Unilateral Periocular Intralymphatic Histiocytosis, Associated With Rosacea (Morbihan Disease).

Intralymphatic histiocytosis is a rare reactive skin condition characterized by a nonspecific clinical presentation and, microscopically, by the collections of mononuclear histiocytes within the lumina of dilated lymphatic vessels. We report a rare case of intralymphatic histiocytosis associated with rosacea and prominent periocular edema (Morbihan disease). The patient is a 56-year-old woman with a 12-year history of rosacea who suddenly developed edema of the right upper eyelid that persisted 6 months before she sought medical advice. Because of an unclear clinical diagnosis, surgical excision of the edematous upper eyelid was performed. The histologic slides showed interstitial edema of the dermis with dilated vascular channels and small epithelioid cell granulomas around hair follicles. In addition, there were aggregates of cells inside numerous lymphatic vessels that were immunohistochemically positive for CD45, CD4, CD68, CD163, CD64, CD14, CD11c, and lysozyme and negative for CD3, CD20, CD30, CD56, S100, CD1a, and langerin.

Kaposi Sarcoma in Association With an Extracavitary Primary Effusion Lymphoma Showing Unusual Intravascular Involvement: Report of a Case Harboring a FAM175A Germline Mutation.

Primary effusion lymphoma (PEL) is a rare form of aggressive B-cell lymphoma characterized by a malignant serous effusion involving body cavities. It usually associated with human herpes virus-8 (HHV-8) and coexpression of Epstein-Barr virus and mostly affects patients with HIV. We report a rare case of cutaneous PEL with an unusual intravascular presentation, combined with Kaposi sarcoma involving the skin, lung, and gastrointestinal tract. The molecular genetic analysis of the sarcoma and lymphoma components, using next-generation sequencing was performed. The patient was a 67-year-old man who presented with multiple cutaneous tumors and mass in the left lung. He died 17 hours after the admission to the hospital. At autopsy, in addition to the cutaneous lesions, tumors in the left lung and gastrointestinal mucosa were detected, and no effusions in the body cavities were seen. The biopsy from the cutaneous lesions, pulmonary, and intestinal tumors revealed histological and immunohistochemical features of Kaposi sarcoma. In addition, the skin biopsy specimens contained a diffuse infiltrate composed of large pleomorphic cells, with focal intravascular growth that were negative for pan B-cell markers, weakly positive for CD38 and CD138 but expressed CD3, HHV-8, and Epstein-Barr virus. Molecular genetic studies in this specimen revealed monoclonal rearrangements of the IgH gene. The diagnosis of PEL, solid variant, was made. Next-generation sequencing analysis of the tumorous and normal tissue detected a pathogenic germline mutation of the FAM175A gene and somatic mutations in BRCA2 and RAD51B (in both sarcoma and lymphoma specimens), and INPP4B and RICTOR (in lymphoma specimen only).

Mummified Cells are a Common Finding in Cutaneous Hodgkin Lymphoma and Can Be Used as a Diagnostic Clue.

Specific cutaneous involvement in Hodgkin lymphoma is rare. In cutaneous lesions, the diagnosis is usually based on the recognition of diagnostic Reed-Sternberg cells and its variants. In nodal Hodgkin lymphoma, so-called mummified cells (cells with condensed cytoplasm and pyknotic eosinophilic or basophilic nuclei) are often seen. They are sometimes conspicuous and easy to recognize, thus serving as a clue to the diagnosis. Our objective was to study cases of cutaneous Hodgkin lymphoma to identify the occurrence of mummified cells. We studied 12 patients (4 women and 8 men; age range 23-80 years). In 6 patients, cutaneous and extracutaneous disease was identified almost simultaneously; in 4 patients, lymph node disease preceded cutaneous involvement; and in the remaining 2 patients, the skin lesions were the presenting sign, whereas lymph node involvement occurred later. Histopathological, immunohistochemical, and molecular-genetic studies, including rearrangements for TCR, IgH genes, and PCR for EBV, were performed. Cutaneous biopsy specimens revealed either a multinodular or diffuse infiltrate, included small lymphocytes, eosinophils, plasma cells, and macrophages, but in all cases, diagnostic Reed-Sternberg cells and its variants were identified. Mummified cells were detected in 9 cases, either as occasional scattered mummified cells often requiring a search (6 cases) or being conspicuous, grouped and therefore easily identified (3 cases). Immunohistochemically, in all 7 cases studied, mummified cells were positive for both CD30 and CD15. It is concluded that mummified cells are encountered in a majority of cases of cutaneous Hodgkin lymphoma.

