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A 70-year-old patient with a chronic cutaneous ulcer treated by minocycline hydrochloride developed hyperpigmentation of the forearms. Biopsy material was studied by light microscopy, electron microscopy and X-ray energy spectroscopy. Granular gold-brown pigment was found in dermal histiocytes and eccrine myoepithelial cells, which gave positive reaction with Prussian blue and Fontana-Masson stains. Electron microscopy revealed intracytoplasmic granules of dark, homogeneous material and small line particles. X-ray energy spectroscopy showed iron and other elements in smaller amounts. The different types of minocycline-related hyperpigmentation and the possible patho-mechanism are discussed with special regard to the importance of the diagnostic methods. [ABSTRACT FROM AUTHOR]

Twelve cases were reviewed of squamous cell carcinoma of the nail bed, with emphasis on the aetiological role of human papillornavirus (HPV) infection and radiation damage. Using a hybridization technique, similar HPV genomes were detected in a uterine cervical neoplasia and a subungual squamous cell carcinoma in the same patient. [ABSTRACT FROM AUTHOR]

Setting: A county jail., Objective: To characterize the treatment of latent tuberculosis infection and the impact on treatment completion of the 2-month rifampin and pyrazinamide regimen as compared to the traditional 6- to 12-month isoniazid regimen among persons incarcerated at a county correctional facility., Design: Retrospective review of tuberculosis records from January 1998 to December 2000., Results: Of 2127 inmates who were tuberculin skin test positive, 146 were started on treatment. This was generally limited to those expected to remain incarcerated long enough to complete the course of treatment. Completion rates were 88% (67/76) for the 2-month and 74% (51/69) for the 6- to 12-month courses (P = 0.03), and 82% overall. The two regimens were similarly tolerated, but inmates on isoniazid were more likely to be released (despite longer projected incarceration) and not complete treatment once in the community. Thirty-seven per cent of persons for whom treatment was not indicated by the previous guidelines should have had treatment by the new guidelines., Conclusion: The 2-month rifampin/pyrazinamide regimen had a higher completion rate than the longer isoniazid regimen, without additional toxicity, and allowed more patients to be treated. Latent tuberculosis treatment targeted to those able to complete the regimen in jail yields high completion rates.

Immunoperoxidase-staining methods were used to examine the expression of hMLH1, hMSH2, and hMSH6 mismatch repair (MMR) proteins in 50 melanocytic lesions. Microsatellite instability (MSI), screened previously in these lesions by polymerase chain reaction-based microsatellite assay, showed low-level microsatellite instability (MSI-L) in 11 of 22 melanocytic dysplastic nevi (MDN) and two of nine primary cutaneous malignant melanomas (CMMs) but not in the benign melanocytic nevi (BN). Mismatch repair proteins were widely expressed in the epidermis and adnexal structures. All lesions showed positive immunoreactivity with a gradual decrease in the MMR staining values during the progression from BN to MDN to CMMs. The average percentage of positively (PP) stained cells for hMLH1, hMSH2, and hMSH6 in BN was 85.50 +/- 1.95, 77.90 +/- 4.50, and 87.11 +/- 1.85, respectively. The PP cell values in CMMs were significantly reduced as compared with BN (75.22 +/- 3.57, p= 0.01; 56.11 +/- 8.73, p= 0.02; 65.22 +/- 6.47, p = 0.0002 for hMLH1, hMSH2, and hMSH6, respectively). No comparable significant difference was found between microsatellite stable and MSI-L lesions (p = 0.173, p = 0.458, and p = 0.385), suggesting a lack of correlation between MMR expression and MMR function. There was a direct correlation between PP cell values of hMSH2 and hMSH6 (R = 0.39, p = 0.008), implying that their expression could be regulated by a common mechanism. Thus, an important finding of these studies was the reduction of MMR protein levels in CMMs; whether this reflects underlying genetic or epigenetic mechanisms is still to be determined.

