteria for diagnosis for IgG4 disease, those cases that would classify as "possible IgG4-related disease (IgG4-RD)" were reviewed, reclassified, and reassigned a diagnosis of IgG4-ROD. We reviewed 105 patients' clinical charts. Of these 105 patients, upon reviewing the histopathology, 18 (17.15%) patients were found to fit the diagnostic criteria for possible IgG4-ROD. Of these 18 patients who were now reassigned the diagnosis of IgG4-ROD, the most common previous histopathological diagnosis was found to be IOID, for eight patients (44%), then BRLH, which was noted in five patients (27.8%), followed by lymphoma, which was noted in two patients (11.1%). Previously diagnosed cases of IOID and OLD were found to fulfill the criteria for IgG4-ROD. Given the advent of recent diagnostic and histopathological techniques, all cases of suspected IOID and OLD should be screened for IgG4-ROD and all previously diagnosed cases must be closely followed up, given the systemic implication of IgG4-RD. Histopathological reassessment of previously diagnosed cases may be considered.

Borrelial Lymphocytoma in Adult Patients.

BACKGROUND: Information on the course and outcome of borrelial lymphocytoma (BL) is limited. METHODS: The study comprised 144 adult patients (75 female, 69 male; median age, 49 years) who had BL diagnosed at a single center between 1986 and 2014 and were followed up for 1 year. RESULTS: BL was located on the breast in 106 patients (73.6%), on the ear lobe in 27 (18.8%), and elsewhere in 11 (7.6%). The median duration of BL before diagnosis was 27 days (interquartile range [IQR], 9-68 days). Concomitant erythema migrans was registered in 104 of 144 patients (72.2%); other objective manifestations of Lyme borreliosis (LB) were present in 11 (7.6%). Immunoglobulin M and/or G borrelial serum antibodies were present in 72 patients (50%). Borreliae were isolated from BL lesions in 14 of 42 patients (33.3%) who had not received antibiotics before skin biopsy. Of 13 typed Borrelia strains, 11 were B. afzelii, 1 was B. garinii, and 1 was B. bissettii The median duration of BL after starting antibiotic treatment was 21 days ([IQR], 10-30 days); the average duration was longer in patients who were older, had longer BL duration before treatment, or had signs of disseminated LB. Treatment failure occurred in 14 of 144 patients (9.7%). Patients with signs or symptoms of disseminated LB before treatment had nearly 4 times higher odds of treatment failure (95% confidence interval, 1.22-13.07) than those without such symptoms. All patients with treatment failure had uneventful outcome after retreatment. CONCLUSIONS: BL is a rare manifestation of early localized LB. Fourteen-day antibiotic treatment, as used for erythema migrans, is effective.

Lymphoid Interstitial Pneumonia and Other Benign Lymphoid Disorders.

Benign pulmonary lymphoid disorders include a variety of rare lymphoid abnormalities characterized by a polyclonal lymphoid infiltrate with differing histopathologic patterns and clinicoradiologic features that may overlap. Histological examination is essential to reach a correct diagnosis and to exclude alternative causes, although this task can at times prove difficult. Further studies and clinical trials are needed to provide additional insights on pathogenesis and to guide the therapeutic management of these disorders. The purpose of this article is to review the histopathological, epidemiological, and clinicoradiologic features of several benign pulmonary lymphoid disorders, including lymphoid interstitial pneumonia, follicular bronchiolitis, nodular lymphoid hyperplasia (pulmonary pseudolymphoma), inflammatory pseudotumor, immunoglobulin G4-related disease, Castleman disease, posttransplantation lymphoproliferative disease, and drug-induced lymphoid disorders.

Prevalence and risk factors for adenomas in the ileal pouch and the afferent loop after restorative proctocolectomy for patients with familial adenomatous polyposis.

