Soft tissue Rosai-Dorfman disease: 29 new lesions in 18 patients, with detection of polyomavirus antigen in 3 abdominal cases.

Soft tissue Rosai-Dorfman disease (STRDD) is rare, previously reported only as single cases and few series. Simian virus 40 (SV40), a polyomavirus, has been identified in lymphoid processes and has a controversial role in neoplasia etiology. Occasional cytoplasmic pink granular inclusions and nuclear changes led us to explore a viral etiology. Only unpublished STRDD from our files with adequate material, soft tissue location, and diagnostic confirmation were included. Immunohistochemistry and follow-up were obtained. Eighteen STRDD patients, 4 male and 14 female, had 29 lesions; 5 with 2 or more lesions. Ages ranged from 8 to 81 years (mean 42.6 years and median 42.5 years). Soft tissue Rosai-Dorfman disease locations include trunk or proximal extremity (n = 19), distal extremity (n = 5), "abdominal" (n = 3), face (n = 1), and unknown subcutaneous site (n = 1). Sizes ranged from 0.5 to 13.7 cm (median, 2.4 cm). Previous disease included lymphoma, buttocks injection site, diabetes and hypothyroidism, and radiation for chronic dermopathy. No patients had a preceding or concurrent known viral infection; none had lymphadenopathy at present. None were known to be immunocompromised. Soft tissue Rosai-Dorfman disease was rapidly progressing. Initial pathologic diagnosis ranged from Rosai-Dorfman disease or inflammatory pseudotumor to inflammatory malignant fibrous histiocytoma. Grossly STRDDs were multilobulated, tan-yellow, and firm; morphologically, circumscribed, and subcutaneous-based. All had sheets of polygonal histiocytes with abundant pale eosinophilic cytoplasm, emperipolesis, plasma cells, and lymphocytes scattered and within clusters. Focal spindle cell change and mild pleomorphism were each observed in 3 patients; 2 had focal necrosis, none with mitoses. Small granular pink cytoplasmic inclusions and nuclear viral-like changes were observed. By immunohistochemistry, all STRDDs were positive for S100 protein, negative for CD1a, Epstein-Barr virus, and latent membrane protein, yet 3 (all abdominal, 1 multicentric) of the 9 studied were focally positive for cytoplasmic and nuclear SV40 polyomavirus. All were treated by local excision. Follow-up on 14 patients older than 8 to 16 years revealed recurrence in 3 patients with persistent multiple lesions, one with abdominal location. There were no metastases or death from disease. Soft tissue Rosai-Dorfman disease is a rapidly evolving, mostly solitary and nonrecurrent trunk and proximal extremity subcutaneous lesion in middle-aged females. More than one third can have persistent multicentric disease. It is important to recognize STRDD, to separate it from malignancy. Epstein-Barr virus/latent membrane protein was negative but polyomavirus was positive in 3 patients with abdominal STRDD, one with multicentric persistent disease. The relationship of polyomavirus to the evolution of abdominal STRDD should be further explored.

A preliminary examination of the role of NFAT 3 in human skin, cultured keratocytes and dermal fibroblasts.

BACKGROUND: Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis.The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). METHODS: RT-PCR and Western Analysis were used to investigate the presence of NFAT-3 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-3 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-3 localisation in these biopsies using a well characterized anti-NFAT-3 antibody. RESULTS: The NFAT-3 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. The expression of NFAT-3 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. As with NFAT 1, NFAT 2 and recently NFAT 5, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-3 in cultured keratocytes but with different kinetics. CONCLUSION: These data provide the first evidence of that NFAT-3 is expressed in normal skin, psoriasis and that NFAT-3 functionally active in human keratocytes and that nuclear translocation of NFAT-3 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-3 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis.

Modulation of NFAT-5, an outlying member of the NFAT family, in human keratinocytes and skin.

