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Multicentric reticulohistiocytosis is a rare syndrome of adulthood characterized by the rapid appearance of multiple papules and nodules arising in conjunction with a severe, mutilating arthritis. When occurring as part of the syndrome, the reticulohistiocytomas are found on mucosal surfaces in up to 50% of cases (1-2). Visceral reticulohistiocytomas involving lymph nodes, bone marrow, lungs, and endocardium have also been described in patients with the syndrome (3,4). Cardiac involvement may result in cardiac failure in extreme cases. Xanthomatous lesions may also be present. The destructive osteoarthritis tends to be symmetrical and involves primarily the joints in the hands. The knees and wrists are also involved in greater than 50% of cases. The arthritis may precede, occur concurrently with, or follow the appearance of the cutaneous lesions but is the presenting sign in most cases. After a period of rapid deterioration, the arthritis usually stabilizes, but does not improve. In approximately 30% of cases, the constellation of multiple reticulohistiocytomas and destructive osteoarthritis has been associated with visceral malignancies (3,5,6). [ABSTRACT FROM AUTHOR]

Kawasaki disease, or mucocutaneous lymph node syndrome, was first described in Japan in the late 1960s as an illness characterized by persistent fever, conjunctivitis, mucous membrane changes, acral erythema with desquamation, and cervical adenopathy, associated with coronary arteritis (1,2). While earlier descriptions of the disease were limited to Asia and Hawaii, the disease is now known to occur worldwide. The disease is primarily one of young children, with 85% of cases occurring in children under five years. It is uncommon in children less than 6 months. There have been some epidemiologic investigations linking Kawasaki disease to freshly cleaned carpets, humidifier use, and living near a body of water, but these associations have not been observed consistently (3). [ABSTRACT FROM AUTHOR]

Polyarteritis nodosa is a systemic vasculitis that involves predominantly medium-sized vessels. In 1852,Rokitansky described a man who presented with fever, abdominal pain, and bloody diarrhea, and shortly thereafter expired. Autopsy findings included small aneurysms of the arterial system, sparing the arteries of the brain and the large arteries. The aneurysms were identified as inflammatory and the disease was named periarteritis nodosa by Kussmaul and Maier in 1866. The term polyarteritis nodosa was introduced by Ferrari in 1903 to emphasize the transmural inflammation that characterizes this vasculitis (1). Because polyarteritis nodosa has overlapping features with other forms of systemic vasculitis, the nosology has been confusing. Interpretation of data from case series in the literature is difficult because many series are comprised of patients now regarded as having had different diseases. This summary of polyarteritis nodosa will describe the disease in its classic form and briefly discuss the other entities that may have a similar pattern of vasculitis. [ABSTRACT FROM AUTHOR]

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 (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 to 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. [ABSTRACT FROM AUTHOR]

Calciphylaxis is a syndrome of subcutaneous vascular calcification resulting in painful ulcers on the legs, thighs, or abdomen. The disease develops almost exclusively in patients with end-stage renal disease, and is frequently fatal due to infectious complications. Calciphylaxis was described in 1962 by Hans Selye. He made rats hypercalcemic with "sensitizers" vitamin D or parathyroid hormone. "Challengers" were then administered. These included skin injury by hair-plucking, or injections of various sorts. Injured areas calcified and became ulcerated. Injection of "challengers" intravenously resulted in systemic necrotic lesions associated with tissue calcification (1). The concept of calciphylaxis has been imperfectly applied to cutaneous ulcerations that develop in patients with end-stage renal disease due to vascular calcification and subsequent occlusion. While this clinical scenario has some parallels with Selye's experiments, his experimental subjects were not uremic, and the calcifications were not vascular. Therefore, "calciphylaxis" does not accurately describe the syndrome. Because this disease does not conform to the model of calciphylaxis as described by Selye, many advocate eliminating that label in favor of "calcific uremic arteriolopathy." [ABSTRACT FROM AUTHOR]