A Case of Lymphomatoid Papulosis Type E With an Unusual Exacerbated Clinical Course.

Lymphomatoid papulosis (LyP) type E is a recently delineated variant characterized by the occurrence of large necrotic "eschar"-like lesions displaying microscopically angioinvasive and angiodestructive infiltrates composed of CD30 lymphocytes, frequently coexpressing CD8. In contrast to other LyP variants where patients develop multiple lesions, most patients with LyP type E present with few lesions (often 1 or 2 at a given time). In this article, we describe a 34-year-old man with LyP type E with an exacerbated clinical course characterized by the occurrence of almost a hundred of lesions. Initially, he presented with a single rapidly growing 2-cm large erythematous nodule on the forearm but after the administration of doxycycline multiple eschar-like lesions developed all over the body. Atypical lymphoid infiltrates with marked angiocentricity and angiotropism of CD30 medium-sized to large pleomorphic lymphocytes were seen histopathologically. After the withdrawal of the antibiotic, the lesions spontaneously regressed. Awareness of this rare LyP variant and its correct recognition, even if the clinical course is unusual and worrisome, is important to avoid aggressive treatment.

Mycosis Fungoides Manifesting as Giant Cell Lichenoid Dermatitis.

Mycosis fungoides (MF) is the most common form of primary cutaneous lymphoma with a broad clinicopathological spectrum. Unusual histopathologic patterns of MF include lichenoid, interstitial, folliculotropic, spongiotic, granulomatous, and many others. Several cases of unusual lichenoid reaction characterized by a mixed lichenoid inflammatory infiltrate with prominent infiltration of the papillary dermis and epidermis by multinucleated giant cells were described under the name of "giant cell lichenoid dermatitis," most of them were considered to represent a drug eruption. Herein, we describe a 77-year-old woman with a 5-year history of MF displaying microscopic features of giant cell lichenoid dermatitis. Histology revealed a dense band-like lichenoid epidermotropic infiltrate composed of CD4 small to medium-sized lymphocytes with cerebriform nuclei with the presence of multinucleated giant cells in the papillary dermis, within the epidermis, and some hair follicles. Monoclonal TCR gene rearrangement was detected using PCR. To the best of our knowledge, this pattern was never described in MF.

Small Subset of Adenoid Cystic Carcinoma of the Skin Is Associated With Alterations of the MYBL1 Gene Similar to Their Extracutaneous Counterparts.

Adenoid cystic carcinoma (ACC) of the skin is a rare malignant neoplasm histologically identical to homonymous tumors in other organs. Cutaneous ACC has been found to harbor MYB gene activations, either through MYB chromosomal abnormalities or by generation of the MYB-NFIB fusion. In salivary gland ACC, in addition to the MYB gene, alterations in MYBL1, the gene closely related to MYB, have been reported. We studied 10 cases of cutaneous ACC (6 women, 4 men; and age range 51-83 years) for alterations in the MYB, NFIB, and MYBL1 genes, using FISH and PCR. MYB break-apart and NFIB break-apart tests were positive in 4 and 5 cases, respectively. MYB-NFIB fusions were found in 4 cases. The break of MYBL1 was found in 2 cases, and in one of them, the NFIB break-apart probe was positive, strongly indicating a MYBL1-NFIB fusion. In 2 cases, the MYB break-apart test was positive, whereas no MYB-NFIB was detected, strongly suggesting another fusion partner. It is concluded that MYBL1 alterations are detected in primary cutaneous ACC but are apparently less common compared with MYB and NFIB alterations.

A Rare Case of Solitary Hemorrhagic Mycosis Fungoides With Angiocentric Features.