Introduction: the length of DNA repetitive sequences (microsatellite instability (MSI)) represent distinct tumorigenic pathways associated with several familial and sporadic tumors., Material and Methods: To investigate the prevalence and frequency of MSI in melanocytic lesions, the polymerase chain reaction (PCR)-based microsatellite assay was used to examine formalin-fixed, paraffin-embedded tissues of 30 benign melanocytic nevi, 60 melanocytic dysplastic nevi (MDN), and 22 primary vertical growth phase cutaneous malignant melanomas (CMM). Twenty-four microsatellite markers at the 1p, 2p, 3p, 4q and 9p chromosomal regions were used., Results: MSI was found at 1p and 9p in MDN and CMM but not in benign melanocytic nevi. The overall prevalence of MSI was 17/60 (28%) in MDN and 7/22 (31%) in CMM. The frequency of MSI ranged from 2/24 (9%) to 4/24 (17%) and was most commonly found at D9S162. There was a statistically significant correlation between degree of atypia and frequency of MSI (p<0.001) in MDN. There were two MSI banding patterns: band shifts and additional bands., Conclusions: The data presented revealed the presence of low-frequency MSI (MSI-L) at the 1p and 9p regions in both MDN and CMM. Whether the MSI-L pattern reflects a defect in mismatch repair genes is still to be determined.

Objective: To assess the characteristics of patients with perioperative disseminated intravascular coagulation (DIC) and acute ischemic hepatitis after elective aortic aneurysm repair (AAR)., Design: A retrospective case-control study., Setting: A single tertiary referral center., Participants: Between 1982 and 1993, 1966 patients underwent elective AAR. Of these, 10 patients (eight with abdominal and two with thoracoabdominal aneurysms) developed DIC and acute elevation of serum transaminases consistent with acute ischemic hepatitis during or shortly after surgery. The control group included 30 patients matched by age, sex, year of surgery, and aneurysm type and size., Interventions: None., Measurements and Main Results: None of the patients in either group had preoperative hemostatic abnormalities or other causes for DIC. There was no difference between the two groups in the duration of aortic cross-clamping. In all study patients, severe coagulopathy or systemic hypotension developed after the aortic cross-clamp was released. This resulted in significantly increased surgery time after unclamping (p < 0.001), and increased estimated blood loss (p < 0.001). DIC developed within 24 hours, and mean concentrations of aspartate transaminase (4,021 +/- 3,579 IU/L) and lactate dehydrogenase (4,332 +/- 2,903 IU/L) peaked on the second postoperative day. Nine (90%) of the study patients required repeat operations (seven for bleeding), and all of them died; the median survival time was 6 days (mean, 8.3 +/- 8.2 days). Only one patient in the control group needed a repeat operation. Liver infarction or necrosis was seen in all seven patients who underwent autopsy or biopsy., Conclusions: The combination of DIC and acute ischemic hepatitis ("hepatohemorrhagic syndrome") rarely occurs after elective AAR and is associated with a very high mortality rate. DIC was temporally related to the release of the aortic cross-clamp. The cause-effect relationship of this rare syndrome cannot be explained by operative course before the release of the aortic cross-clamp.

The histologic distinction between dermatofibrosarcoma protuberans (DFSP) and the fibrous type of benign fibrous histiocytoma (dermatofibroma, DF) may be extremely difficult. In this study, we evaluated the extent and pattern of immunoreactivity of both CD34 and factor XIIIa in a large number of DFSPs and DFs in order to determine the utility of these markers in their distinction. Using histologic criteria alone, the authors independently evaluated and agreed upon 30 cases of DF and 24 cases of DFSP, and a representative section was stained with antibodies to both factor XIIIa and CD34. Immunopositivity was evaluated semiquantitatively and assigned a score from 0 to 5. CD34 immunoreactivity was seen in 22 (92%) of 24 DFSPs (mean CD34 score, 4.60 +/- 0.3). Only 12 (40%) of 30 DFs showed CD34 immunopositivity (mean CD34 score, 0.6 +/- 0.1). Factor XIIIa was seen in 29 (97%) of 30 DFs (mean factor-XIIIa score, 4.1 +/- 0.3). In contrast, 18 (75%) of 24 DFSPs stained for factor XIIIa (mean factor-XIIIa score, 1.3 +/- 0.2), but in most of these cases the factor-XIIIa-positive cells were felt to be entrapped nonneoplastic dermal dendrocytes. Thus, an immunoprofile using antibodies to CD34 and factor XIIIa is capable of distinguishing between DFSP and the fibrous type of DF in the vast majority of cases, as long as there is recognition that there may be some CD34-positive cells in DFs, as well as some factor-XIIIa-positive cells in DFSPs.

