Myogenic tremor - a novel tremor entity.

PURPOSE OF REVIEW: Tremor is a common neurological symptom with a plethora of potential etiologies. Apart from physiological tremor, the vast majority of tremor syndromes are linked to a pacemaker in the central nervous system (CNS) or, less common, in the peripheral nervous system. Myogenic tremor is a novel tremor entity, first reported in 2019 and believed to originate in the muscle itself. In this review, we describe the clinical properties of myogenic tremor and discuss its presumed pathogenesis on the basis of all of the patient cases published so far. RECENT FINDINGS: Myogenic tremor manifests itself as a high frequency, postural, and kinetic tremor with onset in infancy. To date, only myopathies affecting the contractile elements, in particular myosin and a myosin-associated protein, have been recognized to feature myogenic tremor. The generator of the tremor is believed to be located in the sarcomere, with propagation and amplification of sarcomeric oscillatory activity through CNS reflex loops, similar to neuropathic tremor. SUMMARY: True myogenic tremor must be distinguished from centrally mediated tremor due to myopathies with central nervous system involvement, i.e., mitochondrial myopathies or myotonic dystrophies. The presence of myogenic tremor strongly points toward a sarcomere-associated mutation and may thus be a valuable clinical tool for the differential diagnosis of myopathies.

Disseminated inflammation of the central nervous system associated with acute hepatitis E: a case report.

BACKGROUND: Hepatitis E infection affects over 20 million people worldwide. Reports of neurological manifestations are largely limited to the peripheral nervous system. We report a middle-aged genotype 3c male patient with acute hepatitis E virus (HEV) infection and severe neurological deficits with evidence of multiple disseminated inflammatory lesions of the central nervous system. CASE PRESENTATION: A 42-year-old male patient presented to our emergency department with musculoskeletal weakness, bladder and bowel retention, blurred vision and ascending hypoesthesia up to the level of T8. Serology showed elevated liver enzymes and positive IgM-titers of hepatitis E. Analysis of cerebrospinal fluid (CSF) showed mild pleocytosis and normal levels of glucose, lactate and protein. HEV-RNA-copies were detected in the CSF and stool. Within 3 days after admission the patient became paraplegic, had complete visual loss and absent pupillary reflexes. MRI showed inflammatory demyelination of the optic nerve sheaths, multiple subcortical brain regions and the spinal cord. Electrophysiology revealed axonal damage of the peroneal nerve on both sides with absent F-waves. Treatment was performed with methylprednisolone, two cycles of plasma exchange (PLEX), one cycle of intravenous immunoglobulins (IVIG) and ribavirin which was used off-label. Liver enzymes normalized after 1 week and serology was negative for HEV-RNA after 3 weeks. Follow-up MRI showed progressive demyelination and new leptomeningeal enhancement at the thoracic spine and cauda equina 4 weeks after admission. Four months later, after rehabilitation was completed, repeated MRI showed gliotic transformation of the spinal cord without signs of an active inflammation. Treatment with rituximab was initiated. The patient remained paraplegic and hypoesthesia had ascended up to T5. Nevertheless, he regained full vision. CONCLUSIONS: Our case indicates a possible association of acute HEV infection with widespread disseminated central nervous system inflammation. Up to now, no specific drugs have been approved for the treatment of acute HEV infection. We treated our patient off-label with ribavirin and escalated immunomodulatory therapy considering clinical progression and the possibility of an autoimmune response targeting nerve cell structures. While response to treatment was rather limited in our case, detection of HEV in patients with acute neurological deficits might help optimize individual treatment strategies.

Rediscovery of Otto Frank's contribution to science.

