https://cdr.lib.unc.edu/downloads/02870x81q

Genomic Classification of Cutaneous Melanoma

Juvenile xanthogranulomas (JXG) is a histiocytic disorder, primarily but not exclusively seen throughout the first two decades of life and principally as a solitary cutaneous lesion. This study is a retrospective clinical and pathologic review of 174 cases documenting the cutaneous and extracutaneous manifestations in patients presenting from the neonatal period to 20 years of age (mean 3.3 years; median 1 year). There was a male predominance (99 male:75 female) in all categories of clinical presentation, but especially notable in the group with multiple cutaneous lesions (12 male:1 female). A solitary cutaneous lesion accounted for 67% of all cases, followed by a solitary subcutaneous or deep soft tissue mass (28 cases, 16%), multiple cutaneous lesions (13 cases, 7%), a solitary extracutaneous, nonsoft tissue lesion (9 cases, 5%), and multiple cutaneous and visceral-systemic lesions (8 cases, 5%). The recorded deaths due to disease included two neonates with systemic JXG who developed hepatic failure and thrombocytopenia and at autopsy had giant cell-neonatal hepatitis in addition to JXG in the liver and other visceral sites. A third death in a 3-month-old boy with a retroperitoneal-pelvic JXG occurred after failure to control severe hypercalcemia. The characteristic Touton giant cell in variable numbers was a consistent feature of the cutaneous lesions; however, these cells were either absent or present in reduced numbers in the various extracutaneous lesions when compared with JXG in the skin. Spindle cells intermingled among the mononuclear cells or forming short fascicles were seen in both cutaneous and extracutaneous lesions. Immunohistochemistry was performed on all extracutaneous lesions, and the constituent cells, regardless of their individual morphologic features, were uniformly positive for vimentin, CD68, and factor XIIIa and negative for S-100 protein and CD1a. It is widely held that JXG is a proliferative disorder of dendrocytes, possibly dermal dendrocytes; thus, its clinical and pathologic similarities to Langerhans cell histiocytosis are not entirely unexpected in light of the most recently proposed international classification of histiocytic disorders, which includes JXG and Langerhans cell histiocytosis together as "dendritic cell-related" histiocytoses.

Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations.

Juvenile xanthogranulomas (JXG) is a histiocytic disorder, primarily but not exclusively seen throughout the first two decades of life and principally as a solitary cutaneous lesion. This study is a retrospective clinical and pathologic review of 174 cases documenting the cutaneous and extracutaneous manifestations in patients presenting from the neonatal period to 20 years of age (mean 3.3 years; median 1 year). There was a male predominance (99 male:75 female) in all categories of clinical presentation, but especially notable in the group with multiple cutaneous lesions (12 male:1 female). A solitary cutaneous lesion accounted for 67% of all cases, followed by a solitary subcutaneous or deep soft tissue mass (28 cases, 16%), multiple cutaneous lesions (13 cases, 7%), a solitary extracutaneous, nonsoft tissue lesion (9 cases, 5%), and multiple cutaneous and visceral–systemic lesions (8 cases, 5%). The recorded deaths due to disease included two neonates with systemic JXG who developed hepatic failure and thrombocytopenia and at autopsy had giant cell-neonatal hepatitis in addition to JXG in the liver and other visceral sites. A third death in a 3-month-old boy with a retroperitoneal–pelvic JXG occurred after failure to control severe hypercalcemia. The characteristic Touton giant cell in variable numbers was a consistent feature of the cutaneous lesions; however, these cells were either absent or present in reduced numbers in the various extracutaneous lesions when compared with JXG in the skin. Spindle cells intermingled among the mononuclear cells or forming short fascicles were seen in both cutaneous and extracutaneous lesions. Immunohistochemistry was performed on all extracutaneous lesions, and the constituent cells, regardless of their individual morphologic features, were uniformly positive for vimentin, CD68, and factor XIIIa and negative for S-100 protein and CD1a. It is widely held that JXG is a proliferative disorder of dendrocytes, possibly dermal dendrocytes; thus, its clinical and pathologic similarities to Langerhans cell histiocytosis are not entirely unexpected in light of the most recently proposed international classification of histiocytic disorders, which includes JXG and

Juvenile Xanthogranulomas in the First Two Decades of Life

BACKGROUD:

Sebaceous carcinoma is a rare and aggressive cutaneous carcinoma. It is believed that this malignancy predominates in the periocular region and occurs more frequently in Asian populations and in women. The objective of the current study was to analyze demographic characteristics and outcomes for patients with this malignancy from a large United States-based population registry.



