Epiluminescence microscopy for the diagnosis of doubtful melanocytic skin lesions. Comparison of the ABCD rule of dermatoscopy and a new 7-point checklist based on pattern analysis

OBJECTIVE: To compare the reliability of a new 7-point checklist based on simplified epiluminescence microscopy (ELM) pattern analysis with the ABCD rule of dermatoscopy and standard pattern analysis for the diagnosis of clinically doubtful melanocytic skin lesions. DESIGN: In a blind study, ELM images of 342 histologically proven melanocytic skin lesions were evaluated for the presence of 7 standard criteria that we called the "ELM 7-point checklist." For each lesion, "overall" and "ABCD scored" diagnoses were recorded. From a training set of 57 melanomas and 139 atypical nonmelanomas, odds ratios were calculated to create a simple diagnostic model based on identification of major and minor criteria for the "7-point scored" diagnosis. A test set of 60 melanomas and 86 atypical nonmelanomas was used for model validation and was then presented to 2 less experienced ELM observers, who recorded the ABCD and 7-point scored diagnoses. SETTINGS: University medical centers. PATIENTS: A sample of patients with excised melanocytic lesions. MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the models for diagnosing melanoma. RESULTS: From the total combined sets, the 7-point checklist gave a sensitivity of 95% and a sepcificity of 75% compared with 85% sensitivity and 66% specificity using the ABCD rule and 91% sensitivity and 90% specificity using standard pattern analysis (overall ELM diagnosis). Compared with the ABCD rule, the 7-point method allowed less experienced observers to obtain higher diagnostic accuracy values. CONCLUSIONS: The ELM 7-point checklist provides a simplification of standard pattern analysis because of the low number of features to identify and the scoring diagnostic system. As with the ABCD rule, it can be easily learned and easily applied and has proven to be reliable in diagnosing melanoma.     

Processed electroencephalogram during combined extradural and general anaesthesia

BACKGROUND: The usual methods of scabies diagnosis include microscopic identification of the mites and their eggs and feces in skin scrapings. In many cases, the results of microscopic examination can be negative owing to the low number of parasites present in the cornified layer. Epiluminescence microscopy (ELM) is an in vivo technique that allows a detailed inspection of the skin, from the surface to the superficial papillary dermis. This is where the scabies mite lives. In this study, we evaluate the applicability and the usefulness of ELM for in vivo diagnosis of scabies. OBSERVATIONS: Sixty-five (93%) of 70 cases of scabies showed small, dark, triangular structures at the sites examined with ELM. A subtle linear segment seen below the base of the triangle was made visible by the presence of small air bubbles. Together, both structures resembled a jet with contrail. On traditional microscopic examination of the scrapings, we verified that the triangular structure corresponded to the pigmented anterior section of the mite in all cases. The linear segment observed on ELM was thought to be the burrow of the mite along with its eggs and fecal pellets. The cases in which the results of a first ELM examination were negative demonstrated positive results on a second ELM examination carried out 20 days later. CONCLUSION: Epiluminescence microscopy is a very useful tool for in vivo diagnosis of scabies because it permits Sarcoptes scabiei detection in only a few minutes, with no discomfort to the patient and with a very low number of false-negative results.     

Spectroscopic analysis of biliary calculi: correlations of the type of calculi and clinical data of 25 consecutive surgical patients

The Authors considering cholelithiasis as an heterogenic pathological entity report their experience of 25 surgical consecutive patients: 20 with cholesterol or combination gallstones and 5 with black pigmented gallstones. In this series the most frequent factors associated with cholesterol gallstones were LDL hypercholesterolemia and hypertriglyceridemia; while the most frequent factors associated with black pigmented gallstones were hepatopathies. The most frequent symptom was dyspepsia. Only the black pigmented and the mixed gallstones were associated with jaundice and pancreatitis. According to the Literature infection is associated to brown pigment gallstones in 95% of cases, in this series infection is rarely associated with other types of gallstones. Treatment with oral bile salts is useful only in pure cholesterol gallstones, so the distinction among different types of gallstones is useful not only for a better knowledge of their pathogenesis but also for a correct choice of the therapeutic options.     