Antimalarial agents have long been known to cause a variety of pigmentary disturbances. Quinidine, a cincha alkaloid and D-isomer of quinine, is widely used for the treatment of ventricular arrhythmias. A paucity of literature, however, exists concerning quinidine-associated hyperpigmentation. We describe a case of focal ceruloderma we believe to be secondary to quinidine therapy.

Central nervous system (CNS) expression of two chemokine mRNAs, encoding monocyte chemoattractant protein-1 (MCP-1) and IFN-gamma-inducible protein (IP-10), was previously shown to be closely related to the onset of clinical signs of murine experimental autoimmune encephalomyelitis (EAE). Chemokine mRNAs accumulated in a striking, transient burst within astrocytes, near inflammatory leukocyte infiltrates. It remained unclear if chemokines functioned to initiate leukocyte entry into CNS tissues, or to amplify the intrathecal inflammatory reaction. To address this issue, we determined the expression of chemokine mRNAs at the earliest evidence of CNS immune-mediated inflammation. For these experiments, mice were sacrificed in pairs at varying times after immunization. Only one member of each pair was symptomatic for EAE at the time of sacrifice. Symptom presence correlated well with histological inflammation at the time of sacrifice. RNA was prepared from two CNS sites, brain and spinal cord, and expression of chemokine mRNAs was analyzed by a sensitive and quantitative reverse transcriptase/polymerase chain reaction dot-blot hybridization assay. CNS expressions of MCP-1 and IP-10 gene were correlated tightly with histological inflammation; indeed, chemokine expression was never detected in the absence of leukocyte infiltrates. In situ hybridizations showed that astrocytes expressed chemokine transcripts. These findings provide new information about mechanisms controlling chemokine mRNA expression during immune-mediated inflammation in EAE and are consistent with a role for chemokines as amplifiers of CNS inflammatory reactions.

Human cutaneous malignant melanoma progresses through a series of well defined clinical and histopathological stages. It has been assumed that the neoplastic progression of this disease advances from a common acquired nevus or dysplastic nevus through the primary radial growth phase (RGP), primary vertical growth phase (VGP), and finally to distant metastasis. However, it has never been directly shown that VGP is clonally derived from RGP. Furthermore, it has not been possible previously to conduct a detailed genetic analysis on pure tumor cells from archival material because the lesions are a heterogeneous mixture of normal and neoplastic cells, and the entire specimen must be excised and fixed for clinical diagnosis. This report describes a new approach designed to identify DNA copy number changes in tumor cells from a series of progressive primary stages of cutaneous melanoma archival biopsies. Under direct high-power visualization, cells are procured with a sterile needle from highly specific areas of the tissue section. DNA is extracted from microdissected cells (normal, RGP, and VGP), PCR amplified, fluorescently labeled, and examined by comparative genomic hybridization to determine DNA copy number changes. Data obtained from three representative cases suggest a clonal derivation of VGP cells from RGP. This approach could be useful in identifying the sequence of genetic changes in progressive cutaneous melanoma stages.

Desmoplastic malignant melanoma is an unusual variant of cutaneous melanoma. Arising from either an occult or recognized superficial melanotic lesion, it evolves into an aggressive, locally recurrent and frequently metastasizing, deep, hard, fibrous tumefaction. A highly confusing clinical and histologic picture makes accurate diagnosis especially difficult. Appropriate treatment is often delayed until time of recurrence. Prognosis is invariably poor if the tumor is not adequately treated primarily. Close follow-up is essential. Since its original description by Conley et al. in 1971, in which 7 cases were presented, fewer than 150 additional cases have been cited. We provide a detailed report of 11 cases of this distinct histopathologic entity. Clinical course, histopathology, surgical management, and prognosis are discussed. It is our hope that this comprehensive review will instill a high index of suspicion among surgeon and pathologist alike, enabling earlier diagnosis and definitive therapy.