In 1923, Jaksch-Wartenhorst described a 32-year-old man with polyarthritis and fever who subsequently developed bilateral auricular and nasal chondritis. He applied the term polychondropathia to this entity (1). In 1960, Pearson and colleagues added four more cases, and coined the term relapsing polychondritis, which has become the accepted terminology for this disease (2). [ABSTRACT FROM AUTHOR]

Eruptive xanthoma (EX) is a serious systemic dyslipidemia with distinctive cutaneous features. Although the dermatologic manifestations are not in themselves serious, their presence may be the harbinger of serious visceral disease. EX is an uncommon disease with a near equal gender incidence, principally seen in two age groups with different predisposing factors. Among children and young adults genetic disturbances in lipid metabolism are largely responsible and include lipoprotein lipase deficiency and Type I and V hyperlipoproteinemia (1). In older adults, acute ethanol ingestion and endocrinologic disturbances including hypothyroidism and diabetes mellitus are often observed. Common to these clinical settings is the presence of serum hypertriglyceridemia and/or elevated very low-density lipoproteins (VLDL) (2). Triglycerides are transported in the serum as a composite, known as a chylomicron, consisting of lipid with the apolipoproteins B-48, C-II, C-III, E, A-I, and A-IV. The apolipoproteins are critical in the metabolism of the chylomicrons. Chylomicrons are synthesized in the intestine and circulate in the serum, passing off triglycerides to the peripheral tissue endothelial capillaries via the enzymatic action of lipoprotein lipase and the binding of apolipoprotein C-II. [ABSTRACT FROM AUTHOR]

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 life-saving therapy. [ABSTRACT FROM AUTHOR]

Meningococcemia is an invasive bacterial infection by the gram-negative diplococcus, Neisseria meningitidis, which is often rapidly fatal if not detected and treated early. Neisseria meningitidis infections occur both endemically and epidemically. Sporadic disease occurs more commonly during winter and early spring months, and affects predominantly children. The highest rate of infection is in infants six months to one year, with a steady decline in infection rate with age. This is likely explained by passive maternal immunity providing protection in the first six months, and gradual onset of acquired immunity with age. Approximately two-thirds of invasive meningococcal disease occurs in children (1). The human bacterial reservoir is the upper respiratory tract. In the general population, the carrier state is quite common, but in only rare cases do carriers develop invasive disease. There are many different serotypes of Neisseria meningitidis, but types A, B, C, W-135, and Y account for nearly all invasive disease. Worldwide, type A is responsible for most large epidemics, but in the United States, serotypes B and C account for approximately 90% of invasive infections. [ABSTRACT FROM AUTHOR]

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 syndrome, ataxiatelangiectasia, and Fabry's disease. [ABSTRACT FROM AUTHOR]

Smallpox, otherwise known as variola, was first described in ancient Chinese texts dating from the eleventh century B.C. The Chinese were the first to discover that purposeful inoculation of lesional material into the nose of the un infected was preventative of disease in the sixth century B.C. (1). Although the disease was officially eradicated in 1979, known stocks of the material have been maintained in biolabs located in Russia and the United States, where they pose a potential source of public health concern if subverted as biowarfare agents (2-5). Smallpox belongs to the Poxvirus group of double-stranded DNA containing viruses that includes vaccinia, molluscum contagiosum, and cowpox. The poxviruses are among the largest of all human viruses, attaining a maximum diameter of 300 nm, and possess characteristic rectangular or cylindrical outer capsids and a central DNA core (6). [ABSTRACT FROM AUTHOR]

Anthrax is an infection caused by the spore-forming bacterium, Bacillus anthracis. Infection occurs in mammals, particularly herbivores that ingest bacterial spores from soil. Human infection occurs from inhalation of spores, ingestion of animal meat contaminated with spores, or percutaneous inoculation of spores from exposure to infected animals or contaminated animal products. Anthrax has been an occupational disease of textile workers, farmers, butchers, veterinarians, and shepherds. [ABSTRACT FROM AUTHOR]