Bronchiolo-alveolar cell carcinoma with apparent response to chemotherapy to anti-tuberculosis

Pigmented vulvar lesions were observed in a child during a sexual abuse evaluation. Gross examination of the lesions appeared most consistent with bowenoid papulosis; however, biopsy confirmed the lesions to be pigmented apocrine hamartomas. To our knowledge, these rare and benign tumors have never been described as pigmented, but should be added to the differential diagnosis of pigmented vulvar lesions.     

Differences in black pigmentation in lepidopteran cuticles as revealed by light and electron microscopy

Black cuticles of larvae and pupae from various Lepidoptera were studied by light and electron microscopy. There are striking differences in the representation of black pigmentation, especially at the ultrastructural level. Two types may be described: 1. With the light microscope black melanin-like grana, electron-dense electron microscopically, are found in the distal parts of the exocuticle. This type is demonstrated in larvae of Celerio euphorbiae, Papilio machaon, and Phalera bucephala. 2. With the light microscope, a dark homogeneous layer in the distal exocuticle can be recognized, however, electron microscopically no structures correlated with this dark pigment layer. This type of pigmentation was present in pupae of Pieris brassicae and Aglais urticae; in Pieris larvae the dark pigmented layer appeared to be limited to the epicuticle. In Celerio processes of the epidermal cells are involved in transporting precursors to the exocuticle. The conclusion was reached that black pigmentation in cuticles is based on different mechanisms as proposed by structural features. The two likely mechanisms are melanization and sclerotization.     

Intraepidermal bile pigment in skin biopsy specimens for graft-versus-host disease versus erythema multiforme

The differentiation of graft-verus-host disease (GVHD) from erythema multiforme (EM) presents a common diagnostic challenge in skin biopsy specimens from patients who have received patients allogeneic bone marrow transplants. The presence of gastrointestinal involvement might be the only way to make a diagnosis of GVHD in these cases. In the absence of liver function tests, gastrointestinal biopsy, or molecular techniques such as microsatellite DNA analysis, the presence of intraepidermal bile pigment might prove helpful in elucidating hyperbilirubinemia and allowing a pathologist to favor a diagnosis of GVHD over EM. Routinely processed archival tissue from 50 cases of GVHD (42 Caucasian and 8 of unknown race) and 50 cases of EM (31 Caucasian and 19 of unknown race) was examined for pigmentation. Intraepidermal pigmentation was stained for bile pigment and melanin. Among the intraepidermal EM lesions, 4 (8%) stained for intracorneal melanin, but none stained for bile pigment. Among the intraepidermal GVHD lesions, 8 (16%) stained for intracorneal melanin, but 3 (6%) stained for intracorneal bile pigment. In addition, 13 (26%) GVHD lesions and 9 (18%) EM lesions showed melanosis with melanin in all layers of the epidermis as well as within papillary dermal melanophages. Thus, when presented with a differential diagnosis of GVHD versus EM, the presence of intraepidermal bile pigment might suggest liver involvement and a diagnosis of GVHD.     

Dynamics of cell-associated viremia and antibody response during the early phase of lentivirus infection in sheep

OBJECTIVE: To investigate the characteristic epiluminescent microscopic features of early lesions of malignant melanoma affecting glabrous skin, which is the most prevalent site of the neoplasm in nonwhite populations. DESIGN: The epiluminescent microscopic features of various kinds of melanocytic lesions affecting glabrous skin were investigated using a videomicroscope. All the diagnoses were determined clinically and histopathologically using the standard criteria. SETTING: A dermatology clinic at a university hospital. PATIENTS: The following 130 melanocytic lesions consecutively diagnosed at our department were examined: 16 lesions of acral lentiginous melanoma, 6 lesions of malignant melanoma in situ, and 108 lesions of benign melanocytic nevus (acquired or congenital). MAIN OUTCOME MEASURE: The incidence of each characteristic epiluminescent feature was compared among disease categories. RESULTS: On epiluminescent microscopy, malignant melanoma in situ and the macular portions of invasive malignant melanoma showed accentuated pigmentation on the ridges of the skin markings, which are arranged in parallel patterns on glabrous skin. This "parallel ridge pattern" was found in 5 (83%) of 6 lesions of malignant melanoma in situ and in 15 (94%) of 16 lesions of malignant melanoma. The parallel ridge pattern was rarely found in the lesions of benign melanocytic nevus. Most benign melanocytic nevi showed 1 of the following 3 typical epiluminescent patterns: (1) a parallel furrow pattern exhibiting pigmentation on the parallel sulci of [he skin markings (54%), (2) a latticelike pattern (21%), and (3) a fibrillar pattern showing filamentous or meshlike pigmentation (15%). The remaining 11 benign nevi (10%) showed a nontypical pattern. CONCLUSION: Because epiluminescent microscopic features of early malignant melanoma on glabrous skin are characteristic, we can effectively detect early lesions using this noninvasive method.     