In the late 19th century, German physiologist Otto Frank (1865-1944) embarked on a near life-long research program of laying down the mathematical, methodological, and theoretical foundations in order to understand and define the performance of the heart and circulatory system in all their complexity. The existence of the "Frank-Starling law" testifies to this. Two of his seminal publications have been translated into English previously, introducing Frank's research on the dynamics of the heart and the arterial pulse to a wider audience. It is likely that there are a host of other comparable achievements and publications of Frank that are still unknown to the international scientific (cardiological and physiological) community. However, their influence can still be felt and seen in modern cardiology and cardio-physiology, such as in the development of modern interactive simulating and teaching programs. We have translated and commented on ten of these papers, which can be read in parallel with the German originals. These publications show a wealth of theoretical assumptions and projections regarding the importance of the sarcomere, the development of models of contraction, thermo-dynamical considerations for muscular activity, differences between cardiac and skeletal muscles, problems related to methodology and measurement, and the first pressure-volume diagram (published 120 years ago). These topics were envisioned by Frank long before they became a focus of subsequent modern research. Nowadays, frequent measurements of pressure-volume relationships are made in research using the pressure-volume conductance catheter technique. In commenting Frank's scientific topics, we try to show how interconnected his thinking was, and thus how it enabled him to cover such a wide range of subjects.

Imaging mass spectrometry assists in the classification of diagnostically challenging atypical Spitzoid neoplasms.

BACKGROUND: Previously, using imaging mass spectrometry (IMS), we discovered proteomic differences between Spitz nevi and Spitzoid melanomas. OBJECTIVE: We sought to determine whether IMS can assist in the classification of diagnostically challenging atypical Spitzoid neoplasms (ASN), to compare and correlate the IMS and histopathological diagnoses with clinical behavior. METHODS: We conducted a retrospective collaborative study involving centers from 11 countries and 11 US institutions analyzing 102 ASNs by IMS. Patients were divided into clinical groups 1 to 4 representing best to worst clinical behavior. The association among IMS findings, histopathological diagnoses, and clinical groups was assessed. RESULTS: There was a strong association between a diagnosis of Spitzoid melanoma by IMS and lesions categorized as clinical groups 2, 3, and 4 (recurrence of disease, metastases, or death) compared with clinical group 1 (no recurrence or metastasis beyond a sentinel node) (P < .0001). Older age and greater tumor thickness were strongly associated with poorer outcome (P = .01). CONCLUSIONS: IMS diagnosis of ASN better predicted clinical outcome than histopathology. Diagnosis of Spitzoid melanoma by IMS was strongly associated with aggressive clinical behavior. IMS analysis using a proteomic signature may improve the diagnosis and prediction of outcome/risk stratification for patients with ASN.

Reassessing Diagrams of Cardiac Mechanics: From Otto Frank and Ernest Starling to Hiroyuki Suga.

This article explores the importance of diagrams in the history of the understanding of cardiac function, by comparing Ernest Starling's famous "Law of the Heart" (1918) with the mathematically based view of cardiac mechanics put forward by Otto Frank (1897). Whereas Frank's diagrams gained influence in German cardio-physiological publications, they were widely unknown abroad until 1969, when Hiroyuki Suga began to present similar approaches for warm-blooded animals as Frank had done for the frog. Suga succeeded in correlating the pressure volume area (PVA)-a composite of Frank's work loop plus the area of remaining potential energy-with the oxygen consumption of the beating heart. With the concept of time-varying elastance as an index of cardiac contractility, Suga's approach became attractive for clinical applications, and Daniel Burkhoff and colleagues were able to use these insights for real-time, interactive simulations of the cardiovascular system. Such tools can be used for exploring basic hemodynamic principles and, thanks to technical developments of miniature pumps within the same time frame (Καιρός, the "right moment," or "the opportune"), to test the effects of device-based treatment for heart failure. These outcomes confirm that old analyses of the heart's activity may still be useful today.

Evaluation of heart involvement in calpainopathy (LGMD2A) using cardiovascular magnetic resonance.