Necrolytic migratory erythema (NME), referred to as the glucagonoma syndrome, is a rare paraneoplastic syndrome consisting of the classic triad of diarrhea, diabetes mellitus, and rash associated with serum hyperglucagonemia (1-3). The most common etiology involves the elaboration of glucagons from an islet cell tumor of the pancreas but may rarely follow the metabolic consequences of cirrhosis, pancreatic insufficiency, or celiac disease. There is no ethnic or gender predilection and age of onset is usually in the sixties. NME is associated with type 1 multiple endocrine neoplasia syndrome (MEN I) sequence and/or Zollinger-Ellison hypergastrinemia syndrome in a minority of the cases (4-6). [ABSTRACT FROM AUTHOR]

The rickettsioses constitute a diverse group of arthropodborne human diseases capable of producing significant morbidity and mortality. They share important pathologic and clinical attributes that permit their diagnosis in most instances (1). The rickettsioses are responsible for a great number of deaths seen particularly in times of war. It is estimated that over 3 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. [ABSTRACT FROM AUTHOR]

Ecthyma gangrenosum describes a cutaneous infection with Pseudomonas aeruginosa that is manifested by necrotic plaques with an eschar. The infection usually occurs in immunosuppressed patients. Three to six percent of Pseudomonas septicemia is complicated by ecthyma gangrenosum (1). The term ecthyma gangrenosum was given by Hitschmann and Kreibich in 1897 in Germany to describe necrotic cutaneous plaques due to cutaneous involvement in disseminated Pseudomonas infection. However, ecthyma gangrenosum is now known to be a morphologic pattern of cutaneous infection caused by a wide variety of organisms. [ABSTRACT FROM AUTHOR]

Scleromyxedema is a cutaneous condition that is associated with paraproteinemia in more than 80% of cases (1). In the vast majority of cases, the paraprotein is an IgG heavy chain and a γ light chain. Rare cases of к light chains have been reported, and polyclonal hypergammopathy is also seen in some cases. It has been reported that only 10% of patients with scleromyxedema and associated monoclonal gammopathy will progress to multiple myeloma (1). Overall, scleromyxedema is associated with an increased mortality rate, probably due to the manifold systemic associations. [ABSTRACT FROM AUTHOR]

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 comprised 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. [ABSTRACT FROM AUTHOR]

Gardner syndrome is a variant of familial adenomatous polyposis, an autosomal dominant disease characterized by multiple adenomatous polyps of the colon that inevitably transform into adenocarcinoma, usually by the fifth decade. Some cases are the result of spontaneous mutations. In 1951, Gardner described a familial adenomatous polyposis kindred with extracolonic manifestations, including bone tumors, and soft "cyst-like" surface tumors (1). Interestingly, the cutaneous lesions were not characterized in that report because one family member had expired shortly after having a cutaneous lesion removed, and others in the family were afraid they would meet the same fate if their lesions were removed. [ABSTRACT FROM AUTHOR]

The amyloidoses encompass a broad category of cutaneous and systemic disorders with important pathogenic consequences. These derive from the direct deposition of abnormal proteins or indirectly relate to potentially deadly systemic disorders that produce such deposits. Each of the amyloidoses can be defined by certain histomorphologic and chemical properties that permit their identification and inclusion into disease categories (1). These designations can be loosely grouped into systemic and cutaneous delimited forms. [ABSTRACT FROM AUTHOR]

Serious systemic diseases, including visceral cancer, may be indirectly signaled by the development of distinctive cutaneous eruptions. Important aspects of these eruptions include 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, and paraneoplastic palmar/plantar keratoderma as they relate to underlying malignancy. [ABSTRACT FROM AUTHOR]

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 (1). 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. [ABSTRACT FROM AUTHOR]

Trichilemmomas are benign epidermal neoplasms that may serve as an indicator of underlying malignancy. Trichilemmomas appear, largely on the head and neck, as exophytic, small, hyperkeratotic papules (Figure 15.1). There is no particular gender predilection and they usually arise during the second decade. When occurring as isolated lesions, these tumors are invariably benign and are of no clinical significance. [ABSTRACT FROM AUTHOR]