BACKGROUND: Cyclosporin A (CsA) and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). NFAT compose a family of transcription factors that are turned on during T cell activation. AIMS: To study the expression of NFAT-5 mRNA and protein in normal human keratinocytes and to investigate the cellular and subcellular pattern of expression of NFAT-5 in normal human skin and psoriasis, and analyze effects of different agonists and ultraviolet radiation on NFAT-5 in normal human skin. METHODS: Tissue cultures, Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), Western analysis, immunostaining, confocal microscopy. RESULTS: Sequencing of RT-PCR products confirmed the identity of the product that showed 100 % homology with the predicted NFAT-5 sequence. anti-NFAT-5 mainly detected a single band in cultured keratinocytes and dermal fibroblasts using Western analysis. Immunohistochemistry showed that epidermal keratinocytes and dermal fibroblasts in normal human and psoriatic skin express NFAT-5. NFAT-5 showed predominantly nuclear localization in epidermal keratinocytes and dermal fibroblasts within five normal adult skin biopsies. Our data also suggest that UV irradiation reduces NFAT-5 nuclear localization within the epidermis. Unlike NFAT 1-4, NFAT-5/TonEBP was localized to both nucleus and cytoplasm of cultured keratinocytes. Cyclosporin A induces nuclear membrane translocation of NFAT-5 in cultured keratinocytes and raffinose (a hypertonicity inducing agent) induces more nuclear localization of NFAT-5 compared to untreated cells. In addition, differentiation-promoting agonists that induce sustained rise in intracellular calcium did not result in changes in NFAT-5 localization in cultured keratinocytes. CONCLUSION: These studies provide the first observation of expression of NFAT-5/TonEBP mRNA protein in cultured keratinocytes and dermal fibroblasts and possible functional regulation in cultured keratinocytes. CsA and raffinose effects on NFAT-5/TonEBP in cultured keratinocytes suggest diverse intracellular signaling pathways for NFAT-5/TonEBP in these cells, and that NFAT-5/TonEBP might function to translate different extracellular stimuli into appropriate functional responses.

Expression, localisation and functional activation of NFAT-2 in normal human skin, psoriasis, and cultured keratocytes.

Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis. The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT). As calcineurin and NFAT 1 have been shown to be functionally active in cultured human keratocytes, expression of other NFAT family members such as NFAT-2 and possible functional activation was investigated in human keratocytes. RT-PCR and Western Analysis were used to investigate the presence of NFAT-2 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-2 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-2 localisation in these biopsies using a well characterized anti-NFAT-2 antibody. The NFAT-2 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. Moreover, the expression of NFAT-2 in normal skin, non-lesional and lesional psoriasis showed a striking basal staining suggesting a role for NFAT-2 in keratocytes proliferation. A range of cell types in the skin express NFAT-2. The expression of NFAT-2 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. In these experiments the author assessed the expression, localization of NFAT-2 in cultured human keratocytes and measured the degree of nuclear localisaion of NFAT-2 using immunofluorescence and confocal microscopy and whether CsA and tacrolimus inhibit NFAT-2 nuclear translocation. As with NFAT 1, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-2 in cultured keratocytes but with different kinetics. These data provide the first evidence of that NFAT-2 is expressed in normal skin, psoriasis and that NFAT-2 functionally active in human keratocytes and that nuclear translocation of NFAT-2 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-2 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis. Thus, supporting our previous work data that calcineurin/NFAT is functionally active not only in T cells, but in skin cells.

Synovial sarcoma involving the head: analysis of 36 cases with predilection to the parotid and temporal regions.