Unilesional (solitary) mycosis fungoides (MF) is a rare variant characterized clinically by the presence of a single contiguous area of skin involvement covering less than 5% of the body surface and histopathologically by features identical to those seen in classical MF. Angiocentricity (angiodestruction) is mostly a feature of primary or secondary cutaneous lymphomas with an aggressive course and poor outcome, with only very few reports of MF with angiocentric pattern. The authors report an unusual case of solitary patch-stage MF with hemorrhagic features, characterized histologically by epidermotropic and angiocentric (angiodestructive) infiltrate and a reactive B-cell component appearing as lymphoid follicles.

An Immunohistochemical Study of Anogenital Mammary-Like Glands.

Although the normal histology of anogenital mammary-like glands (AGMLG) has been studied, no systemic investigation has been performed on the immunoprofile of these structures. We studied intact AGMLG with a broad panel of antibodies. The immunoprofile of AGMLG is similar to that of a normal breast tissue, and there are similarities to eccrine glands and coils about cytokeratin expression. Our immunohistochemical data may contribute to understanding of the pathogenesis of lesions arising from AGMLG.

Anogenital Mammary-Like Glands: A Study of Their Normal Histology With Emphasis on Glandular Depth, Presence of Columnar Epithelial Cells, and Distribution of Elastic Fibers.

The normal histology of anogenital mammary-like glands (AGMLG) has been studied previously, but some aspects, including glandular depth, presence of columnar epithelium resembling columnar cell change/hyperplasia as defined in mammary pathology, and distribution of elastic fibers, have not been previously investigated. To address these issues, we studied 148 AGMLG identified in 133 paraffin blocks sampled from 64 vulvar wide excision or vulvectomy specimens (64 patients, various indications for surgery). The depth of AGMLG ranged from 0.64 to 3.9 mm. Epithelial columnar cell change was noted in 33.1% of all AGMLG, whereas columnar cell hyperplasia was detected in 10.1%. Occasionally, combinations of cuboidal epithelium and columnar cell change were seen within 1 histological section. Of 22 specimens stained for elastic fibers, in only 6 (27.3%) cases were elastic fibers found around glands. Periductal elastic fibers were demonstrated around 3 of the only 5 ducts, which were available for analysis in slides stained for elastic fibers. The depth of AGMLG should be taken into account when planning topical and surgical therapies for lesions derived or evolving from AGMLG. Alterations identical to columnar cell change may represent a normal variation of AGMLG.

Unusual clinicopathological presentation of primary cutaneous diffuse large B-cell lymphoma, leg type, with multiple nodules and widespread garland-like lesions.

We present a case of primary cutaneous diffuse large B-cell lymphoma, leg type, with an unusual clinical picture. A 41-year-old man presented with a 2-year history of slowly progressive plaques, nodules, and garland-like patches on his chest, right upper arm, and back. Complete staging investigations revealed no extracutaneous involvement. Histological examination of a nodule revealed a diffuse nonepidermotropic infiltrate mainly composed of large blast cells with features of immunoblasts and centroblasts and spindle cells seen at the periphery of the infiltrate. Histological examination of a garland-like lesion showed perivascular infiltrates composed predominantly of small lymphocytes admixed with only occasional large blasts. The blasts from the nodule and garland-like lesions and spindle cells identified in the nodule exhibited an identical phenotype: they stained positively for CD20, CD79a, and bcl-2 and tested negative for bcl-6, CD5, CD10, and TdT. CD35 revealed no networks of follicular dendritic cells. Widespread garland-like lesions are not a typical feature of primary cutaneous diffuse large B-cell lymphoma.

A patient with clinicopathologic features of small plaque parapsoriasis presenting later with plaque-stage mycosis fungoides: report of a case and comparative retrospective study of 27 cases of "nonprogressive" small plaque parapsoriasis.