BACKGROUND: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has become the treatment of choice in familial adenomatous polyposis (FAP) to prevent the risk of colorectal cancer. However, it currently is recognized that adenomas may develop in the ileal pouch. The risk of adenoma occurring in the afferent ileal loop above the pouch is less clearly identified. This study aimed to evaluate the difference in prevalence of adenomas between the ileal pouch and the afferent ileum after IPAA in FAP. METHODS: The study analyzed 442 endoscopies performed between 2003 and 2008 for 139 FAP patients. The patients had undergone an IPAA in 118 cases, an ileorectal anastomosis in 13 cases, or an ileostomy in 8 cases. RESULTS: Among the 118 IPAA patients, 57 (48.3 %) had pouch adenomas a median of 15 years after surgery. The risk factors for pouch adenomas were delay since pouch construction [odds ratio (OR), 1.11; p = 0.016] and presence of advanced duodenal adenomas (OR, 4.35; p = 0.011). Seven patients had pouch adenomas with high-grade dysplasia. Only nine patients had afferent ileal loop adenomas (6.5 %). The only significant risk factor for ileal adenomas was the presence of pouch adenomas (OR, 2.16; p = 0.007). CONCLUSION: After restorative proctocolectomy in FAP, adenoma recurrence is frequent in the pouch, with a higher risk for patients with advanced duodenal adenomas and an increasing risk over time, whereas adenomas are rarely found in the afferent ileal loop. This finding may help to propose redo ileal pouch anal anastomosis if required.

Actinic reticuloid--photosensitivity or pseudolymphoma?--A review.

Actinic reticuloid (AR) or chronic actinic dermatitis is considered a sunlight-induced pseudolymphoma (PSL) on light exposed areas of the skin, which primarily affects elderly males. The disease is a severe, chronic photosensitive dermatosis, first described by Ive et al. in 1969. PSL is a group of non-cancerous lymphocytic skin disorders that simulate malignant lymphomas, but the changes usually spontaneously regress. The clinical appearance of Actinic reticuloid is variable, usually characterized by an eczematous, pruritic eruption, predominantly present on the head and neck, or other sun exposed areas, but can involve any area of the body. Thereby, crucial characteristic is photosensitivity, where at action spectrum involves UVB, UVA and visible light beyond 400 nm. The disease is considered as PSL which histologically resembles lymphoma with immunohistochemical analysis of the cutaneous infiltrate revealing presence of activated T cells, numerous histiocytes, macrophages and B cells. Moreover, the development of malignant (non-cutaneous) T cell lymphoma in the course of AR has been reported. As the disease has chronic character, it requires significant changes in the patient's lifestyle and avoidance of provoking factors such as contact allergens or sources of intense light. Thus AR should be considered in every patient who presents with persistent, unclear, erythematous skin changes on the face and neck that are related to sun exposure.

Lymphocytic Myocarditis and Cardiogenic Shock in Hawai'i: A Case Series.

Lymphocytic myocarditis is an inflammatory disease of the heart that may present in a myriad of fashions ranging from mild febrile illness to florid myocarditis and cardiogenic shock. Given its nonspecific clinical presentation, the diagnosis of lymphocytic myocarditis is often challenging. The authors describe four cases of lymphocytic myocarditis in young women who presented with cardiogenic shock. Two patients survived and two died. This presentation has not been seen previously in Hawai'i and the public awareness of this condition is critical. Early diagnosis and the prompt initiation of biventricular mechanical circulatory support appear to have been critical in improving patient survival.

Expression and clinical significance of ubiquitin­specific­processing protease 34 in diffuse large B­cell lymphoma.

Ubiquitin­specific­processing protease 34 (USP34) is a deubiquitinase that is involved in the pathogenesis of various cancers. Its roles in diffuse large B­cell lymphoma (DLBCL) are unknown. The present study aimed to determine the level of USP34 expression and to explore its association with clinicopathological features and prognosis in patients with DLBCL; a total of 30 cases of reactive lymphoid hyperplasia and 131 cases of DLBCL were included in this study. The level of USP34 expression was examined by immunohistochemistry (IHC), and correlations between USP34 expression and clinicopathological features and prognosis were analyzed. In addition, mutations, expression and clinical significance of USP34 in DLBCL were evaluated using data from The Cancer Genome Atlas (TCGA). USP34 expression was significantly higher in DLBCL compared with expression in reactive lymphoid hyperplasia. In DLBCL, overexpression of USP34 was associated with older age, germinal center B cell­like (GCB) subtype, multiple extranodal involvements and higher International Prognostic Index (IPI) scores. No significant association was identified between USP34 protein level and patient survival. In the TCGA dataset, low USP34 mRNA expression was demonstrated to be associated with a poor disease­free survival (DFS), but not with overall survival (OS) in patients with DLBCL. In conclusion, high expression of USP34 protein in DLBCL was associated with older age, GCB subtype, multiple extranodal involvement and high IPI scores of DLBCL. USP34 may be a valuable marker for the assessment of patients with DLBCL, and further studies are needed to clarify USP34 expression on DLBCLs.