In 1977, Birt, Hogg, and Dubé described a kindred of 70 individuals, some of whom presented with small skin-colored papules, predominantly of the face. These developed in early adulthood, and were noted to be inherited in a dominant pattern (1). The histomorphology of the papules was described as "abnormal hair follicles with epithelial strands extending out from the infundibulum of the hair follicle into a hyperplastic mantle of specialized fibrous tissue." The authors applied the term fibrofolliculoma to these lesions. Also described in these patients were trichodiscomas and acrochordons. Trichodiscoma is a benign tumor of perifollicular mesenchyme. It is thought to represent a proliferation of the haarscheibe (hair disk), a perifollicular "richly vascularized dermal pad covered with thick epidermis containing Merkel cells and supplied by a thick myelinated nerve the branches of which end at the lower epidermal surface and on the blood vessels of the dermal pad" (2). It is composed of a dermal interfollicular proliferation of spindle cells in a loose connective tissue matrix with varying amounts of mucin. It may have an orientation parallel to the skin surface. [ABSTRACT FROM AUTHOR]

Sebaceous adenomas are benign adnexal tumors that have no malignant potential. They are of no clinical significance in isolation, but may be indicators of internal malignancy when occurring as part of the Muir-Torre syndrome. Sebaceous adenomas grow as exophytic, yellowish papules and nodules. In most cases, these lesions are less than 1 cm in diameter (1). While they may occur at any body site, they are most common on the face. They usually appear in middle age. Ulceration is not a common feature. [ABSTRACT FROM AUTHOR]

Mammary and extramammary Paget's disease represent two clinical conditions with potentially serious consequences for the patient. Mammary Paget's disease is associated with underlying carcinoma of the breast in virtually all cases. Exact incidence numbers vary, but with meticulous serial sections of major ducts entering into the nipple, foci of ductular carcinoma are identified in most cases (1). The disease has the same epidemiologic characteristics as breast carcinoma, independent of the presence of Paget's disease. It is most frequently encountered in middle-aged to elderly women and it may be unilateral or bilateral. Mammary Paget's disease presents as an erythematous, scaling patch on the nipple (Figure 9.1). [ABSTRACT FROM AUTHOR]

Subcutaneous panniculitis-like lymphoma (SPL) occurs primarily in younger adults, but can arise in persons of any age The usual presentation is that of an ulcerative and hemorrhagic panniculitis, presenting as multiple erythematous nodules often involving the lower extremities and abdomen (Figure 10.1). Coagulopathies are frequently observed in these patients. In addition, many of these patients display constitutional symptoms such as weight loss, fever, and fatigue. This disease may represent what was previously known as cytophagic histiocytic panniculitis, at least in some cases (1). The prognosis is ominous for some patients with the disease, while others tend to have a more indolent course (2). Fatal leukemic transformation has also been reported in these patients (3). While the parameters that affect the ultimate course of the disease and prognosis have not been fully elucidated, there have been preliminary attempts at developing criteria for those with a more favorable prognosis (4). [ABSTRACT FROM AUTHOR]

Cutaneous metastases occur in approximately 10% of all cancer patients. The frequencies of cutaneous metastases correlate directly with the frequencies of primary malignancies. In women, breast carcinoma is the most common tumor to spread to the skin, followed by large intestine, melanoma, lung, and ovary. In men, primary tumors from the lung most commonly involve the skin, followed by tumors of the large intestine, melanoma, and squamous cell carcinomas of the oral cavity (1). Metastases can affect any part of the body, with a disproportionate number involving the scalp (presumably due to increased circulatory volume). Overall, skin metastases represent the presenting sign of underlying malignancy in about 8% of these patients (2). Umbilical metastases have been given the designation Sister Mary Joseph nodules, named for a nurse involved with the first surgical resection of such a lesion. Umbilical metastases involve from 5% to 10% of tumors involving the abdomen and may be the presenting sign of an internal malignancy in up to 45% of cases. In one study, 57% of tumor nodules located in the umbilicus were benign (3). Neoplasms originating in the gastrointestinal tract account for the great majority of the metastatic processes (Table 8.1) (1). Other primary neoplasms with umbilical metastases have been reported less commonly. These include adenocarcinomas of the gall bladder (4), renal cell carcinoma (5), and lymphoma (6). [ABSTRACT FROM AUTHOR]