BACKGROUND: It is unsettled whether small plaque parapsoriasis (SPP) represents an inflammatory dermatosis or has a potential to transform into mycosis fungoides (MF) or is, in fact, MF. The literature contains no fully documented example of progression of SPP into MF. OBJECTIVE: The purpose of our study was to present a patient with clinical features of SPP who later developed plaque-stage MF, as seen both clinically and pathologically and to compare the clinicopathologic features of this unique case with 27 "nonprogressive" SPP cases. METHODS: This study is a prospective and retrospective evaluation of 28 patients, using light microscopy, immunohistochemistry, and molecular biology. RESULTS: A 56-year-old man with a 3-year history of persistent SPP with typical small (<5 cm), elongated and "digitate" lesions presented with newly developed larger patches and plaques. Whereas histologic examination of the patch lesion revealed relatively nonspecific features, a specimen of the crusted plaque showed a dense lymphoid infiltrate composed of small cerebriform lymphocytes, medium-sized lymphoid cells, and occasional large hyperchromatic cells that infiltrated the basal layer of the epidermis and formed small collections. There were atypical mitotic figures. Immunohistochemically, an aberrant immunophenotype with the loss of CD5 expression was found in the plaque specimen. T-cell receptor (TCR)-gamma gene rearrangement studies detected clones in the plaque and in the peripheral blood (biallelic in blood), while the patch tested polyclonal. The 27 SPP patients included 23 men and 4 women, ranging in age from 29 to 75 years. They were followed up and treated for 1.2 to 52 years (mean 10); no patient's SPP progressed into MF. All patients presented with small patch lesions measuring 3 to 6 cm lengthwise and 0.5 to 2 cm in width. Histologic features were nonspecific. Molecular genetic studies revealed the following results: two cases tested polyclonal, 3 cases demonstrated the oligoclonal pattern, whereas the remaining 13 specimens showed a pattern which can be interpreted as oligoclonal or pseudomonoclonal. LIMITATIONS: Oligoclonal and monoclonal patterns were overrepresented in the SPP group, which may be due to the low amount and, probably, suboptimal quality of DNA used in the TCR-gamma rearrangement studies. CONCLUSIONS: Occasionally patients with the clinical and pathologic presentation of SPP may develop typical features for MF. This event seems to be extremely rare; at present there appears to be no means to predict such a course. The vast majority of SPP patients will never have disease progression to MF.

Apocrine mixed tumors of the skin with architectural and/or cytologic atypia: a retrospective clinicopathologic study of 18 cases.

We present a series of 18 atypical apocrine mixed tumors of the skin characterized by architectural and/or cytologic atypia but which nevertheless do not qualify these lesions as carcinomas. There were 15 males and 3 females, and all but 1 presented with solitary nodules ranging in size from 4 to 20 mm; 1 female had a large tumor of 12 cm. The tumors were preferentially located on the head area, especially the face (13 cases). Other locations included the lower extremities (3) and inguinal area (2). In all patients, surgical excision of the tumors was performed. Clinical follow-up was available in 11 cases and ranged from 1 to 24 years (mean 9.6 y; median 5 y). No recurrences or metastases were documented. Overall, the lesions manifested a rather benign architecture, usually with good circumscription, lack of capsular breach or hypercellularity; however, some asymmetry, focally irregular infiltrationlike or pushing tumorous borders were seen. Microscopically, 17 cases conformed to the so-called hyaline cell-rich variant and showed multinucleated, bizarre, hyperchromatic cells in hyaline cell areas that had a myoepithelial immunophenotype; in 1 case, atypical mitotic figures were noted. One case showed mild nuclear pleomorphism in the ductal component. Tumors were negative for p53, including bizarre giant cells that did not label with Ki-67. Ultrastructurally, hyaline cells exhibited features consistent with myoepithelial differentiation. Seven cases studied by immunohistochemistry proved negative for HER-2/neu (c-erbB-2) protein expression, and the HER-2/neu gene was not amplified by fluorescence in situ hybridization analysis in 5 cases tested. As controls, 4 authentic malignant mixed tumors were studied, but these likewise tested negative for HER-2/neu protein expression and showed no gene amplification; 1 malignant mixed tumor had polysomy 17. We conclude that some atypical cytoarchitectural features in apocrine mixed tumors, albeit worrisome, do not indicate a malignant change.