Lymphoproliferative diseases of the ocular adnexa in Korea.

OBJECTIVES: To evaluate the clinical features, treatments, and outcomes of patients with ocular lymphoproliferative disease classified according to the World Health Organization classification and to determine prognostic factors of this disease in South Korea. METHODS: Between March 1, 1995, and December 31, 2005, 128 cases of patients with ocular lymphoid tumors treated at the Samsung Medical Center were retrospectively reviewed. RESULTS: The mean patient age was 46.3 years (range, 1-87 years). The major histopathologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 96 patients (75.0%), lymphoid hyperplasia in 11 (8.6%), diffuse large B-cell lymphoma in 6 (4.7%), and mantle cell lymphoma in 4 (3.1%). Ocular lymphoproliferative lesions were located in the conjunctiva (53 patients), the eyelid (33 patients), and the orbit (42 patients). Twenty patients had tumor relapses (15.6%), and 9 died of lymphoma during follow-up (7.0%). Regarding the analysis of prognostic factors, most patients with MALT lymphoma evidenced local disease, required local treatment, and exhibited a superior prognosis. CONCLUSIONS: Lymphomas of the MALT type constitute most ocular adnexal lymphoproliferative diseases and occur more frequently in South Korea than in Western countries. Patients with MALT lymphoma have favorable outcomes compared with patients with other types of lymphoma.

High incidence of autoimmune disease in Japanese patients with ocular adnexal reactive lymphoid hyperplasia.

PURPOSE: To determine the incidence of autoimmune disease in Japanese patients with ocular adnexal lymphoid proliferations. DESIGN: Case series study. METHODS: The authors investigated the incidence of autoimmune disease in 88 patients with primary ocular adnexal lymphoid proliferations. Southern blot analysis was used to determine the presence of B-cell clonality in reactive lymphoid hyperplasia (RLH) associated with autoimmune disease. RESULTS: Histopathologic analysis indicated that 15 (17%) patients had RLH, 62 (70%) patients had mucosa-associated lymphoid tissue lymphoma (MALToma), and 11 (13%) patients had primary lymphomas. The incidence of autoimmune disease was seven (47%) of 15 patients with RLH, two (3%) of 62 patients with MALToma, and zero (0%) of 11 patients with primary lymphoma. B-cell clonality was detected in one (14%) of seven RLH patients with autoimmune disease. CONCLUSIONS: Ocular adnexal RLH with or without B-cell clonality is highly associated with autoimmune disease.

Benign reactive lymphoid hyperplasia of the conjunctiva in childhood.

BACKGROUND/AIM: Our aim is to the report the clinical and histopathological features of benign reactive lymphoid hyperplasia (BRLH) of the conjunctiva in children and the outcomes of treatment. METHODS: A retrospective chart review was performed for children aged 0-18 years, diagnosed with conjunctival BRLH from January 2000 to December 2013 at two large ophthalmology hospitals in the Middle East. Data were collected on patient demographics, features of the lesions, the site of the lesion, location, adnexal involvement, lymph nodes involvement, local spread, histopathology and molecular genetic studies of the cases (if available), outcomes of treatment and recurrence. RESULTS: There were 24 patients with lymphoid lesions classified as conjunctival BRLH during the 12-year period evaluated in this study. The mean age at diagnosis was 11.6 years. Twenty-three patients were males (96%). Systemic medical history included three patients with bronchial asthma, one patient with Down's syndrome, one patient with generalised skeletal malformation and one patient with gastritis. The initial uncorrected visual acuity was 20/30 or better in 93.5% of the eyes. At presentation, the tumour was unilateral in 12 cases (50%). The conjunctival mass was located on the bulbar conjunctiva in all cases. The mass was present nasally in 96% of lesions. No cases (that were tested) had an infectious aetiology. PCR demonstrated monoclonality suggestive of lymphoma in two cases; however, this did not alter the final diagnosis as BRLH per histopathological criteria and clinical course, CONCLUSIONS: All investigated cases of paediatric conjunctival BRLH had a benign clinical course with no local or systemic dissemination and a male predominance. Recurrence was rare, and in our cohort, it was not associated with malignant transformation.