Synovial sarcoma involving the head is rare, and data on the clinicopathologic characteristics of such tumors are scant. In this study, we examined 36 synovial sarcomas of the head excluding tumors in the oral cavity, sinonasal tract, submandibular area, neck, and intracranial space. There were 19 men and 17 women with a mean age of 35 years (range: 4 to 85 y). There was a marked predilection for the parotid (n=14) and temporal regions (n=9), and cheek (n=4). Other locations included mastoid area (n=2), infratemporal fossa (n=2), and one each from the supra-auricular scalp, maxillary, submaxillary, mandibular, and nasolabial regions. Histologically, 25 examples were of monophasic type, 10 were biphasic. Five of these cases contained a poorly differentiated Ewing sarcoma-like component and 1 was purely poorly differentiated. Histologically, 9 tumors involved skeletal muscle, 4 parotid gland (focally or in the interlobular septa), and 1 intertrabecular spaces of bone; the others involved subcutis or fascia and rarely skin. The tumor size ranged from 0.6 to 7.0 cm (median: 3.5 cm) and mitotic activity varied from <1 to 85 per 10 high-power fields (HPFs) (median, 6/10 HPFs). Keratin-positive tumor cells were detected in 19 of 19 monophasic and 1 of 1 of poorly differentiated tumors that were examined. SS18 gene rearrangement was confirmed in all 14 cases examined (3 biphasic and 11 monophasic tumors). Follow-up on 29 patients revealed that 11 were alive without disease from 2 to 31 years (median, 14 y). Ten patients died of disease 1 to 18 years after the diagnosis (median, 3 y); most of these patients had a tumor >5 cm and 6 of 10 had mitotic counts >10/10 HPFs. One patient died of an unrelated cause (metastatic melanoma) and 7 died of unknown causes. Four other patients had subsequent malignancies, including carcinomas of the breast, esophagus, rectum, and parotid gland. The latter was possibly radiation-induced, diagnosed 30 years after the synovial sarcoma. Synovial sarcoma of the head has a striking predilection for the parotid and temporal regions and the prognosis varies with many patients having long tumor-free survivals.

Epithelial sheath neuroma: be aware of benign perineural invasion!

Perineural involvement by epithelial cells is usually considered as a sign of malignancy and is seen in a variety of malignant skin neoplasms. However, there are other benign conditions characterized by the presence of perineural involvement by epithelial cells. We present a case of epithelial sheath neuroma in a 43-year-old male. The clinicopathological features of this newly described entity are discussed together with the differential diagnosis and the different hypotheses of pathogenesis. Both pathologists and dermatologists should be aware of this entity to avoid misdiagnosis of malignancy.

Disseminated coccidioidomycosis: a case report from the United kingdom.

We reported the first case of disseminated coccidioidomycosis from the UK successfully treated with amphotericin B, where skin biopsy was the initial clue for the correct diagnosis.

Primary gallbladder sarcoma: a clinicopathologic study of 15 cases, heterogeneous sarcomas with poor outcome, except pediatric botryoid rhabdomyosarcoma.