Prominent pigmented fungiform papillae of the tongue

Prominent pigmented fungiform paillae of the tongue are characterized clinically by prominence and pigmentation confined to these papillae and histopathologically by melanophages in the lamina opriae. A 45-year-old Asian woman had dark erythematous papules exclusively involved with fungiform papillae on the anterior lateral dorsal aspect of the tongue and hyperpigmentation on the lip. Histologic examination revealed many melanophages in the subepidermal area within the fungiform papillae. Her skin lesions improved moderately following two months of treatment for anemia.     

Pigmented lesions in newborn infants

1058 newborn infants were examined. Forty-one (3-9%) had clinically discernible pigmented lesions compatible with melanocytic naevi. Biopsy was performed on thirty-four of the forty-one and of these; eleven, representing 1-01% of the infants, proved to be melanocytic naevi. No giant (garment) naevi were seen in this series. Two of the eleven naevi pathologically examined showed histological changes similar to those that have been reported in some giant naevi, but the remaining nine were not only different from criteria usually assigned to giant naevi, but they also differed from the usual adult naevi, in that most were predominantly junctional. None of the melanocytic naevi in this series showed any suggestion of malignant change. In newborn infants it is often impossible clinically to distinguish naevi from other types of pigmented lesions, as only eleven out of the thirty-four pigmented lesions were melanocytic naevi. Seven of the eleven melanocytic naevi were under 1-5 cm in diameter. No pigmented lesions were found on the palms, soles or genitalia.     

Laser applications in dermatology

Over the past decades continuous wave laser systems have been used in dermatology for the photocoagulation and vaporization of vascular neoformations and malformations and to remove epithelial lesions. However, their mainly thermal effect can have negative impact on wound healing and scar formation due to thermal damage of adjacent tissue. More recent laser systems now permit more selective and more restrictive destruction of pathological tissue. They include pulsed and Q-switched lasers matched to the absorption characteristics of the target structures, which permit skin ablation and selective photothermolosysis of pigmented or vascular lesions. These technical innovations have expanded the therapeutic spectrum in dermatology and improved the quality of the results achieved. Nevertheless, these systems should be used only for carefully selected indications, in particular when corrective-aesthetic considerations are of importance. Furthermore, prior to treatment, it is mandatory for the dermatologist, to establish the proper diagnosis, especially in the case of pigmented lesions and skin changes of uncertain dignity.     

Diagnosing basal cell carcinoma by dermatoscopy

BACKGROUND: Dermatoscopy (DS) has been used primarily to evaluate pigmented skin lesions. Little information is available on DS findings of basal cell carcinoma (BCC). Dermatoscopy is a noninvasive technique that allows visualization of cutaneous features from the skin surface to the papillary dermis. Basal cell carcinoma, the most common cutaneous malignancy, is traditionally diagnosed clinically and confirmed with biopsy. OBJECTIVE: To determine the dermatoscopic features of nonpigmented basal cell carcinomas. Methods: The dermatoscopic findings of 27 lesions that clinically were suspicious for BCC were analyzed. RESULTS: Of these 27 clinically suspect lesions, the biopsies revealed BCC in 20 specimens and squamous cell carcinoma (SCC) in two specimens. Twenty of these 22 specimens had dermatoscopic findings of BCC: diffusely distributed, branching blood vessels, asymmetric, and narrow blood vessels distributed deeper in the dermis, or a milky-red corona with superficial wide blood vessels. One nodular BCC in our study showed no distinct findings. CONCLUSIONS: Many BCCs have characteristic DS findings; however, dermatoscopic examination of some tumours will not demonstrate any known characteristic findings. As such, the DS criteria we propose for BCC are best utilized as an adjunctive study of clinical impressions. Biopsy remains the definitive diagnostic tool.     