Reactive lymphoid hyperplasia of the liver in a patient with colon cancer: report of two cases.

BACKGROUND: Reactive lymphoid hyperplasia (RLH) of the liver is very rarely reported, and we encountered two cases of RLH of the liver in a patient with colon cancer. CASE PRESENTATION: In the first case, a 77-year-old woman was admitted for the surgical removal of a ascending colon cancer. A hepatic tumor in the left lobe was concurrently revealed by computed tomography (CT), and magnetic resonance imaging (MRI). The appearance suggested liver metastasis. Right hemicolectomy and partial hepatectomy were performed. On histopathological examination, lymphoid follicles with germinal centers were seen in the tumor-like lesion, and remarkable lymphoid infiltration with germinal centers was seen in the portal area around the nodule. Immunohistochemical studies revealed polyclonality of infiltrating lymphocyte. Consequently, this nodular lesion was diagnosed as RLH of the liver. In the second case, a 64-year-old woman who had a radical right hemicolectomy for stage II ascending colon cancer 10 years ago was admitted with dysuria. A hepatic tumor in the left lobe was concurrently revealed by CT and MRI, suggesting hepatocellular carcinoma. A left lateral segmentectomy was performed. Microscopically, this lesion revealed the almost same findings as the first case, so this nodular lesion was diagnosed as RLH of the liver. CONCLUSION: Our two cases were the first report of RLH of the liver accompanying colon cancer. Because there are a very few cases, so it is not clear whether the malignancies were involved in the onset of RLH. But we believe that new factors involved in the onset mechanism of RLH may be identified by carefully monitoring the clinical course of our two patients.

Lymphoproliferative disorders in Costa Rica and simian virus 40.

BACKGROUND AND OBJECTIVES: Simian virus 40 (SV40) is an oncogenic DNA virus implicated in some human malignancies, including lymphomas. In the present masked case-control study, we investigated the prevalence of SV40 sequences and the expression of the viral oncoprotein, large tumor antigen (T-ag), in lymphomas and control specimens from patients negative for the human immunodeficiency virus in Costa Rica. DESIGN AND METHODS: Coded specimens were anlyzed by polymerase chain reaction for SV40 and Epstein-Barr virus (EBV). SV40 sequences were confirmed by Southern blot and DNA sequence analysis. Immunohistochemistry was used to detect the expression of SV40 T-ag in coded samples and to immunophenotype the lymphomas. RESULTS: When samples were decoded, SV40 DNA sequences were detected significantly more often in lymphomas than in control samples (30/125, 24% vs. 0/91, 0%; p=0.001). SV40 DNA was detected in 26% and 10% of non-Hodgkin's and Hodgkin's lymphomas, respectively. EBV DNA was detected in 10% of lymphomas and 33% of control specimens. None of the lymphomas was positive for both SV40 and EBV. Expression of SV40 T-ag was detected in 64% of B-cell lymphomas that contained T-ag DNA sequences and in none of the samples negative for viral DNA. Not all cells in a positive tumor expressed T-ag and the reactions were relatively low intensity. A germinal center B-cell-like profile was frequently associated with SV40-positive lymphomas. Of note, 20% of patients with SV40-related lymphomas were born in the 1970s and 1980s. INTERPRETATION AND CONCLUSIONS: These results indicate that SV40 is significantly associated with some B-cell neoplasms in Costa Rica today.

Borrelial Lymphocytoma in Children.

