Solitary epidermolytic acanthoma: a clinical and histopathological study.

BACKGROUND: Epidermolytic acanthoma (EA) is an uncommon cutaneous entity that typically presents as a solitary lesion, or, less commonly, as multiple or disseminated discrete lesions. It usually appears at or after middle-age, and has been reported in various locations including the face, trunk, extremities and genitalia. Histopathologically, EA shows epidermolytic hyperkeratosis (EHK) involving either the entire thickness of the epidermis or just the granular and upper spinous layers. OBJECTIVE AND METHODS: To describe the clinical and microscopic features of EA, we retrospectively reviewed all cases diagnosed as EA at the Skin Pathology Laboratory at Boston University between 1999 and 2009. RESULTS: Solitary EA is more common in men (65%) and usually presents as a hyperkeratotic papule on the trunk (45%) or extremities (25%). Histopathologically, all cases of solitary EA showed the classical features of hyperkeratosis, acanthosis and EHK. Three architectural patterns were observed on scanning magnification: papillomatous (55%), cup-shaped (40%) and acanthotic (15%). Additional common features encountered included focal parakeratosis (85%), and a sparse to mild superficial perivascular lymphocytic infiltrate (90%). CONCLUSION: This large case series of solitary EA reviews the clinical features of this entity and describes several new histological variants.

Temporal triangular alopecia with decreased follicular density.

Temporal triangular alopecia (TTA) is a type of alopecia that is often congenital, and clinically exhibits hair loss on one or both temples. It is characterized histologically by a normal number of small hair follicles without significant inflammation. We report a patient with TTA whose biopsy exhibited a decreased number of hair follicles. There are limited reports of the histopathology of TTA, and most have utilized standard vertical sections. Of the handful of patients with transversely sectioned biopsies, follicular numbers have been reportedly normal. Our finding of a patient with TTA with a decreased number of hair follicles broadens the histologic spectrum of this disorder, and may have implications for pathogenesis.

Cicatricial marginal alopecia: is it all traction?

BACKGROUND: In a specialized hair loss clinic, a group of patients was identified with focal or complete hair loss at the scalp periphery, with a normal scalp surface. Biopsy revealed complete loss of individual hair follicles, indicative of scarring alopecia. Not all patients had a history supportive of a diagnosis of traction alopecia. OBJECTIVES: To identify and characterize further patients with scarring alopecia of the scalp margin using a retrospective review. METHODS: All biopsies of scarring alopecia carried out by a single clinician between 1 January 1999 and 29 September 2006 were reviewed. Patients in whom the hair loss was located at the periphery of the scalp were selected for retrospective chart review. RESULTS: A total of 15 patients met the study criteria, which included histological scarring alopecia and hair loss of the scalp margin. Six of the patients gave a history of relaxing or straightening their hair. Six denied hair care practices sufficient to cause traction alopecia. In three patients, the hair care history was unknown. Occipital hair loss was a common clinical finding, mimicking alopecia areata. The presence of scarring was often subtle histologically. CONCLUSIONS: A group of patients with moderate to severe cicatricial alopecia of the scalp margin is described. The presence of scarring is difficult to diagnose both clinically and histologically. The lack of a history of severe traction or harsh styling practices in half the patients casts doubt on whether or not traction is the only pathogenic factor.

Atypical pilar leiomyoma: cutaneous counterpart of uterine symplastic leiomyoma?

Four cases of cutaneous leiomyoma with cytologic atypia are reported. All four cases were adult men ranging in age from 33 to 92 years of age. Clinical diagnoses were diverse and included epidermal inclusion cyst, scar, nevus, dermatofibroma, squamous cell carcinoma, and basal cell carcinoma. Histological examination of all four lesions revealed a relatively circumscribed, mild to focally moderately cellular, dermal proliferation of large, irregularly shaped spindle cells in a fascicular arrangement. Some cells contained large irregular nuclei and abundant cytoplasm; others were multinucleate. Moderate to focal marked pleomorphism and rare mitotic figures were present, raising the possibility of leiomyosarcoma; however, the sparse mitotic activity and low cellularity did not warrant this diagnosis. This study suggests that cutaneous leiomyomas may exhibit bizarre or "symplastic" patterns analogous to their uterine counterparts.

Gianotti-Crosti syndrome presenting as lichenoid dermatitis.