METHODS:

An analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Results database from 1973 through 2004 was performed.



RESULTS:

Of 1349 patients who were identified, 54% were men, 86.2% were white, and 5.5% were of Asian/Pacific Islander ancestry. The median age at diagnosis was 73 years. The most frequent site of disease was the eyelid (38.7%). The population-matched 5- and 10-year age-matched relative survival rate was 91.9% (standard error [SE], 1.9%) and 79.2% (SE, 3.7%), respectively. Cause of death was attributable to cancer in 31% of patients. Orbital involvement did not predict for worsened survival compared with nonorbital involvement (5-year overall survival, 75.2% vs 68%, respectively; P = .66). The overall population-matched rate of sebaceous carcinoma was highest in whites (2.03 cases per 1000,000; SE, 0.08) versus Asian/Pacific Islanders (1.07 per 1000,000; SE, 0.18; P = .0001) versus blacks (0.48 per 1000,000; SE, 0.11; P < .0001).



CONCLUSIONS:

The current results support the finding of a predominance of men among patients with sebaceous carcinoma, and no difference was observed in the prognosis for orbital and periorbital involvement. This retrospective analysis also corroborated previous case reports of a higher incidence among patients with advanced age and the highest incidence for sites in the eyelid and skin of the face. The results also established that Asian/Pacific Islander ancestry is not a risk factor for developing sebaceous carcinoma. Cancer 2009. © 2008 American Cancer Society.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.23952

A retrospective review of 1349 cases of sebaceous carcinoma

Based on our series of 111 cases of non-Langerhans cell histiocytoses, we present a new unifying concept for this rare group of disorders. The common denominator is the monocyte/ macrophage, which presents with various histologic features probably due to the influence of cytokines. Non-Langerhans cell histiocytoses are classified according to the predominant mononuclear (vacuolated, spindle-shaped, xanthomatized, scalloped, and oncocytic) and/or multinucleate (Touton, ground-glass appearance, Langhans, and foreign body) histiocytic cell types. Variable mixtures of these cell types produce common polymorphous patterns with prominence of vacuolated, spindle-shaped, and xanthomatized histiocytes in juvenile xanthogranulomas and of scalloped and oncocytic histiocytes in adult xanthogranulomas. Rarely, unusual monomorphous reaction patterns are observed: mostly vacuolated histiocytes are seen in the mononuclear variant of xanthogranulomas, (early benign cephalic histiocytosis, and generalized eruptive histiocytoma. Xanthomatized histiocytes predominate papular xanthoma and rarely xanthoma disseminatum, whereas spindle-shaped histiocytes are evident in spindle cell xanthogranuloma and progressive nodular histiocytosis, scalloped histiocytes are evident in most cases of xanthoma disseminatum, and finally oncocytic histiocytes are evident in reticulohistiocytoma and multicentric histiocytosis. Immunohistochemical, ultrastructural, and clinical findings can rationally be adjusted to this unifying concept of non-Langerhans cell histiocytoses. The time course of lesions, the age of the patients, and the presence or absence of underlying internal diseases are, or may, at least partially, be related to and thus explain variations on the theme of the non-Langerhans cell histiocytic reaction.

Non-Langerhans cell histiocytoses. A new unifying concept.