INTRODUCTION: Cardiac dysfunction occurs in several forms of limb girdle muscular dystrophy (LGMD). The aim of this study was to investigate cardiac involvement in calpainopathy (LGMD2A). METHODS: Cardiovascular evaluation was performed in 10 patients with genetically verified LGMD2A by echocardiography, 3 Tesla - cardiovascular magnetic resonance, 24-h electrocardiography recordings with heart rate variability (HRV) analysis, and 24-h blood pressure recordings. RESULTS: No patient with calpainopathy showed impairment of left or right ventricular function. One patient had a small amount (2% of left ventricle mass) of late gadolinium enhancement. HRV analysis revealed no significant difference compared with external reference data. CONCLUSIONS: The main finding of this study is the lack of cardiac involvement in patients with calpainopathy. Cardiac involvement was not found, even in individuals with advanced age and greater disease severity. Furthermore, we did not observe an overall reduction of cardiac autonomic regulation in calpainopathy.

The diagnostic value of midbrain hyperechogenicity in ALS is limited for discriminating key ALS differential diagnoses.

BACKGROUND: Hyperechogenicity of the substantia nigra was recently reported in patients with sporadic ALS with a frequency similar to PD. Data on the diagnostic utility compared to key differential diagnoses of ALS do not exist yet. METHODS: We prospectively enrolled 43 patients with ALS, 29 with myasthenia gravis, 25 patients with inflammatory neuropathy, and 13 with cervical canal stenosis. All patients were examined by a blinded investigator using transcranial B-mode sonography planimetrically measuring hyperechogenic areas of the midbrain representing the substantia nigra. RESULTS: Mean midbrain hyperechogenic area was increased in ALS compared to non-ALS differentials. ROC analysis revealed only small area under the curve for detecting ALS (AUC: 0.669 [95%CI: 0.56-0.78]; p = 0.006). Highest Youden index was observed for area size of <0.14 cm(2) (Youden index: 0.28). Using this cut-off score and that generated from normative data of healthy controls, area size measurements provided a sensitivity of only 46-58% and specificity of 69-83% for detecting ALS. No correlations of hyperechogenic area sizes in ALS patients were found to age, gender, ALS subtype (bulbar versus spinal form), disease duration or ALS-FRS-R score. CONCLUSIONS: Midbrain hyperechogenicity is reproducibly found in ALS patients, but its diagnostic value for discriminating ALS from its key differentials is limited.

Immunolabeling for p16, WT1, and Fli-1 in the assignment of growth phase for cutaneous melanomas.

Distinction between radial growth phase (RGP) and vertical growth phase (VGP) in cutaneous melanomas is prognostically significant. Despite established morphological criteria, molecular markers to separate RGP and VGP have not been well established. The goal of this study was to investigate associations of p16, WT1, and Fli-1 with RGP-to-VGP progression, by immunohistochemistry. The p16 is a tumor suppressor, whereas WT1 and Fli-1 are transcriptional activators. The authors hypothesized that entry into VGP would be associated with decreased p16 and increased WT1 and Fli-1. Paraffin sections from 18 RGP and 15 VGP melanomas were immunostained with well-characterized antibodies to p16, WT1, and Fli-1. Melanoma growth phases were determined using precodified morphological attributes. In RGP melanomas, p16 was expressed in 15 of 18 (83%), WT1 in 17 of 17 (100%), and Fli-1 at least focally in 6 of 18 (33%). The deep dermal component of VGP melanomas stained positively for Fli-1 in 9 of 14 (64%), strongly for WT1 in 10 of 14 (71%), and strongly for p16 in only 2 of 15 (13%). Observed patterns of WT1 immunopositivity did not support the authors' hypothesis; it is not likely to be a good indicator of VGP. On the other hand, Fli-1 staining trended toward more positive deep tumor compartment staining and p16 to weaker staining in the deep compartment. At present, application of histological criteria remains the best method for assignment of growth phase in melanomas; however, p16 and possibly Fli-1 immunostains may serve as useful adjuncts in morphologically indeterminate cases.

CD20+ mycosis fungoides: a report of three cases and review of the literature.