BACKGROUND: Primary gallbladder sarcoma (PGBS) is rare, with only 39 documented cases, with the predominant type being leiomyosarcoma. DESIGN: Cases recorded as "gallbladder sarcoma" were retrieved from our files; the clinicopathologic features were reviewed and recorded. Only primary gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed tumors (carcinosarcoma or sarcomatoid carcinoma), tumors extending into the gallbladder from the abdomen, or sarcoma with other known primaries were excluded. RESULT: PGBS occurred in 4 males and 11 females with the adult median age of 68.5 (range: 24 to 88 y, n=12) and 3 children ages 1.5 to 3 years, the latter all with botryoid embryonal rhabdomyosarcoma. Patients presented with acute and/or chronic cholecystitis, abdominal pain, weight loss, pruritus, elevated alkaline phosphatase and bilirubin, and leukocytosis. The median tumor size was 4.5 cm, mean tumor size 5.7 cm, and range 2.0 to 14.0 cm. Most PGBS involved the entire wall and ulcerated the mucosa. PGBSs were diagnosed as 7 myxofibrosarcomas [malignant fibrous histiocytoma, storiform pleomorphic to myxoid, 2 with an unusual fibromyxoid sarcoma-like (Evans-like), and pleomorphic hyalinizing angiectatic tumor-like mixture], 2 leiomyosarcomas, 1 gastrointestinal stromal tumor-like (GIST-like), 3 botryoid embryonal rhabdomyosarcomas (RMS), and 2 epithelioid angiosarcomas. Diagnosis was based on morphology and immunohistochemistry. A diagnosis of LMS required myoid-intersecting fascicles and diffuse, strong immunoreactivity for smooth muscle actin +/- desmin. RMS revealed myxoid grape-like hypocellular tumor with stellate cells, mild atypia, mitoses and desmin, and myoregulatory protein (MyoD1) and skeletal muscle-specific myogenin (Myf4) reactivity. The GIST-like sarcoma was palisaded and myoid-like but failed to stain for CD34 or CD117. Angiosarcomas demonstrated an extravascular proliferation of atypical epithelioid endothelial cells, and mitotic activity. All cases were negative for S100 protein, HMB45, keratins, and CK18. All patients received cholecystectomy and 6 known adjuvant therapy. Follow-up of 12 revealed that 7 patients died of disease within 3 weeks to 1 year and 4 months after diagnosis, 3 died of unknown causes, and 2, both adjuvant therapy treated botryoid RMS in young children, were alive without disease 11 and 27 years later. CONCLUSIONS: PGBSs are rare. Carcinosarcoma, spindle cell carcinoma (by use of keratins and CK18), and melanoma must first be excluded. A variety of sarcoma types are found, yet malignant fibrous histiocytoma is the predominant variant, more common than LMS. GIST is a controversial sarcoma in gallbladder; angiosarcoma can rarely occur in this location. PGBS mainly occur in older female adults and have overall poor prognosis. A subgroup of adjuvant therapy-treated botryoid embryonal RMS in the gallbladder of young children, although rare, can have excellent prognosis.

Dendritic cell sarcomas/tumours of the breast: report of two cases.

Extranodal follicular dendritic cell sarcoma/tumours (FDCS/Ts) and interdigitating dendritic cell sarcoma/tumours (IDCS/Ts) are rare neoplasms. We present two cases of FDCS/T and IDCS/T of the breast. The FDCS/T case (case 1) presented in a 31-year-old woman and the IDCS/T case (case 2) in a 67-year-old woman who both showed a firm lump in the left breast. The FDCS/T lesion superficially appeared as an anaplastic carcinoma and the IDCS/T was reminiscent of a spindle cell sarcomatoid carcinoma. Nevertheless both lesions were negative for keratins while case 1 displayed neoplastic cells strongly positive for CD21, vimentin and focally for CD68 and S-100 protein. The tumour cells of case 2 were positive for S-100, CD68 and CD45. In breast, an unusual keratin negative tumour composed predominantly of spindle cells arranged in fascicles, storiform pattern or whorls with a lymphoid rich stroma should raise suspicion for FDCS/Ts or IDCS/Ts. The distinction from malignant tumours with similar features is discussed.

Infection and cervical neoplasia: facts and fiction.

Whilst there is strong evidence that human papillomavirus (HPV) is the principal aetiological agent in cervical neoplasia, some other sexually transmitted agents may either contribute or protect against cervical carcinogenesis, such as the herpes virus family (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human immunodeficiency virus (HIV) or Chlamydia trachomatis (CT). Epidemiological studies suggest that HSV may have a role in cervical neoplasia, but there is no clear supportive experimental evidence. Serological studies have also failed to reveal a difference in the prevalence of antibodies to CMV and EBV between patients with cervical cancer and controls. However, longitudinal seroepidemiological studies have provided evidence that CT is an independent risk factor for the development of cervical squamous carcinoma and this association is serotype specific. The increased risk of cervical neoplasia in patients infected with HIV has been recognised for over a decade and HIV may interact with HPV either by alternating HPV gene transcription or by immunosuppression. Finally extensive experimental and limited epidemiological evidence suggests that adeno-associated viruses (AAV) may have antioncogenic activity in man and may protect against the development of cervical cancer. At present the mechanism of this action is unclear but may relate to AAV-induced regulation of HPV gene expression and the HPV life cycle. In this review we summarize the current literature relating to the associations and mechanisms of cervical carcinogenesis by each of these infectious microorganisms.