A 65-year-old man presented with a history of a giant blue plaque of the parietal scalp since childhood. Biopsy revealed a cellular blue nevus. The blue nevus was observed for 10 years and thought to be unchanged until a new adjacent lesion was noted. Biopsy of the new lesion revealed metastatic malignant melanoma. A wide excision was performed of the original lesion which revealed malignant melanoma arising in a blue nevus. Areas within the blue nevus were consistent with a pilar neurocristic hamartoma, whereas other areas were consistent with a common blue nevus. Subsequent satellite metastases developed, with early metastases resembling blue nevi except for the absence of a stromal component and the presence of hyperchromatic nuclei. Later metastases were typical of metastatic melanoma. This case illustrates the uncommon evolution of malignant melanoma from a blue nevus. The histological features and relationship between melanoma, blue nevus, and pilar neurocristic hamartoma are reviewed.

We report an epidermoid cyst of the scalp with light microscopic and immunohistochemical evidence of human papillomavirus (HPV) infection. Light microscopic features suggesting HPV infection included papillomatosis and hypergranulosis of the cyst lining with the presence of koilocytes. Much of the keratin within the cyst demonstrated parakeratosis. Immunoperoxidase labeling for HPV antigen was noted within koilocytes. Papillomavirus infection has been reported in plantar epidermoid cysts. To our knowledge, this is the first report of a papillomavirus-infected epidermoid cyst in a site other than plantar skin. Light microscopic features of our cases differed from those of the plantar cysts. Epidermoid cysts may be induced by the papillomavirus or the virus may merely infect pre-existing cysts.

Two cases of fibrous papule of the nose (FPN) with granular cell features are presented and discussed. Both lesions have classic architectural features of FPN; however, the main stromal cells show large cytoplasmic granules of the type seen in granular cells. We are uncertain of the significance of these findings. Our hypotheses include a perifollicular granular cell reaction and a granular degenerative change of local dermal dendrocytes.

Erythromelanosis follicularis faciei et colli is uncommon. Fewer than 20 cases have been reported. Except for one case in a woman and one case of unilateral distribution, all other reported cases have been bilateral in young male patients. We report the first case of unilateral distribution in a white girl.

We describe a patient with both Muir-Torre syndrome and alpha 1-antitrypsin deficiency. A keratoacanthoma developed after immunosuppressive therapy for necrotizing vasculitis. To our knowledge, this is the first reported case of Muir-Torre syndrome associated with alpha 1-antitrypsin deficiency.

A case of a severe, locally aggressive fibroblastic reaction to cosmetic silicone injection involving the orbital cone and anterior cranial base is presented. Included is a brief history and description of silicone injection and its complications. Though many facts remain to be discovered, speculation into the possible pathogenesis, with a review of the literature, shows that while silicone continues to be a useful tool for the plastic surgeon, an awareness of the risks, as well as a search for clues to avoid complications, must continue before further liberal use of this material is encouraged.

Three patients are described with cicatricial pemphigoid and positive immunofluorescence findings in the basement membrane zone of mucous glands of the pharynx, mouth, and nose. These findings appear to be unique to cicatricial pemphigoid.

An 84-year-old man was examined for progressive pain, edema, and infiltrating skin lesions on his lower extremities. A skin biopsy specimen confirmed the suspected diagnosis of angioendotheliomatosis proliferans. The clinical course and histologic changes suggested the malignant form of this disease. Treatment with intravenous doxorubicin hydrochloride caused a complete clinical remission.

Two patients with the clinical and histopathologic findings of eosinophilic cellulitis are presented. In one patient there was a definite relationship between upper respiratory tract infection and flare-ups of eosinophilic cellulitis. This patient's condition was superimposed on a long history of chronic urticaria. In the other patient a relationship to recurrent sinusitis was possible but not definite. There were no other contributory underlying skin diseases in either patient. Eosinophilic cellulitis is not likely a disease entity as such but, instead, represents a severe urticarial hypersensitivity reaction to various stimuli. Collagen alteration by eosinophil granules results in flame figure formation and a granulomatous response, which may explain the prolonged persistence of the lesions.