Merkel cell carcinoma, as first described by Toker, et al. (1) in 1972, and otherwise known as trabecular carcinoma of the skin, neuroendocrine carcinoma of the skin, cutaneous APUDoma, primary small cell carcinoma of the skin with endocrine differentiation, is an uncommon, aggressive cutaneous neoplasm. Friederich Merkel first discovered the Merkel cell in 1875. It is a large, clear, usually round or oval cell found in the basal layer of the epidermis. It is found in close association with terminal axons, and is joined to keratinocytes. They are found in highest concentrations in acral skin, namely the fingertips and nasal tip, as well as glabrous skin, hairy skin, and mucous membranes. The exact function of Merkel cells is unclear, but it is generally thought that they are a form of touch receptor (2-4). The origin of Merkel cell carcinoma is controversial as well. It may arise from epidermal Merkel cells, dermal neuroendocrine cells, or poorly differentiated epidermal stem cells. [ABSTRACT FROM AUTHOR]

Cutaneous mast cell disease has several different manifestations. It can present during the neonatal period or throughout life. Different age populations generally develop different clinical manifestations and different associated conditions. It is the systemic form of mastocytosis in adults that has the most potentially severe complications. It has been estimated that from 15% to 50% of patients with adult-onset mast cell disease will have systemic involvement (1,2). However, for the sake of completeness, the other variants of this disease spectrum will also be considered. Urticaria pigmentosa is the global term for all conditions that are characterized by increased numbers of mast cells within the dermis. There is no gender predilection. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) refers to a collection of syndromes, characterized by infiltration of various tissues by Langerhans cells. In 1941, Farber suggested that eosinophilic granuloma, Letterer-Siwe disease, and Hand-Schüller-Christian disease all represent different manifestations of a single pathologic process, and in 1953, Lichtenstein used the term "histiocytosis X" to encompass these entities (1,2). Subsequent to the description of Birbeck granules as a specific ultrastructural marker for Langerhans cells (3), the infiltrating cells of histiocytosis X were identified as Langerhans cells. In 1987, the Writing Group of the Histiocyte Society proposed that Langerhans cell histiocytosis replace the term histiocytosis X as more appropriate (4). [ABSTRACT FROM AUTHOR]

Granulomatous slack skin (GSS) is a subtle variant of mycosis fungoides that is easily overlooked on initial biopsy due to its well-formed granulomatous appearance (1). The initial clinical presentation is similar to that of conventional mycosis fungoides in that patients present with erythematous-to-violaceous patches and plaques. As the lesions progress, however, pendulous folds develop on flexural surfaces of extremities, especially the axillae and inguinal regions (Figure 3.1). Less commonly, the skin on the trunk is affected. At this point in the course of the disease, the clinical appearance is similar to that of cutis laxa. This extremely rare variant of mycosis fungoides affects middle-aged adults with a slight predilection for women in some, but not all, series (2-5). It is most common in Caucasians. [ABSTRACT FROM AUTHOR]

Cutaneous B-cell lymphoma is not a single disease, but rather a family of neoplastic processes characterized by a proliferation of malignant B lymphocytes. These lymphomas may arise de novo on the skin (primary cutaneous B cell lymphoma) or spread to the skin as part of a systemic disease (secondary cutaneous B-cell lymphoma). It is not possible to make this distinction based purely on histologic findings, and a systemic work-up is required in all of these patients in order to determine the extent of disease. The prognosis is greatly altered depending upon this extent. As subtypes of lymphoma correlate with clinical correlation, histologic findings, and prognosis, several of the most prevalent subtypes will be described individually. [ABSTRACT FROM AUTHOR]