Gallbladder sarcoma: a clinicopathological study of seven cases from the UK and Austria with emphasis on morphological subtypes.

BACKGROUND: Primary sarcoma of the gallbladder (PGBS) is rare, with only 40 cases reported in the literature. Most of these have been diagnosed as leiomyosarcoma. We aimed to evaluate the histological features of a case series of this rare tumor and correlate these with clinical features. DESIGN: Cases recorded as "gallbladder sarcoma" from different institutes were reviewed and the clinicopathological features of these cases were recorded. Only primary gallbladder wall mesenchymal tumors were included. Epithelial tumors, mixed tumors (carcinosarcoma or sarcomatoid carcinoma), and tumors extending into the gallbladder from the abdomen or sarcoma with other known primaries were specifically excluded. RESULT: PGBS occurred in one male and six females with a median age of 70 (range 64-82) years. Patients presented with acute or chronic cholecystitis, abdominal pain, weight loss, and pruritus. They were generally found to have elevated alkaline phosphatase and bilirubin, and leukocytosis. Tumors ranged from 1.1 to 4 cm with a median size of 3 cm. Most PGBS arose in the body but one arose in the fundus. All tumors were associated with ulcerated mucosa. Based on morphological and immunohistochemical features of the PGBS, there were three myxofibrosarcomas (malignant fibrous histiocytoma, MFH, storiform pleomorphic), one leiomyosarcoma (LMS), one angiosarcoma (AS), and two liposarcomas (LS). All patients received cholecystectomy and three received adjuvant chemotherapy. Follow-up revealed that six patients died of the disease 6 weeks to 2 years after diagnosis and one died of unrelated causes. CONCLUSION: PGBS are rare and mainly occur in the gallbladder body in middle-aged females. They generally present with acute cholecystitis and have a very poor prognosis. A variety of sarcoma types are found with MFH being the predominant variant.

Cost-effectiveness of active versus conservative colposcopic management of mild dyskaryosis.

Management of mild dyskaryosis remains controversial. In this study, we compared the cost-effectiveness of active versus conservative colposcopic management of women presenting with mild dyskaryosis in two different hospital settings. All women presenting in 2001 with a mild dyskaryotic smear and requiring colposcopy were studied in two different clinical settings (70 women at Darent Valley Hospital (DVH) and 327 at St George's Hospital (SGH)). At DVH, treatment is offered should there be any evidence of cervical intraepithelial neoplasia (CIN). On the other hand, a more conservative approach of cytological and colposcopical follow-up is offered to patients with evidence of low-grade disease at SGH. The outcome of both groups of patients was determined in terms of the number of colposcopy visits per patient, the risk of missing disease as a consequence of patients lost to follow-up and hospital costs as well as costs to patient over a four-year period. The majority (70%) of DVH patients had 1-2 colposcopy visits whereas the majority (60%) of SGH patients had 3-7 visits. At SGH 44% of untreated patients were lost to follow-up and an unknown number of those might have had high-grade disease. Active management is more cost-effective compared with conservative management ( pound323 and pound589 as cost per patient effectively treated in the two hospitals respectively). In conclusion, active management of low-grade disease is associated with lower hospital and patient costs compared with the conservative strategy.

A practical and comprehensive immunohistochemical approach to the diagnosis of superficial soft tissue tumors.

Soft tissue tumors include neoplasms of specific and unknown lineages, and, therefore, lineage markers of smooth muscle, skeletal muscle, endothelial, epithelial and Schwann cells have proven useful in everyday practice. However, groups of tumors remain that are defined essentially on grounds of histology; others can be defined by molecular genetic studies. The complex distribution patterns of many antigens and loss of some differentiation antigens in malignant tumors often necessitate the use of panels of antibodies. Optimally such panels should address all significant differential diagnostic alternatives. There is little doubt that numerous new differentiation markers will appear in the future. The evaluation of tumor proliferation, apoptosis, and cell cycle control will give new information related to tumor biology and prognosis.