Papular acrodermatitis of childhood (Gianotti-Crosti syndrome) is an uncommon, self-limited disease characterized by an erythematous papular eruption symmetrically distributed on the face and limbs and mild lymphadenopathy, thought to be of viral origin. The histopathologic findings are nonspecific and include focal parakeratosis, mild spongiosis, superficial perivascular infiltrate, papillary dermal edema, and extravasated red blood cells. Interface changes with some basal vacuolization may be present, but are not a conspicuous feature. We present a 2 1/2-year-old boy with multiple papules and plaques on the face and extremities and cervical lymphadenopathy. Histopathologic analysis showed compact orthokeratosis, focal parakeratosis, hypergranulosis, psoriasiform epidermal hyperplasia, and a dense lichenoid lymphohistiocytic infiltrate with extensive exocytosis of mononuclear cells. Immunoperoxidase staining with CD 1 a revealed clusters of Langerhans cells in the epidermis and in the papillary dermis. In view of the clinical findings, a diagnosis of Gianotti-Crosti syndrome was made. Although there are a few reports describing a lichenoid pattern of infiltration in Gianotti-Crosti syndrome, this histologic pattern is not widely known. This case is presented to illustrate the fact that Gianotti-Crosti syndrome can present as lichenoid dermatitis, and, especially in children, should be added to the differential diagnoses of lichenoid infiltrates.

Is it lymphoma or lymphomatoid papulosis?

Distinguishing malignancy from premalignant conditions can be difficult. Controversy surrounds both the clinical and histologic criteria used to distinguish lymphomatoid papulosis, a benign disorder, from CD30+ anaplastic large-cell lymphoma. Three case histories illustrate important points in categorizing different lymphoproliferative disorders as benign or malignant. We emphasize a multidisciplinary approach to improve diagnosis and patient management.

Neuropharmacological mechanisms underlying rhythmical discharge in trigeminal interneurons during fictive mastication.

1. We have examined the effects of iontophoretic application of antagonists to excitatory amino acid (EAA) receptors, as well as glycine and gamma-aminobutyric acid (GABA), on rhythmically active (RA) brain stem neurons during cortically induced masticatory activity (RMA) in the anesthetized guinea pig. Ten of these neurons were antidromically activated at latencies of 0.3-0.9 ms by stimulation of the trigeminal motor nucleus (MoV). 2. RA neurons were divided into closer and opener type according to the phase of activation during RMA. Iontophoretic application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a specific non-N-methyl-D-aspartate (NMDA) receptor antagonist, suppressed discharge of both closer and opener type RA neurons during RMA. In contrast, iontophoretic application of 3-((1)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), a specific NMDA receptor antagonist, was not effective in suppressing discharge of most opener type RA neurons but did reduce activity of closer type RA neurons. 3. Spike discharge of most RA neurons was time locked to each cortical stimulus during RMA. Some of the RA neurons were activated at a short latency to short pulse train stimulation of the cortex in the absence of RMA. In most cases CNQX reduced such time-locked responses during RMA and greatly reduced discharge evoked by short pulse stimulation of the cortex in all cases. In contrast, CPP was not as effective in suppressing either the time-locked responses during RMA or the discharge evoked by short pulse train stimulation of the cortex. 4. D,L-Homocysteic acid (HCA) application produced low level maintained discharge in RA neurons before RMA induction. When RMA was evoked in combination with HCA, rhythmical burst discharges with distinct interburst periods during the opening phase of RMA were observed in most closer type RA neurons. In contrast, during RMA in combination with HCA application, opener type RA neurons showed burst discharges that were modulated during the RMA cycle but lacked distinct interburst periods during the closer phase of the cycle. 5. During application of strychnine (STR), a glycine antagonist, discharge of closer type RA neurons increased in the opener phase of RMA during continuous HCA application. In contrast, bicuculline methiodide (BIC), a GABA antagonist, did not increase unit discharge of closer type RA neurons in the opener phase of RMA. 6. It is concluded that closer type RA neurons receive, alternatively, EAA-mediated excitatory and glycine-mediated inhibitory masticatory synaptic drive signals during RMA.(ABSTRACT TRUNCATED AT 400 WORDS)

Giant cell lichenoid dermatitis: a possible manifestation of sarcoidosis.

Giant cell lichenoid dermatitis is a recently described dermatosis thought to be an unusual lichenoid drug eruption. It is characterized by a generalized, pruritic, papulosquamous eruption sparing palms, soles, face and mucous membranes. Histopathologic findings include areas of epidermal hyperplasia and atrophy with focal vacuolar alteration of the basal layer, exocytosis and cytoid body formation. The dermis contains a band-like, mononuclear cell infiltrate at the dermoepidermal junction with admixed eosinophils, plasma cells and large multinucleate cells. The histologic differential diagnosis includes infectious processes, sarcoidosis, lichen nitidus, lupus erythematosus and lichen planus. We report 3 patients with giant cell lichenoid dermatitis, one of whom was subsequently diagnosed as having sarcoidosis. Because giant cell lichenoid dermatitis may resemble sarcoidosis both clinically and histologically, and because cutaneous sarcoid is often associated with systemic involvement, the diagnosis of sarcoid should be strongly considered in patients with giant cell lichenoid dermatitis.