Apocrine mixed tumor of the skin ("mixed tumor of the folliculosebaceous-apocrine complex"). Spectrum of differentiations and metaplastic changes in the epithelial, myoepithelial, and stromal components based on a histopathologic study of 244 cases.

BACKGROUND: A systematic analysis of the entire spectrum of various forms of differentiation and metaplastic epiphenomena in cutaneous apocrine mixed tumor (AMT) has never been performed. OBJECTIVE: The purpose of our study was to study a large number of cutaneous mixed tumors so as to fully characterize the entire spectrum of differentiations and metaplastic changes that may occur in the epithelial, myoepithelial, and stromal components of AMT. METHODS: This article reports a light-microscopic study of 244 cases of cutaneous AMT, complemented by a literature review. RESULTS: All types of differentiation along the lines of the folliculosebaceous-apocrine unit can be seen in AMT. The spectrum of metaplastic changes in the epithelial components includes squamous metaplasia, mucinous metaplasia, oxyphilic metaplasia, clear cell change, columnar metaplasia, hobnail metaplasia, and cytoplasmic vacuolization. The following changes in the myoepithelial component were documented: clear cell change, hyaline cells, plasmacytoid cells, spindling, and collagenous spherulosis. Stromal alterations included chondroid metaplasia, osseous metaplasia, and adipose metaplasia. LIMITATIONS: This study utilizes tissue specimens that mainly came as consultations; therefore some inherent selection bias exists. CONCLUSIONS: AMT displays a wide range of differentiation and metaplastic changes in its epithelial, myoepithelial, and stromal components. These phenomena are not mutually exclusive. When unduly prominent, they may present diagnostic pitfalls. Our findings corroborate those of previous publications, stressing the remarkable diversity of differentiation and metaplasias that may be found in cutaneous AMT. We propose that the most appropriate name for these lesions is "mixed tumor of the folliculosebaceous-apocrine complex."

The role of intradermal proliferation of T-cells in the pathogenesis of psoriasis.

BACKGROUND:: Psoriasis is a common immune-mediated chronic inflammatory disease of the skin and joints, affecting 1-3% of the population. It is generally accepted that the pathogenesis of psoriasis involves accumulation of effector T-cells within lymph nodes and their subsequent migration into the skin through the blood system. Here we provide evidence that psoriatic plaque itself may serve as a source of inflammatory T-cells. OBJECTIVE:: We examined the intradermal proliferation of T-cells and the number of effector/memory (CD45RO+) T-cells in the skin of psoriatic patients at different periods of the disease. METHODS:: Skin samples were obtained from 41 patients with progressive psoriatic lesions; 18 of these patients also donated skin specimens during the remission of the disease. The control group consisted of 16 healthy subjects. Ki-67 immunohistochemical staining was applied to detect proliferating cells, CD3ε served as a T-cell marker, and CD45RA and CD45RO antibodies were utilized to discriminate between naive and effector/memory T-cells, respectively. RESULTS:: Progressive psoriatic lesions demonstrated Ki67 staining both in keratinocytes and in the CD3ε+ cells of dermal infiltrate. Median count of CD45RO+ cells per microscopic field was 15 in healthy controls, 59 in patients in remission and 208 in progressive psoriatic plaques. The observed differences demonstrated high level of statistical significance. STUDY LIMITATIONS:: Limited number of analyzed patients. CONCLUSION:: Progressive phase of psoriasis is characterized by intradermal proliferation of T-cells. Spots of regressed psoriatic lesions contain high number of CD45RO+ cells, which are likely to render an immunological memory.

Spectrum of Changes in Anogenital Mammary-like Glands in Primary Extramammary (Anogenital) Paget Disease and Their Possible Role in the Pathogenesis of the Disease.