Cutaneous lobomycosis: a delayed diagnosis.

The occurrence of lobomycosis outside central and South America is extremely rare. Herein we report 2 extraordinary cases of lobomycosis in 2 South African patients seeking medical attention at the Liverpool School of Hygiene and Tropical Medicine. The first patient presented with a 32-year history of a lesion on his left foot, with a further lesion subsequently developing on the right foot within the year. Six years ago he developed nontender keloid-like lesions on his left arm and on the face. The second patient is a 16-year-old black South African man who presented with a 2-year history of an ulcerating fungating tumor on his back. Microscopically, biopsies from both patients consisted of a diffuse granulomatous dermal inflammatory cell infiltrate composed of numerous multinucleate giant cells, and histiocytes, which contained rounded organisms with refractile walls, imparting a characteristic sievelike morphology; there were admixed acute and chronic inflammatory cells. Grocott's methenamine silver stain, and periodic acid Schiff (positive), demonstrated many uniform spherical to oval yeastlike organisms arranged singly or in small chains connected by thin tubular connections. In conclusion, we report 2 unique and exceedingly rare cases of cutaneous lobomycosis.

Primary cutaneous amebiasis with a fatal outcome.

We report a fatal case of disseminated amebiasis in a young African woman, which initially presented with an ulcerated cutaneous lesion on the left flank. The causative organism was confirmed by examination of a wet drop preparation from the ulcer discharge and by skin biopsy. The patient was not immunosuppressed and was treated unsuccessfully with metronidazole. Postmortem examination revealed the presence of intestinal amebiasis complicated by a liver abscess.

Superficial acral fibromyxoma: a clinicopathological analysis of 32 tumors including 4 in the heel.

AIMS: To examine a series of superficial acral fibromyxomas (SAFs) and discuss our experience with this new entity and its differential diagnosis in the past 5 years. METHODS AND RESULTS: Thirty-two new cases of SAF were studied between 2001 and 2006. The patients included 22 males and 10 females with an age range between 23 and 82 years (mean 51, median 53) presenting with a solitary mass or nodule with an average size of 2 cm. The sites were the toes (n = 15) and fingers (n = 13) with 66.6% of tumors close to or involving the nail bed. Four tumors occurred in the heel where SAF has not been previously observed. Local recurrences developed in 3 of 14 patients (22%). Histologically, all tumors presented with spindle cells with a vague storiform and fascicular pattern embedded in a myxoid/fibromyxoid/collagenous stroma. A characteristic immunophenotype included CD34+, CD99+/- and EMA+ focally. One case showed moderate cytological atypia with 1 mitosis per 10 HPF, but a 4-year follow up showed no evidence of recurrence. CONCLUSION: Thirty-two new cases of SAF confirm this tumor as a reproducible entity. Occurrence in the heel, a new site for this tumor, was reported in four cases. Recurrence rate of this tumor may exceed 20%.

"Macular arteritis": a latent form of cutaneous polyarteritis nodosa?