BACKGROUND: The aim of this study was to investigate demographic features, clinical characteristics, laboratory findings and posttreatment course of the disease in children with borrelial lymphocytoma (BL). METHODS: Between 2008 and 2014, we prospectively studied 33 children younger than 15 years with untreated BL. Data on demographic and clinical features were collected by means of a questionnaire. Serological testing and Lyme borrelia blood cultures were performed. All patients were treated with recommended antibiotics. Patients were followed up at least 3 months after inclusion into the study. RESULTS: Twenty-two boys and 11 girls, aged 2-13 (median, 5.5) years, fulfilled the inclusion criteria. A tick bite at the site of BL was recalled by 30%. The median incubation period was 10.5 (range, 1-38) days. The median duration of BL before the initial examination was 10 (range, 0-270) days. In 88% of patients, BL was localized on ear lobe. The color/shape of BL was more often red (73%) and puffy (91%). Median size was 1.5 (range, 0.5-3) cm. The initial disease was mild in 82%. Associated symptoms were reported in 36% of patients. Concomitant solitary erythema migrans and meningitis were detected in 9% and 3% of patients, respectively. Serum borrelial antibodies were present in 40% of patients. In 7%, Borrelia afzelii was isolated from blood. Posttreatment course of the disease revealed the median duration of BL and systemic symptoms for 16 (range, 2-46) and 15 (range, 3-40) days, respectively. CONCLUSIONS: BL in children, treated with recommended antibiotics, is a mild disease with a good prognosis.

Tumor profile of novel p53 heterozygous Tg.AC (v-Ha-ras) bitransgenic mice treated with benzo(a)pyrene and fed dietary N-acetyl-L-cysteine (NAC).

We designed a novel short-term bitransgenic model to better characterize the effects of benzo(a)pyrene (BP) exposure on multi-organ carcinogenesis and to evaluate the effects of a well-recognized antioxidant, N-acetyl-L-cysteine (NAC), on neoplasia. We selected the p53 heterozygous Tg.AC (v-Ha-ras) mouse model for our studies because these mice possess a carcinogen-inducible ras oncogene and one functional p53 tumor suppressor allele. Both mutations occur frequently in human cancers. In a 2 x 2 experimental design, both female and male mice were fed basal diet alone or containing 3% NAC and administered by gavage corn oil vehicle alone or containing 20 mg BP/kg body weight given twice weekly for 10 weeks. Mice (n = 15 for each grouping and sex) were subsequently observed an additional 18 weeks followed by tissue collection for evaluation of multi-organ pathology. Benzo(a)pyrene increased neoplasia in the thymus, spleen, stomach, and hematopoietic system after 28 weeks. We observed modest NAC-associated decreases in BP-induced pathology of the liver, papilloma formation and hyperplasia in the forestomach, and the occurrence of malignant lymphoma. Benzo(a)pyrene exposure reduced survival to approximately 40% in male mice, suggesting toxicity; however, survival in control groups was approximately 60%. Survival decreased to approximately 30% for females in all groups. We noted a clear, but nonsignificant, 15% decline in body weights of male, but not female, mice fed NAC, although food intake did not differ. Collectively, the data suggested carcinogen and antioxidant-associated effects on neoplasia that appeared sex-dependent. Thus, this novel short-term bitransgenic model may potentially be useful for testing dietary modulation of carcinogenesis.

Solitary borrelial lymphocytoma in adult patients.

During the period from 1986 to 2000, 85 adult patients with solitary borrelial lymphocytoma were diagnosed at the Department of Infectious Diseases, University Medical Centre Ljubljana, Slovenia. There were 36 (42.4%) females and 49 (57.6%) males with a median age of 49 (15-74) years. Borrelial lymphocytoma was located on the breast (nipple--areola mammae region) in 68 (80%) patients, on the ear lobe in eight (9.4%), and in other locations in nine (10.6%). A concomitant erythema migrans enabling clinical diagnosis of Lyme borreliosis was registered or reported in 67 (78.8%) patients. Fifteen (17.6%) patients had no accompanying symptoms, 34 (40%) reported local and constitutional symptoms, 23 (27.1%) recounted only local symptoms, and 13 (15.3%) patients had solely constitutional symptoms. Clinical findings indicating early disseminated borrelial infection were observed at the first visit in 12 (14.1%) patients: six (7.1%) had multiple erythema migrans, one had meningitis, one meningoradiculitis and arthritis, one radiculoneuritis and arthritis, one peripheral facial palsy and concomitant meningitis, and two arthritis. In addition, one of the patients with borrelial lymphocytoma on the breast had acrodermatitis chronica atrophicans. A seropositive response to borrelial antigens was found in 30 (35.3%) patients at the initial examination. In 11/46 (23.9%) patients, infection with Borrelia burgdorferi sensu lato was confirmed by isolation of the agent from lymphocytoma tissue. Eight out of nine (88.9%) typed borrelial strains were found to be B. afzelii, and one (11.1%) B. bissettii. Patients were treated with doxycycline, azithromycin, amoxycillin, cefuroxime-axetil, phenoxymethylpenicillin, or ceftriaxone. Median time to complete disappearance of lymphocytoma was 28 days (range 7-270 days) after the institution of antibiotic treatment; disappearance took longer in patients with prolonged duration of the skin lesion prior to treatment. Treatment failure was registered in 11 (12.9%) patients who were later re-treated. The outcome of borrelial infection assessed at the end of a follow-up period of one year was favourable.

