Irena E. Belousova

Sebaceous carcinoma arising in nevus sebaceus of Jadassohn: a clinicopathological study of five cases.

The authors report a small series of sebaceous carcinoma developing in nevus sebaceus of Jadassohn (also known as organoid nevus) and analyze similar cases reported in the literature. All of our patients were females (age range 57-71 years; median 60 years) who had the organoid nevus on the scalp, face, or nuchal area, the rest of which was recognized clinically and/or histologically. All sebaceous carcinomas manifested unquestionable architectural (asymmetry, invasive growth) and cytological features of a carcinoma (cellular and nuclear pleomorphism, plentiful atypical mitoses, necroses en masse), demonstrated unambiguous sebaceous differentiation in the form of mature sebocytes, and lacked other differentiations. The sebaceous carcinoma was always accompanied by other benign or malignant adnexal lesions such as sebaceoma, syringocystadenoma papilliferum, syringocystadenocarcinoma papilliferum, trichoblastoma, tricholemmoma, desmoplastic tricholemmoma, or syringoma. In three cases, prominent mucinous metaplasia of sweat ducts and glands was seen. In two of these cases, sweat ducts exhibited hyperplastic changes. The analysis of the previously published material and our cases indicates that sebaceous carcinoma arising in organoid nevus has a female predilection and tends to occur in elderly patients. It may involve any site where nevus sebaceus typically occurs. Clinically, the tumor presents as a solitary nodule, ulcerated tumor, or mass, often with a recent history of rapid growth. It may arise alone, but it occurs more frequently as part of multiple benign and malignant adnexal tumors. The lesion does not seem to be associated with Muir-Torre syndrome. The rest of organoid nevus is usually recognized both clinically and microscopically, although large tumors may overgrow and mask the nevus. The tumor seems to be a low-grade carcinoma in terms of clinical behavior.

Primary cutaneous plasmacytoma: a clinicopathological study of two cases with a long-term follow-up and review of the literature

Background:  Primary cutaneous plasmacytoma (PCP) is a rare type of cutaneous B‐cell lymphoma arising primarily in the skin and derived from clonally expanded plasma cells with a various degrees of maturation and atypia. The disease is rare with only 30 cases reported so far.

Multiple (familial) trichoepitheliomas: a clinicopathological and molecular biological study, including CYLD and PTCH gene analysis, of a series of 16 patients.

Multiple familial trichoepitheliomas (MFT) constitute an autosomally inherited syndrome possibly related to Brooke-Spiegler syndrome (BSS). Although some early studies suggested a role for the PTCH gene on chromosome 9q22.3 in the etiopathogenesis of MFT, recent studies of occasional patients with the MFT clinical phenotype identified mutations in the CYLD gene on chromosome 16q12-q13, a gene responsible for BSS. A systematic investigation of PTCH and CYLD mutations in patients with MFT has never been performed. Our main objective was to collect a reasonably large series of patients with MFT to (1) study the clinicopathological spectrum of the disease, (2) determine whether the PTCH gene is implicated in the pathogenesis of MFT, and if so (3) determine the relative frequency of CYLD and PTCH mutations, (4) establish if there may be any possible genotype-phenotype correlations, and (5) study the spectrum of somatic mutations. Clinical analysis including family histories, histopathological investigations, and molecular genetic studies were performed. There were 9 female and 7 male patients ranging in age from 11 to 63 years. They presented with multiple, small, discrete and sometimes confluent, skin-colored to pink, asymptomatic nodules preferentially located on the face, being especially prominent and confluent in the nasolabial folds and inner aspects of the eyebrows. A total of 66 conventional trichoepitheliomas (TEs) were studied microscopically. Aside from typical features of TE, some also exhibited variant morphological patterns including areas reminiscent of other benign adnexal neoplasms and melanocytic hyperplasia. In none of the 9 patients tested was a germline mutation of the PTCH gene identified. Germline CYLD mutations were detected in 6 of 13 patients tested (identical in 2 unrelated patients) including 2 novel mutations, whereas the remaining 7 individuals showed wild-type alleles. Two patients with germline wild-type CYLD showed, however, a somatic mutation in the gene (1 duplication, 1 substitution mutation). Neither CYLD nor PTCH germline mutations were found in the 5 patients in whom both genes were analyzed. MFT seems to be a phenotypic variant of BSS. The PTCH gene is rarely, if ever, involved in the pathogenesis of MFT. Absence of a germline mutation of the CYLD gene in cases harboring a somatic mutation may be explained by large deletions in the gene or by mutation in intronic sequences or in the promoter region. Considering our 5 patients with no mutation in either gene, the final possibility is that another, as yet undescribed gene (neither CYLD nor PTCH) is implicated in the pathogenesis of some patients with MFT.