Electrophysiological properties of guinea pig trigeminal motoneurons recorded in vitro.

1. Intracellular recording and stimulation were made from guinea pig trigeminal motoneurons (TMNs) in brain stem slices. Electrophysiological properties were examined and the underlying currents responsible for motoneuron excitability were investigated by the use of current clamp and single electrode voltage clamp (SEVC) techniques. 2. The voltage responses to subthreshold hyperpolarizing or depolarizing current pulses showed voltage- and time-dependent inward rectification. SEVC analysis demonstrated that the hyperpolarizing inward rectification resulted from the development of a slowly occurring voltage-dependent inward current activated at hyperpolarized membrane potentials. This current persisted in solutions containing low Ca2+/Mn2+, tetraethylammonium (TEA), and Ba2+, whereas it was reduced by 1-3 mM cesium. The depolarizing inward rectification was mediated by a persistent sodium current (INa-P) that was completely abolished by bath application of tetrodotoxin (TTX). 3. Action potential characteristics were studied by intracellular stimulation with brief current pulses (< 3 ms) in combination with ionic substitutions or application of specific ionic conductance blocking agents. Bath application of TTX abolished the action potential, whereas 1-10 mM TEA or 0.5-2 mM 4-aminopyridine (4-AP) increased, significantly, the spike duration, suggesting participation of the delayed rectifier and A-current type conductances in spike repolarization. SEVC analysis revealed a TEA-sensitive sustained outward current and a fast, voltage-dependent, transient current with properties consistent with their roles in spike repolarization. 4. TMN afterhyperpolarizing potentials (AHPs) that followed a single spike consisted of fast and slow components usually separated by a depolarizing hump [afterdepolarization (ADP)]. The fast component was abolished by TEA or 4-AP but not by Mn2+, Co2+, or the bee venom apamin. In contrast, the slow AHP was readily reduced by Mn2+, Co2+, or apamin, suggesting participation of an apamin-sensitive, calcium-dependent K+ conductance in the production of the slow AHP. SEVC analysis and ionic substitutions demonstrated a slowly activating and deactivating calcium-dependent K+ current with properties that could account for the slow AHP observed in these neurons. 5. Repetitive discharge was examined with long depolarizing current pulses (1 s) and analysis of frequency-current plots. When evoked from resting potential (about -55 mV), spike onset from rheobase occurred rapidly and was maintained throughout the current pulse. At higher current intensities, early and late adaptations in spike discharge were observed. Frequency-current plots exhibited a bilinear relationship for the first interspike interval (ISI) in approximately 50% of the neurons tested and in most neurons tested during steady-state discharge (SS).(ABSTRACT TRUNCATED AT 400 WORDS)

Hanlester Laboratories decision: how is it affected by new sanctions and penalties regulations?

The following excerpts from the briefs recently submitted to Administrative Law Judge (ALJ) Stephen Kessel in the Hanlester Laboratories administrative proceeding, deal with the applicability of a January 29, 1992 final rule on fraud and abuse sanctions and civil money penalties (57 Fed. Reg. 3,298 (January 29, 1992) to the case. Counsel for Hanlester Laboratories, Patric Hooper and W. Bradley Tully of Hooper, Lundy & Bookman, Inc. in Los Angeles, argue that the Office of the Inspector General (OIG-HHS) is trying to change the rules "well after the game has been played," and that this "is obviously being done for the sole purpose of negating the rights" of the Hanlester respondents. The Office of the General Counsel (OGC), in a brief prepared by OGC attorney Larry J. Goldberg, contends that ALJ Kessel "must apply these regulations in rendering his decision," arguing that the "regulations at issue do not even involve a change in policy, but merely a clarification." The Hanlester case (The Inspector General v. Hanlester Network et al., No. C-448 (Department of Health and Human Services, Departmental Appeals Board, Civil Remedies Division) was remanded by the Departmental Appeals Board to ALJ Kessel on September 18, 1991. It is the first case to consider the application of the antikickback statute to a joint venture, and is the first HHS civil exclusion case to be brought as the result of allegations of violations of the antikickback statute (see HealthSpan, November 1991, p. 8).

Genioglossus EMG activity during rhythmic jaw movements in the anesthetized guinea pig.

