Michael B. Morgan

Lethal Non-Langerhans Cell Histiocytoses: Necrobiotic Xanthogranuloma and Xanthoma Disseminatum

The histiocytic disorders encompass a broad range of malignant and nonmalignant entities capable of presenting in a variety of clinical and pathologic guises. The histiocytic disorders are generally classified by the cell of the origin, and specifically as bone marrow tissue-derived monocytes that migrate secondarily to the skin serving as either phagocytic macrophages or antigen-presenting dendritic or Langerhans cells. Langerhans cells typically reside closely to the epithelium and traffic to the lymph nodes. They are important in immunologic surveillance and are defined by the presence of Birbeck granules on ultrastructural examination, as well as S-100 and CD-1a immunopositivity. This discussion will focus upon the entities composed of the phagocytic non-Langerhans cell macrophages and specifically the disorders within this category capable of producing or being associated with significant morbidity or mortality.

Gyrate Erythemas: Erythema Gyratum Repens and Erythema Chronicum Migrans

The gyrate erythemas are a heterogeneous group of dermatoses clinically defined by the presence of circinate, annular, and/or polycyclic lesions that are often associated with serious underlying systemic diseases. The gyrate erythemas consist of the entities erythema annulare centrifugum (EAC), erythema marginatum rheumaticum (EMR), erythema gyratum repens (EGR), and erythema chronicum migrans (ECM). The latter two entities, namely, EGR and ECM, are associated with potentially deadly underlying disorders and thus will be discussed in greater detail.

Pemphigus Vulgaris and Paraneoplastic Pemphigus

The disease pemphigus encompasses a group of related blistering conditions characterized by circulating antibodies against keratinocyte cell surface antigens important in mediating cell-to-cell adhesion (Becker and Gaspari, Dermatol Clin, 1993;11:429; Lever. J Am Acad Dermatol. 1979;1:2). Of the various types and forms of the disease including pemphigus foliaceus, pemphigus erythematosus, IgA pemphigus, and pemphigus vegetans, it is pemphigus vulgaris (PV) and paraneoplastic pemphigus (PP) that constitute the most important causes of mortality. Overall, these disorders are quite rare, with an estimated prevalence of between 1 in 100,000 for PV and less than 1 in 1,000,000 for PP. Both disorders are seen principally in aged adults with a near equal gender distribution. PV is more commonly observed among Jews and individuals of Mediterranean descent, whereas there is no known ethnic predilection for PP.

Acquired Ichthyosis, Acanthosis Nigricans, and Palmar Hyperkeratosis

Serious systemic diseases, including visceral cancer, may be indirectly signaled by the development of distinctive cutaneous eruptions. Important aspects of these eruptions include the development of the rash concurrent with the diagnosis of the neoplasm and the fact that the two entities, though individually uncommon, are commonly seen together and pursue a similar clinical course. The more important, albeit uncommon, dermatoses that develop in conjunction with visceral cancer involve disorders of the epithelium and entail alterations in keratinization. This chapter will deal with the clinical and pathologic attributes of acquired ichthyosis, acanthosis nigricans (AN), and paraneoplastic palmar/plantar keratoderma as they relate to underlying malignancy.

Rocky Mountain Spotted Fever and Rickettsioses

Rickettsioses constitute a diverse group of arthropod-borne human diseases capable of producing significant morbidity and mortality. They share important pathologic and clinical attributes that permit their diagnosis in most instances (Zaki. NY State J Med. 1989;89:320). Rickettsioses are responsible for a great number of deaths seen particularly in times of war. It is estimated that over three million combatants and civilians in the First World War succumbed to epidemic typhus. Among the more deadly types of infection belonging to this group is Rocky Mountain spotted fever, the principal subject of this chapter.

Life-threatening Lymphomas and Leukemias with Prominent Cutaneous Involvement

Primary cutaneous gamma–delta T-cell lymphoma (PCGDTCL) is a rare condition, the details of which have come into focus in dermatologic and oncologic literature in the last 25 years. The effector cell is an activated gamma–delta T cell with a cytotoxic phenotype. This entity represents 1 % of cutaneous T-cell lymphomas and 10 % of peripheral T-cell lymphomas. It is classified as a provisional entity in the category of peripheral T-cell lymphomas, unspecified by the World Health Organization and European Organisation for Research and Treatment of Cancer (WHO-EORTC) [1]. Unfortunately, those stricken with this disorder have a poor prognosis, with rapid progression of disease and average survival of 15 months [2].

Necrolytic Migratory Erythema

Necrolytic migratory erythema (NME) is a major component of glucagonoma syndrome, a rare paraneoplastic syndrome consisting of the classic triad of diarrhea, diabetes mellitus, and rash associated with serum hyperglucagonemia. Originally described by Becker et al. in 1942, NME has an incidence of approximately 1 in 20 million. There is no ethnic or gender predilection, and peak age of onset is during the fourth and fifth decades. NME occurs in 70 % of those with glucagonoma syndrome. Glucagonomas are associated with type 1 multiple endocrine neoplasia (MEN I) syndrome sequence and/or Zollinger-Ellison hypergastrinemia syndrome in a minority of the cases (about 5 % of cases). The most common etiology involves the elaboration of glucagon from an islet cell tumor of the pancreas but may rarely follow the metabolic consequences of cirrhosis, pancreatic insufficiency, or celiac disease.

Lethal Hereditary Vascular Disorders: Osler-Weber-Rendu Syndrome, Ataxia-Telangiectasia, and Fabry’s Disease

Mucocutaneous vascular ectasia, otherwise referred to as telangiectasia, can be an important harbinger of serious systemic disease. Among a variety of acquired conditions, including hepatic cirrhosis, that are responsible for their development, are a heterogeneous group of inherited conditions that entail the development of multiple cutaneous and mucous membrane vascular lesions associated with other life-threatening complications. This chapter deals with the clinical and pathologic features of three such conditions, namely, Osler-Weber-Rendu (OWR) syndrome, ataxia-telangiectasia (AT), and Fabry’s disease (FD).

What’s New in Dermatopathology?

DNA microarrays were developed in the mid 1990s and are an efficient tool that can take a snapshot of a cells active expressed DNA. By allowing fast and inexpensive analysis, microarrays have exploded in use. They work by fixing a short segment of cDNA or segment of oligonucleotides called a probe, to a silicon or glass backing. The probes are exposed to tissue extracted nucleic acids and if present will bind to the probe causing fluorescence. A single microarray chip the length of a matchstick can fit tens of thousands of probes at relatively low cost providing significant advantage over other techniques.

Staphylococcal Toxin-Mediated Scalded Skin and Toxic Shock Syndromes

Credit for the first clinical description of SS belongs to Ritter von Rittershain, who in 1878 described 297 cases of a generalized exfoliative exanthem in neonates. An association with staphylococcus and subsequently the mechanism of phage-mediated toxin elaboration would be discovered in the 1940s and 1950s. The toxin-mediated staphylococcal syndromes of staphylococcal scalded skin syndrome (SSSS) and toxic shock syndrome (TS) constitute important dermatologic entities capable of producing significant morbidity and mortality. Distinctive clinical and pathologic attributes usually permit their early recognition, allowing for prompt institution of potentially lifesaving therapy.