Mycosis fungoides (MF) is the most common of the family of cutaneous T-cell lymphomas, accounting for 65% of all cases of cutaneous T-cell lymphomas. The classic phenotypic profile is one defined by CD4+ T cells showing a reduction in the expression of CD7 and CD62L. There are 3 previous reports describing CD20 expression in MF. The cell surface antigen CD20 is a transmembrane glycosylated phosphoprotein expressed in the early stages of B-cell development before differentiation into plasma cells. Two male patients, aged 14 and 44 years, presented with persistent truncal plaques up to 8 cm of 1 and 4 years duration, respectively. A third patient, an 80-year-old female, presented with a 1-year history of progressive nodules involving the head and neck area. Cases 1 and 2 both responded to topical treatment modalities. The biopsies in cases 1 and 2 showed features typical of plaque stage MF, whereas case 3 was compatible with follicular MF with tumor stage transformation. Phenotypically, the aberrant cell populace demonstrated a CD4+, CD7-, and CD62L- phenotype; at variance with classic MF was the expression of CD20. Although there were a few PAX5-positive staining cells, definitive colocalization studies were negative. Other B-cell markers and heavy chain immunoglobulin rearrangement were not detected. There are a growing number of reports describing T-cell lymphomas and leukemias with CD20 expression. Of the 6 CD20+ MF cases reported in the literature to date, 3 have been associated with a more aggressive clinical course; all but one case have occurred in males.

The origin of the heartbeat and theories of muscle contraction. Physiological concepts and conflicts in the 19th century.

The origin of the incessant rhythmical heartbeat and the mechanism of muscle contraction have fascinated scientists over centuries. This short review outlines physiological explanations that were discussed in the 19th century starting with Albrecht von Haller (1708-1777), an 18th century physiologist who proposed that the heart has an intrinsic irritability. He argued that under normal conditions the inflow of blood stimulates the heart muscle to contract by mechanical touch and distension. Johannes Müller (1800-1858, physiologist in Bonn and Berlin) contended that the influence of the sympathetic nerve, specifically the activity of intracardiac ganglia, is the foremost cause of the heartbeat. Walter H. Gaskell and Theodor Engelmann (physiologists in Cambridge and Utrecht, respectively) independently criticized this neurogenic theory. They reported experimental evidence that supported the myogenic theory of the origin of the heartbeat, which has been accepted since about 1900. The concept of cardiac mechano-sensitivity, which can be traced back to A. von Haller, is currently resurging. Concerning mechanisms of contraction, Edward A. Schäfer (1850-1935), histologist and physiologist in Edinburgh, described differences between cardiac and skeletal muscle and coined the term sarcomere. Based on microscopic studies of cross-striated muscle, Schäfer outlined a detailed and plausible mechanism of muscle contraction in 1892. He put forward that during muscle shortening the "clear part of the muscle substance" (actin) might pass into longitudinal canals, which exist between the "sarcous elements" (myosin). His model foresaw fundamental elements of the sliding filament model, which was discovered by the Huxleys about 60 years later.

Serum Neurofilament Light Chain: A Marker of Nervous System Damage in Myopathies.

Purpose: Neurofilament light chain in serum (sNfL) has been suggested as a biomarker for the assessment of neuroaxonal damage. Since NfL are not expressed in muscle, elevated sNfL in patients with primary myopathies suggest additional nervous system involvement. To verify this hypothesis, we measured sNfL in a series of patients with myopathies. Methods: sNfL were determined in 62 patients with molecular proven primary myopathies in whom some nervous system involvement may be predicted: myotonic dystrophy type I and II (DM I, II) and mitochondrial disease. In addition, sNfL were measured in 8 patients with facioscapulohumeral muscular dystrophy (FSHD) and in a disease control group caused by genetic defects exclusively expressed in muscle. Results: sNfL values were significantly elevated in the DM I, the DM II and the mitochondrial group, with FSHD patients showing the lowest sNfL elevations. sNfL levels in the disease control group were not different from the healthy controls. A significant correlation between repeat length and sNfL levels was found in the DM I patients, but not in the DM II patients. Mitochondrial patients with encephalopathy showed significantly higher sNfL concentrations compared to patients with only muscular symptoms. Conclusion: sNfL levels are elevated in myopathies with, based on the underlying molecular defect or clinical features, established nervous system involvement, i.e., myotonic dystrophies and mitochondrial disorders. sNfL were also raised in FSHD, where involvement of the nervous system is not usually clinically apparent. Thus, sNfL concentrations may serve as a biomarker for additional neuronal damage in primary myopathies.