The electromyograph (EMG) activity of the left anterior digastric and the genioglossus muscles was studied in ketamine-anesthetized guinea pigs under 3 separate jaw movement paradigms. The first paradigm has been previously named spontaneous rhythmic jaw movements. These jaw movements occur 1-2 h after the onset of ketamine anesthesia. After spontaneous rhythmic jaw movements began, a single dose of apomorphine caused a new, second jaw movement paradigm to occur, apomorphine-induced rhythmic jaw movements. The final paradigm, cortically-evoked rhythmic jaw movements, was elicited by electrical stimulation of the masticatory area of the cerebral cortex. Genioglossus EMG activity was complex and highly variable in spontaneous rhythmic jaw movements; however, apomorphine-induced jaw movements were characterized by simultaneously occurring rhythmic EMG bursts of approximately 230 ms duration in both the digastric and genioglossus muscles. In 4 of 5 animals, genioglossus muscle activity onset preceded digastric muscle activity onset by approximately 20 ms. These results support the hypothesis that apomorphine-induced rhythmic jaw movements are an analog of lapping in the awake animal. In cortically-evoked rhythmic jaw movements, both digastric and genioglossus EMG activity were time-locked to the cortical electrical stimulation, with an onset latency of approximately 11 ms for the digastric EMG activity and of 16 ms for the genioglossus EMG activity. These results support the hypothesis that both trigeminal and hypoglossal motoneuron pools are closely coupled in certain coordinative movement patterns.

Effect of Herpes simplex virus infection on the trigeminal jaw-opening reflex in guinea pigs.

Herpes simplex virus (HSV) infection induces numerous electrophysiological and microscopic changes in neurons in vitro. To investigate the effect of HSV infection on in vivo neuronal activity, we induced an acute, latent and reactivated HSV infection of the trigeminal ganglia of guinea pigs through orofacial HSV inoculation and studied its effect on the trigeminal jaw-opening reflex of anesthetized guinea pigs. During the acute viral infection period both the threshold for elicitation of the reflex, and the latency to the onset of the reflex response were increased. During the latent viral infection in the trigeminal ganglia, the jaw-opening reflexes in the viral infected animals were not different from those of non-infected control animals. However, reactivation of the latent viral infection in these animals resulted in increases in both the threshold and latency of the jaw-opening reflex. These changes were similar to those found in animals with the acute viral infection. These results indicate that acute or reactivated latent HSV infection of the nervous system results in functional changes in the reflex pathways involving the trigeminal gasserian ganglia and brainstem neurons harboring infectious HSV-1.

Porokeratosis arising in a burn scar.

A histologically verified porokeratosis arose in a burn scar on the back of a 47-year-old man. This phenomenon has not been previously reported. We discuss the literature on porokeratosis, the relation between epidermal and dermal injury, and the genesis of this lesion.

The effects of nanoliter ejections of lidocaine into the pontomedullary reticular formation on cortically induced rhythmical jaw movements in the guinea pig.

In the ketamine/urethane anesthetized guinea pig, electromyographic (EMG) responses of the anterior digastric muscle were studied when loci within the lower brainstem were microejected with lidocaine (2%) during rhythmical jaw movements (RJMs) evoked by repetitive electrical stimulation of the masticatory area of the cortex. The area investigated was between the trigeminal motor nucleus (Mot V) and the rostral pole of the inferior olive. Microejections of lidocaine, contralateral to the cortical stimulus site, into the ventral-medial portion of Mot V where digastric motoneurons are known to be located, resulted in reduction or complete abolishment of the digastric EMG activity ipsilateral to the ejection with no effective change in mean cycle duration (CD) or mean percent normalized integrated amplitude of the contralateral digastric EMG. Microejections of lidocaine, contralateral to the cortical stimulus site, into the ponto-medullary reticular formation in areas that included portions of the caudal nucleus pontis caudalis (PnC), nucleus gigantocellularis (GC), medial nucleus parvocellularis (PCRt), and dorsal paragigantocellularis (dPGC), in most cases produced a bilateral reduction in the mean normalized integrated amplitude and a bilateral increase in the mean cycle duration. In these sites, the bilateral increase in mean cycle duration of digastric EMG bursts was also associated with a significant increase of coefficient of variation in CD. In many cases, microejection of lidocaine completely abolished rhythmical digastric activity, bilaterally. HRP injections into Mot V were performed to determine the locations of trigeminal premotoneurons and their relationship to effective lidocaine sites for rhythmical jaw movement suppression. Retrogradely labeled cells were found mainly in the mesencephalic nucleus of V; trigeminal principal and spinal V sensory nuclei, bilaterally; and within the intermediate and lateral regions of reticular formation, bilaterally. No labeling was found in the medial reticular formation, including the nucleus gigantocellularis and dorsal paragigantocellularis.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracellular analysis of trigeminal motoneuron rhythmical activity during stimulation of pontomedullary reticular formation in anesthetized guinea pig.