To determine whether a subset of primary extramammary Paget disease (EMPD) may originate in anogenital mammary-like glands (AGMLG), the authors studied 181 specimens of EMPD, detailing alterations in AGMLG. The latter were identified in 33 specimens from 31 patients. All patients were women, ranging in age from 38 to 93 years (median, 65 y). In all cases, lesions involved the vulva and in 1 patient the perianal skin was affected. Histopathologically, AGMLG manifested changes identical to columnar cell change (CCC) (87.1%), usual ductal hyperplasia (22.6%), columnar cell hyperplasia (CCH) (9.7%), oxyphilic (apocrine) metaplasia (6.5%), and atypical duct hyperplasia (3.2%). Four cases (12.9%), in addition to intraepidermal carcinoma, harbored invasive carcinoma. In all 4 of these, AGMLG displayed a range of alterations including ductal carcinoma in situ, CCC, and CCH. Three further cases (9.7%) showed ductal carcinoma in situ without any definite invasive carcinoma. Colonization of AGMLG by neoplastic Paget cells was noted in 6 cases. As CCC and CCH may be encountered in normal AGMLG, these alterations are unlikely to play a significant role in the pathogenesis of the disease. However, by analogy with mammary Paget disease, rare cases of primary EMPD may originate in AGMLG with a subsequent upward migration of the neoplastic cells into the epidermis and possible later breach through the basal membrane. Usual ductal hyperplasia and atypical duct hyperplasia can then be regarded as earlier precursor lesions, linking both ends of the spectrum.

Mammary type tubulolobular carcinoma of the anogenital area: report of a case of a unique tumor presumably originating in anogenital mammarylike glands.

We present a case of an unusual tumor that occurred in the perianal area of a 64-year-old woman. Clinical investigation revealed no tumor elsewhere. The lesion was removed and the patient is alive without signs of metastasis or recurrence 5.5 years after surgery. Histopathologically, the neoplasm was composed of single-cell cords of uniform round to ovoid cells intermixed with round to elongated tubules showing decapitation secretion at the luminal border. The tubules were mainly composed of a single cell layer, but focally multilayered epithelium (without evidence of myoepithelial cell differentiation) was seen as well as discrete cribriform structures and intraluminal bridges. Overall, the cell cord component slightly dominated over the tubular component, and the two were intermixed. A vague targetoid arrangement of the cell cords was seen focally. Immunohistochemically, the tumor cells in both components reacted positively for E-cadherin, 34betaE12, estrogen receptors and progesterone receptor and were negative for HER2/neu (c-erbB-2). There was no evidence of myoepithelial cell differentiation with calponin. We believe that the present case is best classified as mammary type tubulolobular carcinoma and, given the location, the origin in anogenital mammary-like glands most likely.

The role of intradermal proliferation of T-cells in the pathogenesis of psoriasis

Abstract: BACKGROUND: Psoriasis is a common immune-mediated chronic inflammatory disease of the skin and joints, affecting 1-3% of the population. It is generally accepted that the pathogenesis of psoriasis involves accumulation of effector T-cells within lymph nodes and their subsequent migration into the skin through the blood system. Here we provide evidence that psoriatic plaque itself may serve as a source of inflammatory T-cells. OBJECTIVE: We examined the intradermal proliferation of T-cells and the number of effector/memory (CD45RO+) T-cells in the skin of psoriatic patients at different periods of the disease. METHODS: Skin samples were obtained from 41 patients with progressive psoriatic lesions; 18 of these patients also donated skin specimens during the remission of the disease. The control group consisted of 16 healthy subjects. Ki-67 immunohistochemical staining was applied to detect proliferating cells, CD3ε served as a T-cell marker, and CD45RA and CD45RO antibodies were utilized to discriminate between naive and effector/memory T-cells, respectively. RESULTS: Progressive psoriatic lesions demonstrated Ki67 staining both in keratinocytes and in the CD3ε+ cells of dermal infiltrate. Median count of CD45RO+ cells per microscopic field was 15 in healthy controls, 59 in patients in remission and 208 in progressive psoriatic plaques. The observed differences demonstrated high level of statistical significance. STUDY LIMITATIONS: Limited number of analyzed patients. CONCLUSION: Progressive phase of psoriasis is characterized by intradermal proliferation of T-cells. Spots of regressed psoriatic lesions contain high number of CD45RO+ cells, which are likely to render an immunological memory.