Hyperplasia of Hair Follicles and Other Adnexal Structures in Cutaneous Lymphoproliferative Disorders : A Study of 53 Cases, Including So-called Pseudolymphomatous Folliculitis and Overt Lymphomas

We studied 53 cutaneous lymphoproliferative disorders, all of which manifested hair follicle hyperplasia. There were 42 cases conforming to the description of pseudolymphomatous folliculitis (PLF) and 11 cases of authentic lymphomas including mycosis fungoides, CD30+ anaplastic large cell lymphoma, diffuse large B-cell lymphoma, B-cell small cell lymphoma/leukemia, and peripheral T-cell lymphoma, not otherwise specified. All patients with PLF clinically presented with a solitary nodule preferentially involving the face. Beside hair follicle hyperplasia, the typical features were a dense infiltrate of small well-differentiated lymphocytes, lymphoplasmacytoid cells, plasma cells, and epithelioid histiocytes forming tiny granulomas. Some unusual or worrisome features recognized included eccrine/apocrine duct hyperplasia, subcutis/muscle infiltration, lymphocyte “smudging,” single file infiltration, and large atypical cells. Immunohistochemically, T-cell predominant cases dominated in the series. All 34 tested cases revealed a polyclonal pattern of κ and λ immunoglobulin (Ig) light chain expression. In 4 cases, scattered CD30+ cells were identified. Monoclonal rearrangements of T-cell receptor (TCR) and IgH genes were detected in 19 and 3 cases respectively, including 1 case with dual T-cell receptor/IgH rearrangement. Three of 30 tested cases proved positive for herpes simplex virus-1, whereas herpes simplex virus-2 always tested negative. Of 31 cases tested for Borrelia burgdorferi, 30 specimens were negative. In 9 cases, fluorescent in situ hybridization for t(11;18) and t(14;18) revealed none of the above translocations. The most common treatment modality was surgical removal. Forty patients with a mean follow-up of 3.7 years included 39 patients with no evidence of disease and 1 individual with local recurrence. The comparison of “clonal cases of PLF” and those with polyclonal population or in which clonality remained undetermined revealed no differences between the 2 groups in the clinical presentation, pathologic, and immunohistochemical features. We conclude that hyperplasia of hair follicles and other adnexa can be seen not only in the condition currently known as PLF, but also in genuine cutaneous lymphomas and may be just a happenstance secondary to a basic pathologic process.

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, 34βE12, 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.

Human papillomavirus in lesions of anogenital mammary-like glands.

Summary: Long considered as ectopic breast tissue, anogenital mammary-like glands (MLGs) have recently been suggested to represent distinctive structures located in the anogenital area. We studied 16 neoplasms of anogenital MLG for human papillomavirus (HPV) DNA using INNO-line probe assay (LiPA) HPV Genotyping kit, GP5+/6+, CP(SGB), and FAP 6085-6319 primer sets. The lesions included 3 fibroadenomas, 2 adenosis tumors, 1 invasive ductal carcinoma, 1 tubulolobular carcinoma, 2 hidradenoma papilliferum with prominent cystic change rendering a cystadenoma appearance and oxyphilic metaplasia, and 7 cases of extramammary Paget disease. All 3 fibroadenomas, both adenosis tumors, both hidradenoma papilliferum, and the tubulolobular carcinoma proved negative for HPV DNA. HPV-31 was detected by LiPA in the case of invasive ductal carcinoma. In 2 of the 7 patients with extramammary Paget disease, there was HPV DNA present in the lesional tissue, typed as HPV-6 (LiPA) and a type which was closely related to HPV-21 and HPV-24 (FAP 6085-6319), whereas the remaining 5 cases tested negative. These results coupled with those obtained from literature review suggest that HPV plays no causative role in lesions of anogenital MLG.