The incorporation of drugs into hair: relationship of hair color and melanin concentration to phencyclidine incorporation

Rodents with different hair pigmentation patterns were studied to evaluate the role of melanin in the incorporation of phencyclidine (PCP) into hair. There are two types of melanin in hair and other tissues: eumelanin, a brown-black pigment and pheomelanin, a reddish-yellow pigment. Sprague Dawley (SD; nonpigmented), Dark Agouti (DA; brown), Copenhagen (CP; brown hooded), Long Evans (LE; black hooded), and LBNF1 (deep brown) rats and Swiss-Webster (SW; nonpigmented), C57BL6 (black), and C57BL6 Ay/a (yellow) mice were administered PCP at 10 mg/kg/day for 5 days (n = 5 for each strain). Hair was collected either 14 (rats) or 35 (mice) days (mice) after beginning drug administration and analyzed for PCP, eumelanin, and pheomelanin. PCP concentrations in ng/mg (mean +/- SEM) were as follows: SD, 0.46 +/- 0.13; DA, 12.25 +/- 1.24; CP nonpigmented, 0.12 +/- 0.004; CP pigmented, 9.16 +/- 2.8; LE nonpigmented, 0.66 +/- 0.07; LE pigmented, 21.2 +/- 1.4; LBNF1, 21.64 +/- 3.8; SW, 0.48 +/- 0.36; C57 black, 11.0 +/- 4.03; and C57 yellow, 2.26 +/- 0.55. Eumelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 20.50 +/- 1.58; CP pigmented, 19.43 +/- 0.40; LE pigmented, 17.56 +/- 0.61; LBNF1, 27.26 +/- 2.52; C57 black, 37.33 +/- 3.61; and C57 yellow, 1.76 +/- 0.02. Eumelanin was not detected in nonpigmented hair. Pheomelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 0.09 +/- 0.00; CP pigmented, 0.20 +/- 0.03; LBNF1, 0.06 +/- 0.01; C57 black, 0.16 +/- 0.05; and C57 yellow, 29.16 +/- 0.97. Pheomelanin was not detected in nonpigmented or LE pigmented hair. These data demonstrate that PCP is incorporated into black hair to a greater extent than yellow or nonpigmented hair. There appears to be a linear relationship between the PCP concentration in hair and the ratio of eumelanin to pheomelanin. Our data suggest that despite variations in PCP concentration because of hair color, they may be normalized by using the ratio of eumelanin to pheomelanin rather than hair weight.     

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.     

Survival analysis in patients with cutaneous malignant melanoma

INTRODUCTION: Cutaneous malignant melanoma (MM) takes only 3% of all malignant tumours of the skin, but for reason of its increased frequency and pronounced tendency to rapid growth and metastases, it causes 60% of total lethal outcomes due to malignant tumours of the skin [1]. Primary MM is a diagnostic problem because of the great variety of its clinical features. Asymmetric configuration, irregular border, speckled color(r)diameter of more than 6 mm, and elevation of the surface, suggest suspicion of malignant alteration, but even then misdiagnosis is possible. For the final diagnosis of MM histopathological confirmation is necessary. The method to use is the extensive excisional biopsy of the lesion and its borders [2]. Histopathological diagnosis is based on microscopic findings which include: histogenetic type of MM, tumour thickness according to Breslow, level of invasion according to Clark, presence of ulceration, grade of lymphocyte infiltration, mitote rate, type of cells, presence of melanin in cells [2, 3]. PATIENTS AND METHODS: A five-year survival of patients with cutaneous malignant melanoma (MM) was studied according to sex, age and distinct features of the tumour: site, type of initial therapy, stage of the disease, time from the first signs of the disease to diagnosis of MM, histological findings (histogenetic type, Breslow's tumour thickness, Clark's level of invasion, presence of ulceration, degree of lymphocyte infiltration, number of mitoses, type of cells, intensity of pigmentation) and presence of metastases. The retrospective study included 336 patients with cutaneous MM. There were 185 female (55.1%) and 151 male patients (44.9%), aged 14-83 years, mean age 48.8 years, who were treated at the institute of Oncology and Radiology in Belgrade from 1978 to 1990. The mean follow-up was 60 months (1-144 months). Melanoma in situ had 16 (4.1%) patients. Stage I had 45 patients (14.1%), stage II 163 (48.5%), stage III 83 (24.7%) and stage IV 29 (8.6%) patients. Acral location on hands and feet had 40 (11.9%) patients, on head and neck 36 (10.7%), on the trunk 146 (43.5%) and on the extremities (except hands and feet) 114 (33.9%) patients. Nodular melanoma (NM) was the most frequent histogenetic type revealed in 150 (44.6%) patients, superficial spreading melanoma (SSM) in 105 (31.1%) patients, acral melanoma (AM) in 39 (11.5%) and lentigo malignant melanoma (LMM) in 32 (9.4%) patients (Table 1). Five-year survival rate was calculated according to Kaplan-Meier's method and significance of the difference between some categories was tested by Long-Rank's test; the significance less than 0.05 was accepted. RESULTS: Statistically highly significant differences in a five-year survival (p < 0.01) were related to sex p = 0.0005, age p = 0.0017, tumour site p = 0.0025, initial therapy p = 0.0036, stage of MM p = 0.0000, histological features of the tumour p = 0.0000 and presence of metastases p = 0.0000. A better five-year survival prognosis was found in female patients (64.5%) compared to male patients 44.5%, aged 27-46 years (87.3%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (66.7%) compared to patients younger than 26 years (43.5%); patients with melanoma on the extremities (except hands and feet) had a better five-year survival (65.7%) compared to patients with melanoma on the trunk or acral melanoma (47.3%). Higher survival was recorded in the group of patients with the tumour 1.5-3 mm thick, in whom the tumours was excised and regional nodes dissected as the primary therapy (66.9%) compared to those who underwent excision of the tumor only (48.8%). A five-year survival of patients with MM in situ was 100% for those in stage I; 85% in stage II; 42% in stage III, 16% and 0% in stage IV. The patients in whom the diagnosis of MM was established within 10 months after the first signs of the disease had significa     