Angiosarcoma (AS), otherwise known as hemangiosarcoma, lymphangiosarcoma, or malignant hemangioendothelioma, is a malignant tumor derived from endothelium that occurs in a variety of anatomic sites including the skin (1-3). Sixty percent of cases arise within the skin or superficial soft tissues. Although these tumors derive from the vascular endothelium, the exact vascular origin is unknown and likely derives from both the blood vessels and lymphatics. [ABSTRACT FROM AUTHOR]

GVHD is a common consequence of allogeneic bone marrow transplantation. Approximately 3 weeks following complete marrow eradication and the transplantation of allogeneic donor marrow cells, a cutaneous eruption is seen in up to 20% to 80% of patients, and may result in the death of the patient (1,2). The cutaneous manifestations may be the first indication of evolving GVHD. [ABSTRACT FROM AUTHOR]

Pancreatic panniculitis is a form of subcutaneous fat necrosis that occurs as a rare manifestation of various pancreatic diseases, most commonly pancreatitis, or pancreatic carcinoma. Fat necrosis at remote sites occurs in only a small percentage of those with pancreatic disease. Its pathogenesis is uncertain. A review of 893 hospital admissions for various pancreatic diseases revealed only three cases of pancreatic panniculitis (1). Circulating pancreatic enzymes, lipase and amylase, are elevated in most but not all cases of pancreatic panniculitis (2). Human pancreatic lipase has been identified in lesions of pancreatic panniculitis, supporting its role in the pathogenesis of the disease (3). In vitro and clinical observations suggest that factors other than circulating amylase and lipase are necessary for the development of pancreatic panniculitis. In vitro incubation of human adipose tissue with pancreatic enzymes and serum from a patient with pancreatic panniculitis and elevated enzymes failed to induce fat necrosis, suggesting that there are other local factors or a labile circulating factor needed to induce the necrosis (4). [ABSTRACT FROM AUTHOR]

Cutaneous leiomyomas are uncommon tumors that arise from arrector pili muscle (pilar leiomyoma), genital smooth muscle (genital leiomyoma), or vascular smooth muscle (angioleiomyoma). Angioleiomyomas are histologically distinct, and are not known to occur as multiple lesions. Most pilar leiomyomas occur singly, but can occur as multiple lesions. As multiple lesions, they may occur in association with uterine leiomyomas and, rarely, leiomyosarcomas, in the multiple cutaneous and uterine leiomyomatosis (MCUL) syndrome. More recently, cutaneous and uterine leiomyomas have been reported to occur in association with renal cell carcinoma in the hereditary leiomyomatosis renal cell cancer (HLRCC) syndrome (1). MCUL and HLRCC likely represent part of a spectrum of one disease. These syndromes are both familial and transmitted in an autosomal dominant pattern, with variable penetrance. The implicated gene encodes fumarate hydratase, an enzyme in the Krebs cycle that maps to chromosome 1q42.3-q43 (2). Fumarate hydratase (FH) is distributed predominantly within mitochondria, but also within the cytosol, of mammalian cells. [ABSTRACT FROM AUTHOR]

Leukemia cutis is an uncommon cutaneous eruption that may be difficult to diagnose. In the vast majority of patients, there is a known history of leukemia at the time of the skin manifestations. However, leukemia may have its initial manifestation in the skin, in some cases with simultaneous bone marrow involvement, or less commonly, in the absence of simultaneous marrow involvement. (In these cases, the cutaneous eruptions have been called extramedullary myeloid tumors (1)). In one series, approximately 38% of patients had cutaneous findings at the time of bone marrow diagnosis (2). In other series, anywhere from 3% to 7% of patients had cutaneous lesions prior to detection of marrow involvement (3). Patients with all types of leukemia may demonstrate cutaneous lesions. It has been reported in 2% to 3% of patients with acute myelogenous leukemia (4). Cutaneous involvement is less common in patients with acute lymphoblastic leukemia (5). Chronic myelogenous leukemia patients have skin manifestations in 6% to 20% of cases (6). The incidence ranges from 4% to 20% in patients with chronic lymphocytic leukemia (7). [ABSTRACT FROM AUTHOR]