The histopathology of routine tonsillectomy specimens: results of a study and review of literature.

Controversy continues to attend the routine histologic examination of tonsillectomy specimens. We performed a retrospective evaluation of 400 tonsil specimens removed from 200 patients. We found that 68.3% of the specimens contained reactive lymphoid hyperplasia, 13.5% had follicular hyperplasia, 10.0% represented acute or chronic tonsillitis, and 7.5% were normal. Only one case of malignancy was detected: a non-Hodgkin's lymphoma in one tonsil of a patient who was a cigarette smoker and who had asymmetric tonsils. The results of our study, taken in combination with data already published in the literature, indicate that routine histologic examination of tonsillectomy specimens is unnecessary and results only in added costs and a loss of man-hours. However, in patients who have certain preoperative risk factors, a histopathologic evaluation of tonsillar specimens remains mandatory.

Ocular adnexal reactive lymphoid hyperplasia in children.

AIM: To describe the clinical and histopathological features of ocular reactive lymphoid hyperplasia in children, and review the literature regarding this entity. MATERIALS AND METHODS: In this retrospective, interventional case series, a chart review was performed of three patients diagnosed with reactive lymphoid hyperplasia. Details of clinical presentation, ocular and systemic examination findings, management and subsequent course were noted. RESULTS: Three children, aged 9-14 years presented with ocular adnexal masses (two unilateral and one bilateral) with 7-12 months duration. Ocular examination revealed discrete nasal conjunctival masses in two patients, and bilateral eyelid fullness and conjunctival chemosis in the third patient. Systemic evaluation and laboratory tests were normal in all patients. Orbital imaging showed lacrimal gland enlargement in one patient. Histopathological evaluation with immunohistochemical markers established the diagnosis of reactive lymphoid hyperplasia. Two patients underwent surgical excision with complete resolution. All patients have remained stable and at their last follow-up have showed no evidence of recurrence, transformation, or systemic involvement. CONCLUSION: Reactive lymphoid hyperplasia, though uncommon in children, can have a favorable outcome with timely intervention.

Contact hypersensitivity in patients with primary cutaneous lymphoproliferative disorders.

BACKGROUND: One of the suggested causes of primary cutaneous lymphoproliferative disorders is persistent antigenic stimulation. OBJECTIVE: To study the prevalence of contact hypersensitivity in patients with primary cutaneous lymphoproliferative disorders other than mycosis fungoides (MF). MATERIALS AND METHODS: Thirty consecutive patients with primary cutaneous lymphoproliferative disorders other than MF were patch tested to a European Standard & partial metal series. The results were compared with those of 792 consecutive patients with other skin diseases referred to our clinic and a large published series of 9760 healthy individuals from North America. RESULTS: Twenty-two patients with primary cutaneous lymphoma other than MF and eight patients with pseudolymphomas were included in the study. Altogether there were 23 positive patch tests in 13 patients. Only the prevalence of positive patch tests to cobalt (5/30 patients = 17%) was found to be significantly higher in the studied group than in the two control groups (P<0.01 and P=0.05, respectively). The contact hypersensitivity to cobalt and the other allergens, however, could not be related causally to the pathogenesis of the lesions. CONCLUSIONS: The relative prevalence of contact hypersensitivity to cobalt only was found to be increased in a group of primary cutaneous lymphoproliferative disorders, but a causal relationship to the lymphoproliferative disorders could not be established.