Recognizing neoplastic skin lesions: a photo guide

Malignant lesions of the skin are common. Patients who develop squamous cell carcinoma and malignant melanoma often have recognizable precursor conditions. A few skin lesions resemble malignancies. Lesions that are growing, spreading or pigmented, or those that occur on exposed areas of skin are of particular concern. Knowing the similarities and differences between these lesions allows the primary physician to make a diagnosis in most cases by simple inspection and palpation. When in doubt, it is appropriate to perform an excisional biopsy of small lesions or punch biopsy of larger lesions. Removal of premalignant lesions will reduce the occurrence of malignant disease. Almost all skin cancers can be cured by early excision or destruction. For these reasons, physicians should be aware of the risk factors for skin cancer, educate patients about risk reduction and include skin inspection for premalignant and malignant lesions as a part of routine health maintenance examinations.     

Interobserver variability on the histopathologic diagnosis of cutaneous melanoma and other pigmented skin lesions

PURPOSE: To assess the interobserver agreement on the diagnosis and classification of cutaneous melanoma. MATERIALS AND METHODS: A set of 140 slides of cutaneous melanoma, including a small subset of benign pigmented skin lesions, were circulated to four experienced histopathologists. The kappa statistic for multiple ratings per subject was calculated using the method described by Fleiss. RESULTS: The kappa value on the diagnosis of cutaneous melanoma versus benign lesions was 0.61. There was some discordance on the diagnosis in 37 of 140 cases (26%). For the histopathologic classification of cutaneous melanoma, the highest kappa values were attained for Breslow thickness (kappa = 0.76) and presence of ulceration (kappa = 0.87). The agreement was generally poor for other histologic features, such as level of dermal invasion (kappa = 0.38), presence of regression (kappa = 0.27), and lymphocytic infiltration (kappa = 0.27). CONCLUSION: Our study suggests considerable disagreement among pathologists on the diagnosis of melanoma versus other pigmented lesions. Tumor thickness and presence of ulceration are the most reproducible histologic features of cutaneous melanoma.     