This report describes the findings in a 58-yr-old woman with multiple gastrointestinal polyps, associated with diarrhea, abdominal discomfort, hypoalbuminemia, alopecia, nail atrophy, and pigmentary changes. The patient met the criteria of the Cronkhite-Canada syndrome. Pathological evaluation of her polyps revealed regenerative (inflammatory) pseudopolyps, rather than true adenomatous polyps recorded in some earlier descriptions of patients with this syndrome. This is the first report of the association of Cronkhite-Canada syndrome with multiple myeloma.

A 47-yr-old patient with primary biliary cirrhosis and multiple sclerosis is reported. Although primary biliary cirrhosis has been associated with numerous other autoimmune disorders, it has not, to the authors' knowledge, previously been reported in association with multiple sclerosis.

In one patient, an epithelioid cell nevus of the conjunctiva contained numerous large, unpigmented, mononucleated, binucleated, and multinucleated benign-appearing nevus cells with abundant cytoplasm and frequent intranuclear vacuoles. Despite their overall size, the cells manifested a low nuclear-cytoplasmic ratio. After a partial excision of the lesion, the remainder spontaneously regressed during a two-year period. Another patient's lesion was dominated by a proliferation of spindle nevus cells developing in a long-standing epibulbar nevus. The spindle cells were moderately pigmented, frequently located within walls of epithelial inclusion cysts, and had benign cytologic features. Finally, in a third patient with the cutaneous B-K mole syndrome, a dysplastic conjunctival nevus developed that featured intraepithelial, atypical melanocytic proliferation with superficial colonization of the substantia propria. This portion coexisted with a deeper, preexistent lesion in the substantia propria that was comprised of orderly nests of unpigmented cuboidal nevus cells surrounded by pigmented, spindle-shaped blue nevus cells--a so-called "mixed nevus."

A detailed evaluation of the clinical and histologic manifestations of eosinophilic fasciitis is described in a 22-year-old woman. Scleroderma-like skin involvement is associated with eosinophilia and hypergammaglobulinemia. Visceral and serologic manifestations of a generalized scleroderma are lacking. Results of a biopsy showed severe thickening of the deep fascia accompanied by an infiltration of lymphocytes and plasma cells. This syndrome must be differentiated from generalized scleroderma because eosinophilic fascitis has a benign course and may benefit from systemic corticosteroid therapy.

Two patients with bullous systemic lupus erythematosus are reported. In one, the disease appears to have been caused by hydralazine. The cutaneous lesions of bullous SLE have not been previously reported in drug-induced lupus.

This report describes a patient with a drug reaction and histologic changes of both eosinophilic cellulitis and eosinophilic pustular folliculitis. We propose that some cases of eosinophilic pustular folliculitis, like eosinophilic cellulitis, may occur as a result of a hypersensitivity phenomenon.

Five male patients with infertility due to biopsy-proven germinal cell aplasia were given a 100-microng bolus of luteinizing hormone (LH)/follicle-stimulating hormone (FSH)-releasing hormone (LRH), and the resultant LH, FSH, and testosterone responses were correlated with their histologic patterns on testicular biopsy. The basal and stimulated FSH values were elevated in four of five patients. Basal LH values were elevated in three patients, while two clearly had exaggerated LH and testosterone responses to LRH. Although there was little correlation between various parameters, elevated basal LH values were associated with Leydig cell hyperplasia. Higher basal FSH levels were present when fibrosis and complete aplasia of germinal elements were found in the same biopsy specimen, and the magnitude of the FSH response to LRH correlated positively with the basal concentration. The findings of elevated basal LH values, an exaggerated LH response to LRH, lack of testosterone response, and Leydig cell hyperplasia indicate a definite disturbance of the LH-testosterone axis in many patients with germinal cell aplasia. Therefore, the regulation of secretion of both gonadotropins appears to be abnormal in this disorder.