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis.

BACKGROUND: Melanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells. METHODS: During and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments. RESULTS: Mature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3+ cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers. CONCLUSIONS: A multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3+T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00705640.

Cutaneous CD4+ CD56+ hematologic malignancies.

BACKGROUND: Hematologic malignancies expressing CD4 and CD56 are most commonly associated with the recently described CD4(+) CD56(+) hematodermic neoplasm. METHODS: Thirteen cases of CD4(+) CD56(+) hematologic malignancies were prospectively encountered in the routine and referral practices of the authors. RESULTS: Patients 1 and 2 were elderly men exhibiting an acute onset of skin, bone-marrow, and peripheral blood involvement, both dying of their disease within less than 12 months. CD3(+) phenotype and a clonal T-cell receptor beta rearrangement indicated categorization as a CD4(+) natural killer T-cell lymphoma. Patient 3 developed a CD56(+) anaplastic large cell lymphoma and is without disease after excision and radiation. Indolent CD4(+) CD56(+) poikilodermatous mycosis fungoides defined case 4. There were 7 patients with CD123(+) CD4(+) CD56(+) hematodermic neoplasm, 4 dying within 18 months of presentation with peripheral blood/marrow involvement in 6 of the 7 cases. Two patients with granulocytic sarcoma dying within 100 days of presentation defined the last two cases. LIMITATIONS: There were relatively small numbers in each of the categories and the follow-up was limited in those cases where death was not reported. CONCLUSION: Cutaneous malignancies composed of CD4(+) CD56(+) hematopoietic cells define a varied group and oftentimes have an aggressive clinical course although not in every case.

ADCK2 Haploinsufficiency Reduces Mitochondrial Lipid Oxidation and Causes Myopathy Associated with CoQ Deficiency.

Fatty acids and glucose are the main bioenergetic substrates in mammals. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data showed that Adck2+/- mice exhibited impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in Coenzyme Q (CoQ) biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.

Atypical lymphocytic lobular panniculitis: a clonal subcutaneous T-cell dyscrasia.

BACKGROUND: Atypical lymphocytic lobular panniculitis (ALLP) is a recently described entity characterized by waxing and waning plaques. A morphologic and biologic continuum with subcutaneous panniculitis-like T-cell lymphoma has been suggested. METHODS: Between 2003 and 2007, we encountered five patients with ALLP. Comprehensive phenotypic and molecular studies were performed using multiplex polymerase chain reaction. RESULTS: The patient population comprised four women, one man and two boys, age range of 6-42 years. All patients had a similar clinical presentation, being one of the recurrent infiltrative plaque-like lesions. All cases showed a permeation of the interstitial spaces of the subcutis by well-differentiated lymphocytes unaccompanied by significant fat necrosis. Molecular studies showed a clonal and/or oligoclonal profile in all cases. In all cases in which multiple biopsies were obtained, there was preservation of the identical T-cell clonotypes at different biopsy sites and over time. No patient progressed to lymphoma. One patient achieved remission with isotrentinoin. CONCLUSIONS: ALLP represents a form of cutaneous lymphoid dyscrasia given the relatively self-limited nature of the eruption, albeit in the context of clinical recurrence.

Prominent eosinophilic intranuclear inclusions in melanocytes of a melanocytic nevus: the aftermath of an infection with molluscum contagiosum? A case report.

A 65-year-old Latino man presented to his dermatologist for the removal of two melanocytic nevi from the back. The first nevus was removed from the right scapula and contained melanocytes with prominent eosinophilic nuclear inclusion bodies. The second nevus was removed from the paravertebral region, without evidence of inclusion bodies. Ultrastructurally, the inclusions in the first nevus contained dispersed finely granular, homogenous bodies without a limiting membrane. Immunohistochemistry characterized them as ubiquitin-positive material. Reverse transcriptase in situ polymerase chain reaction analysis was positive for molluscum-specific primers, suggesting that the inclusions encountered in the first nevus were secondary to a remote, local molluscum viral infection of melanocytes.