DNA-based HLA class II postmortem typing: evaluation of different techniques for prospective corneal allografting

BACKGROUND: Two new types of lasers, the pulsed dye laser and the Q-switched ruby laser, have shown good to excellent results in the treatment of vascular malformations and benign pigmented lesions of the skin. A new and very effective alternative to pulsed dye laser is the recently introduced Photoderm VL. This device is based on the use of a wide-band non-coherent intense pulsed light source which emits a continuous spectrum in the range of 515 nm to 1200 nm. PATIENTS AND METHODS: More than a 1000 patients with a variety of lesions of the skin were treated by these new laser systems and the Photoderm VL. The Q-switched ruby laser (wavelength 694 nm, pulse duration 25 ns) is suitable for the treatment of benign lentigines, café-au-lait macules, seborrhoic ceratosis, tattoos, and traumatic tattoos. The pulsed dye laser (585 nm, 0,3-0,45 ms) treats nevi flammei, capillary hemangiomas, telangiectasias, xanthelasma, hypertrophic scarring, and adenoma sebaceum. In addition we present the facilities of the new Photoderm VL (515 nm-1200 nm, 0,5-20 ms) for the treatment of nevi flammei, benign hemangiomatous malformations, telangiectasias, erythrosis interfollicularis colli, hypertrophic scarring, and hypertrichosis. RESULTS AND CONCLUSIONS: the Q-switched ruby laser, the pulsed dye laser, and the Photoderm VL show excellent results in the treatment of lesions of the skin, which otherwise would have been difficult to treat of untreatable. The efficiency of the laser types presented is based on the theory of selective photothermolysis. Scarring is almost never seen and hypo- or hyperpigmentation is in most cases transient.     

Morphologic diversity in malignant melanoma: the potential use of microdissection and the polymerase chain reaction for diagnosis

Malignant melanoma (MM) can mimic soft tissue (ST) and epithelial neoplasms. An immunoperoxidase (IP) panel and a morphologic comparison of the primary are used in diagnosis, which can be difficult when the morphologic and IP profiles of a metastatic lesion simulate those of an ST neoplasm. Through the comparison of known genetic abnormalities in primary and metastatic neoplasms, a definitive diagnosis can be suggested on the basis of the finding of identical allelic losses through the use of microdissection (MD) and the polymerase chain reaction (PCR). Genetic alterations involving the p16 gene on chromosome 9p21 have been observed in MM. We present the case of a 56-year-old man with known MM in whom multiple metastatic lesions to the skin and an adrenal gland developed during a 5-year period. A fine-needle aspiration (FNA) of a new ST buttock lesion was performed; the specimen had cytologic features different from those of the primary neoplasm and simulated a possible primary ST neoplasm. We attempted to make a definitive diagnosis of MM in the FNA of the ST buttock lesion through a genetic comparison with the primary neoplasm as well as with the other metastatic sites. Direct-visualization MD was performed on histologic glass slides of the primary and adjacent tissue (normal control), and the metastatic lesions, along with malignant cell clusters from the buttock lesion FNA. DNA was extracted and PCR amplified with primers D9S171 and IFNA for the p16 locus at the 9p21-22 region. Loss of heterozygosity for the D9S171 marker at the p16 gene locus was identified in all of the neoplastic tissue tested. Normal skin elements did not show deletion. The combination of MD and PCR are powerful tools that can be used for the comparison of genetic abnormalities in primary and metastatic neoplasms with unusual morphologic features to help support a diagnosis with a noncontributory IP.     

Chromogranin A: its clinical value as marker of neuroendocrine tumours

Pigmentation is a well recognised adverse effect of minocycline therapy. Various body sites, most notably the skin, nails, bones, thyroid, mouth and eyes are affected and the pigmentation may appear at multiple sites. In general, pigmentation results from long term administration of minocycline at cumulative doses greater than 100 g, although cutaneous or oral mucosal pigmentation may appear, regardless of dose or duration of therapy. When the skin is involved, the blue-black pigmentation develops most frequently on the shins, ankles and arms. Other patterns of skin involvement include pigmentation that is either generalised and symmetrical, or that develops at sites of inflammation. The bones of the oral cavity are probably the most frequently affected sites of pigmentation affecting greater than 20% of patients taking minocycline for more than 4 years. In contrast, the oral mucous membranes and teeth are infrequently pigmented from minocycline. Ocular, thyroid and visceral pigmentation is also relatively uncommon and usually develops only with high doses and long term minocycline use. Whereas pigmentation of the skin and oral mucosa is generally reversible when the drug is discontinued, the pigmentation is often permanent when other sites are involved. Although minocycline-induced pigmentation is not harmful, the drug should be discontinued when the adverse effect is recognised. All patients receiving minocycline, especially those treated for longer than 1 year, require screening for the development of pigmentation.