Recently described macular arteritis presents as asymptomatic hyperpigmented macules, runs a chronic, indolent course, and shows lymphocytic arteritis at various stages of evolution ranging from fibrinoid necrosis to endarteritis obliterans. Herein, we present another case that was clinically suspected to be unilateral plantar pompholyx. A 47-year-old male presented with a 2-month history of persistent, reticulated, asymptomatic, nonblanching erythematous and brawny macules, and scattered, slightly scaly papules over the plantar instep of his left foot. Two punch biopsies extending to the subcutis revealed healed arteritis (endarteritis obliterans with fragmented elastic lamina) in the subcutis in one biopsy and purpura and hemosiderin deposition surrounding small subcutaneous arterioles and venules in the second. Additional histologic features included lymphocytic eccrine hidradenitis and chronic spongiotic dermatitis. Extensive laboratory work did not reveal evidence of systemic disease. Despite topical corticosteroid therapy, he has had persistent, asymptomatic disease after 6 months follow-up. The differential diagnoses considered included pigmented purpuric dermatitis, perniosis (chilblains), plantar eccrine hidradenitis, Buerger disease, livedo vasculopathy, and cutaneous polyarteritis nodosa. Cutaneous polyarteritis nodosa also runs a benign course and is denoted by muscular vessel vasculitis, which can resolve with retiform hyperpigmentation. Based on these overlapping clinical-pathologic features, macular arteritis might represent a latent, non-nodule forming chronic variant of cutaneous polyarteritis nodosa.

Granular perineurioma: the first report of a rare distinctive subtype of perineurioma.

Perineurioma represents a relatively recently described neoplasm in the spectrum of benign peripheral nerve sheath tumors composed of perineurial cells staining immunohistochemically positive for epithelial membrane antigen. Although intraneural, extraneural and sclerosing perineurioma, rare variants of perineurioma, do occur, and knowledge of them is important in the differential diagnosis of mesenchymal tumors of different lines of differentiation and more importantly if their clinical course differs from that of other perineuriomas. We report herein the first case in the world literature of granular perineurioma arising in the dermal and subcutaneous tissues of the trunk of a 28-year-old female. The diagnosis was confirmed morphologically and immunohistochemically. More interestingly, 3 years later the patient complained of right lower extremity pain, for which magnetic resonance imaging studies showed an intraneural perineurioma confined to the sciatic nerve. The latter finding was confirmed both histopathologically and immunohistochemically to have exactly the same appearances of the original dermal and subcutaneous mass. Neoplastic cells stained positively for epithelial membrane antigen and for the newly described antibodies claudin-1 and glut-1. Interestingly, the granular component of this large tumor (4.5 cm in maximum diameter) was negative for S100, but positive for NKI-C3. The morphology, immunohistochemistry, and the clinical behavior for this tumor and the differential diagnoses are discussed.

Gastric changes following colchicine therapy in patients with FMF.

BACKGROUND: Familial Mediterranean fever (FMF) is also called recurrent polyserositis. The salient features of this disease include brief recurrent episodes of peritonitis, pleuritis, and arthritis, which are usually associated with fever. Colchicine is highly effective in the treatment of FMF and in preventing the development of recurrent attacks and amyloidosis, and it is essential to make the correct diagnosis and institute daily therapy with colchicine (0.5-0.6 mg bid). Colchicine is used to treat a variety of conditions but it is known to have gastrointestinal (GI) side effects. In this study, effects of colchicines on the gastrointestinal tract were evaluated in patients with FMF treated with colchicine. METHODS: Biopsies were reviewed from 43 patients attending Ain Shams University Hospital (Egypt) who were diagnosed with FMF and treated with colchicine. One-hundred and twelve GI biopsies, obtained over a 14-year period, were reviewed. This included biopsies from stomach body (38), stomach antrum (50), and colon (24). In addition, gastric biopsies were reviewed from 17 control patients who did not have FMF and were not on colchicine. RESULTS: Three patients known to have FMF and on colchicine therapy showed typical histological features of colchicine (metaphase mitoses, epithelial pseudoproliferation, mucin depletion, and frequent apoptosis). These features were seen only in gastric antral biopsies and not in colonic biopsies. None of the control group showed the characteristic morphological features of colchicine toxicity. CONCLUSION: This is the first report of histological changes seen in the stomach following colchicine therapy. In contrast with previous reports, we did not find any definitive change in the large intestine. Our data show that gastric changes can be encountered in symptomatic patients who have recently had colchicine. If these finding are seen histologically, they merit correlation with the clinical impression and should not be interpreted as toxicity in isolation.