Terbinafine-induced dermatomyositis: a case report and literature review of drug-induced dermatomyositis.

Dermatomyositis, a connective tissue disease syndrome where antibodies to the endothelium of the microvasculature of the skin, muscle and lung are implicated in lesional propagation, is characterized by photodistributed erythema, heliotrope rash, Gottron's papules, muscle weakness and interstitial pulmonary fibrosis. Endotheliotropic viruses and underlying neoplasia are among the inciting triggers. Uncommon drugs, namely the lipid-lowering agents, have been implicated in dermatomyositis. The patient, a 57-year-old man, developed a photodistributed rash and muscle weakness following treatment with the antifungal medication, terbinafine. A skin biopsy was performed, showing an atrophying interface dermatitis with pandermal mucinosis and striking vasculopathic changes including endothelial cell necrosis with denudement and basement membrane zone reduplication. Ultrastructural studies confirmed the presence of endothelial cell injury. Direct immunofluorescent testing showed prominent staining of C5b-9 along the dermal-epidermal junction and within the vasculature. Western blot studies showed strong seroreactivity of his serum to an endothelial-based protein weighing 45,000, a common target described in other microvascular injury-based syndromes. We have shown a temporal association between use of terbinafine and the development of dermatomyositis. The exact basis remains speculative. One potential hypothesis is based on the fact that terbinafine, the active agent in terbinafine, triggers apoptosis of human endothelial cells in culture. Enhanced endothelial cell apoptosis results in the displacement of various cellular antigens creating a state of neoantigenicity; its attendant sequelae is held to be one of anti-endothelial cell antibody formation, a defining pathogenetic event in the evolution of dermatomyositis. The second may be because of the effects of the drug on the promotion of an interferon-rich T-helper-1-dominant cytokine milieu.

Cutaneous manifestation of disseminated strongyloidiasis in a patient coinfected with HTLV-I.

Strongyloidiasis is a potentially lethal parasitic infection. Coinfection of a patient with human T-lymphotropic virus type I (HTLV-I) can lead to a more severe disease course and treatment-refractoriness. Here we report a patient coinfected with HTLV-I and Strongyloides stercoralis who developed disseminated, treatment-resistant disease. The patient presented with serpiginous, nonpalpable, purpuric streaks on the abdomen and proximal lower extremities. A biopsy of this eruption demonstrating filariform larvae in the dermis was consistent with disseminated strongyloidiasis. The patient's immune dysregulation due to HTLV-I positivity likely contributed to her development of disseminated disease. Awareness of the interaction between HTLV-I and strongyloidiasis has important implications in terms of prognosis and treatment. Recognition of the cutaneous manifestations of disseminated disease can facilitate diagnosis and implementation of appropriate therapy.

Pigmented purpuric dermatosis: classification by phenotypic and molecular profiles.

The categorization of pigmented purpuric dermatosis (PPD) as a form of cutaneous lymphoid dyscrasia has been suggested. Phenotypic and molecular studies were done on 43 patients with PPD. The molecular studies used a capillary gel electrophoresis T-cell receptor beta multiplex polymerase chain reaction assay. There were 2 principal categories: polyclonal PPD represented by 22 cases and monoclonal variants comprising 21 cases. Monoclonal cases had extensive skin lesions. An identical restricted T-cell repertoire independent of time and location was observed. Approximately 40% of the monoclonal cases had clinical and pathologic features of mycosis fungoides (MF). In the polyclonal variant, disease outside the lower extremities was uncommon; there were no patients with MF. Striking reductions in CD7 and CD62L were seen in both groups. PPD is a form of cutaneous T-cell lymphoid dyscrasia, based on the frequency of monoclonality, the preservation of persistent T-cell clonotypes, and extent of pan-T-cell marker loss. Stratification of lesions of PPD according to the molecular profile may be of significant value prognostically and influence therapeutic intervention.