This report describes 20 sclerosing adnexal carcinomas of the skin that recapitulate the sweat duct and share certain microscopic features with benign syringoma. Clinically, the neoplasms were slow-growing, indurated nodules or plaques. Sixteen were located on the face, including five on the upper lip. Three were situated in the axilla, and one involved the buttock. Twelve of the tumors (group 1) were composed primarily of cords and nests of whorled squamous cells with clear cell change and variable keratinization. Lumens consistent with ductal differentiation were few and isolated in some of these lesions, but others had more numerous and complex ducts. The remaining eight neoplasms (group 2) contained large numbers of small, uniform ducts, and exhibited little keratinization. Each neoplasm in the series infiltrated subcutaneous tissue or deeper tissues and was accompanied by sclerotic, fibrous stroma. Sixteen of the lesions (80%) exhibited perineural growth. One tumor involved an underlying lymph node, probably by direct extension. Cytologic atypicality was mild or lacking, and mitotic figures were sparse. Seven of 15 tumors (47%) with follow-up recurred, in some instances many years after primary excision. Tumor-free margins in the initial excision specimen appeared to be a favorable prognostic factor. The most aggressive lesion in the series showed increased cytologic atypicality in recurrences.

Sclerosing sweat duct (syringomatous) carcinoma

Neoplasms with sebaceous differentiation cover a broad spectrum. They range from benign sebaceous hyperplasia and adenomas to locally infiltrative sebaceous epitheliomas which have biologic behaviors similar to basal cell carcinomas, to sebaceous carcinomas which can have very malignant biologic behaviors. In this paper, we have purposely excluded the nevus sebaceus of .Jadassohn, a nevoid tumor composed of several cutaneous elements. As sebaceous glands are only one part of this tumor, it is better classified as an organoid nevus.

Sebaceous gland neoplasia

We report 6 cases of an unusual variant of cutaneous fibrous histiocytoma in which nuclear palisading is a prominent feature. The lesions were equally distributed between males and females with a widely variable age range. Half of the cases occurred on the digits. Histopathologically, the lesions were characterized by areas of nuclear palisading with formation of Verocay-like bodies in addition to the more typical features of the "fibrous" variant of cutaneous fibrous histiocytoma. The differential diagnostic features between these lesions and those of other tumors in which nuclear palisading is seen are discussed.

Palisading cutaneous fibrous histiocytoma.

Juvenile xanthogranuloma occurring in soft tissue is rare and has received little attention. This report describes cases of deep juvenile xanthogranuloma occurring in the soft tissues of three children. Each tumor was a solitary lesion that arose, respectively, in the superficial skeletal muscles of an 8-month-old girl, the subcutis of the scalp of a 3-month-old boy, and the subcutis of the forehead of a 10-year-old girl. Two lesions were grossly firm, tan-yellow, and homogeneous. Histologically, the subcutaneous lesions were relatively circumscribed; the third lesion infiltrated muscle and contained widely separated skeletal muscle fibers. All lesions showed sheets of uniform amphophilic or acidophilic cells with occasional eosinophils and rare Touton giant cells. In two cases and in cutaneous controls, positive immunoperoxidase stains (HAM-56, HHF-35, and vimentin) supported macrophagic-myofibroblastic differentiation. S-100 protein, MAC-387, and factor XIIIa were negative. Electron microscopy in one case also supported macrophagic-myofibroblastic differentiation. Langerhans granules were absent. Follow-up of 7, 6, and 5 years indicated no recurrences. The differential diagnosis includes deep fibrous histiocytoma and cellular subcutaneous neural tumors.

Deep Juvenile Xanthogranuloma: Subcutaneous and Intramuscular Forms

Synovial metaplasia has been described in bone or soft tissues following surgical procedures or under experimental conditions. Three cases in which skin biopsies showed synovial metaplasia of the dermis are herein reported. The metaplastic foci were associated with cyst formation and transepidermal fistulae. All patients had a history of previous surgical procedures in the area, and in all, the lesions clinically resembled suture granulomas. Microscopically, the lesions bore a striking resemblance to hyperplastic synovium. The immunohistochemical studies showed strong staining with vimentin and scattered positivity with alpha-1-antichymotrypsin (alpha-1ACT) and lysozyme. No basement membrane antigens or elastic fibers were demonstrated. We believe that the name "metaplastic synovial cyst" is an appropriate pathologic designation for this entity. An increased awareness of its occurrence will help to establish its true incidence.

D. J. Santa Cruz

Papers

Sclerosing sweat duct (syringomatous) carcinoma

Sebaceous gland neoplasia

Palisading cutaneous fibrous histiocytoma.

Deep Juvenile Xanthogranuloma: Subcutaneous and Intramuscular Forms

Synovial metaplasia of the skin.