1. The effects of repetitive stimulation of the nucleus pontis caudalis and nucleus gigantocellularis (PnC-Gi) of the reticular formation on jaw opener and closer motoneurons were examined. The PnC-Gi was stimulated at 75 Hz at current intensities less than 90 microA. 2. Rhythmically occurring, long-duration, depolarizing membrane potentials in jaw opener motoneurons [excitatory masticatory drive potential (E-MDP)] and long-duration hyperpolarizing membrane potentials [inhibitory masticatory drive potentials (I-MDP)] in jaw closer motoneurons were evoked by 40-Hz repetitive masticatory cortex stimulation. These potentials were completely suppressed by PnC-Gi stimulation. PnC-Gi stimulation also suppressed the short-duration, stimulus-locked depolarizations [excitatory postsynaptic potentials (EPSPs)] in jaw opener motoneurons and short-duration, stimulus-locked hyperpolarizations [inhibitory postsynaptic potentials (IPSPs)] in jaw closer motoneurons, evoked by the same repetitive cortical stimulation. 3. Short pulse train (3 pulses; 500 Hz) stimulation of the masticatory area of the cortex in the absence of rhythmical jaw movements activated the short-latency paucisynaptic corticotrigeminal pathways and evoked short-duration EPSPs and IPSPs in jaw opener and closer motoneurons, respectively. The same PnC-Gi stimulation that completely suppressed rhythmical MDPs, and stimulus-locked PSPs evoked by repetitive stimulation to the masticatory area of the cortex, produced an average reduction in PSP amplitude of 22 and 17% in jaw closer and opener motoneurons, respectively. 4. PnC-Gi stimulation produced minimal effects on the amplitude of the antidromic digastric field potential or on the intracellularly recorded antidromic digastric action potential. Moreover, PnC-Gi stimulation had little effect on jaw opener or jaw closer motoneuron membrane resting potentials in the absence of rhythmical jaw movements (RJMs). PnC-Gi stimulation produced variable effects on conductance pulses elicited in jaw opener and closer motoneurons in the absence of RJMs. 5. These results indicate that the powerful suppression of cortically evoked MDPs in opener and closer motoneurons during PnC-Gi stimulation is most likely not a result of postsynaptic inhibition of trigeminal motoneurons. It is proposed that this suppression is a result of suppression of activity in neurons responsible for masticatory rhythm generation.

An analysis of mandibular movement trajectories and masticatory muscle EMG activity during drinking in the guinea pig.

Electromyographic (EMG) activity of the anterior digastric, lateral pterygoid, and deep masseter muscles as well as the associated jaw movements during drinking were studied in the awake guinea pig. Drinking was characterized by rhythmic, vertically directed jaw movements with little or no associated lateral movements. The jaw opening phase of each cycle was associated with bilaterally synchronized EMG activity in the digastric and lateral pterygoid muscles, and the jaw closing phase with bilaterally synchronized activity in the masseter muscles. The mean EMG burst durations (+/- 1 S.E.) in the digastric and masseter muscles were 164.2 +/- 14.93 ms and 94.3 +/- 26.44 ms, respectively. The digastric muscle EMG burst duration was significantly correlated with drinking cycle time and with masseter muscle EMG onset; on the other hand, masseter muscle EMG burst duration was not correlated with cycle time. These patterns of EMG activity and jaw movement trajectories are similar to those induced by apomorphine in the ketamine-anesthetized guinea pig.

Angiotensin II-induced rhythmic jaw movements in the ketamine-anesthetized guinea pig.

The EMG activity of the left anterior digastric muscle as well as associated jaw movements were studied in ketamine-anesthetized guinea pigs that had received i.v. infusions of angiotensin II (ANG-II). Rhythmic jaw movements with two distinct movement profiles were associated with ANG-II infusion. One movement profile was typified by vertical jaw opening and closing movements with little or no associated horizontal movement. The second rhythmical jaw movement profile was unlike the first in that jaw closing was accompanied by a significant horizontal deflection of the jaw. Both jaw movement profiles were similar in that little or no horizontal movement occurred during jaw opening. Tongue protrusions were also observed during jaw opening in both cases. The results show that ANG-II induces rhythmic jaw movements in anesthetized guinea pigs. ANG-II-induced jaw movement profiles and digastric muscle EMG activity are similar to those seen after an i.v. injection of apomorphine in the anesthetized guinea pig, and to those associated with lapping in the awake animal.