Paediatric cutaneous lymphomas: a review and comparison with adult counterparts.

Primary cutaneous lymphomas (CL) in children is rare. Only a few studies focused specifically on paediatric CL and therefore little is known whether primary CL in children are similar to or different from their adult counterparts with respect to the clinicopathological presentation, behaviour and prognosis. An extensive literature search using PubMed/MEDLINE from January 1995 through July 2014 was undertaken for articles reporting cases of paediatric CL. In addition, we identified 31 children with CL in our institutions. Mycosis fungoides and lymphomatoid papulosis are the two most prevalent lymphoma forms in children. A few entities of cutaneous lymphomas such as cutaneous diffuse large B‐cell lymphoma leg type, and Sézary syndrome have not been reported so far in children. Other lymphoma entities such as hydroa vacciniforme‐like lymphoma are mostly seen in certain geographic areas (Asia, Central and South America). In the paediatric population, low‐malignant indolent forms such as primary cutaneous marginal zone lymphoma and primary cutaneous follicle centre lymphoma are very rare, whereas the more aggressive forms of B‐cell lymphomas, precursor lymphoblastic lymphomas, and blastic plasmacytoid dendritic cell neoplasm are the most common forms in children, mostly involving the skin secondarily. Most paediatric lymphomas have similar clinicopathological features and course as their adults counterparts, particularly in the group of cutaneous T‐cell lymphomas. The spectrum of cutaneous B‐cell lymphomas in children significantly differs from the one in adults. Diagnostic work‐up and treatment of paediatric patients with lymphomas are best achieved in close collaboration with paediatric haematopathologists and oncologists.

Atypical histopathological features in cutaneous lymphoid hyperplasia of the scrotum.

To the Editor: It was shown by our retrospective study of 56 cases that cutaneous lymphoid hyperplasia (CLH) located on the nipple–areola complex displays atypical microscopic features that are often seen in authentic lymphomas. These include absence of germinal center polarization, reduction of mantle zones, coalescence of lymphoid follicles resulting in sheets of centroblasts reminiscent of diffuse large B-cell lymphoma, arrangement of cells in single files between collagen bundles reminiscent of cutaneous leukemia infiltrates, marked B-cell predominance, smooth muscle infiltration, angiocentric arrangement of the infiltrate and monoclonality. In our practice we encountered several cases of CLH of the scrotum, which, akin to its counterpart on the nipple, manifested similar atypical histopathological features. Although several articles dealing with CLH on the scrotum are available, none specifically emphasized this problem. Therefore, we present a series of 9 cases of scrotal CLH to demonstrate that the pseudolymphoma in this anatomic site is often associated with worrisome histology. All patients were male, their age at diagnosis ranging from 6 to 69 years (mean 20.9 years, median 10 years). Seven of the 9 patients presented with a solitary erythematous plaque or nodule on the scrotal skin ranging in size from 0.3 to 2 cm; 2 patients each had 2 nodules. The clinical diagnoses included atheroma (n = 2), nevus (n = 1), fibroma (n = 2), granuloma annulare (n = 1), pseudolymphoma (n = 1), lymphoma (n = 1), or a mere description as ‘‘a tumor’’ (n = 1). Two patients reported a tick bite 1 year and 3 years before the occurrence of the scrotal lesions. One of these 2 patients had also had cervical lymphadenopathy and fever after the bite; he had a positive serology test for Lyme borreliosis and was treated by antibiotic therapy, as was another patient who had had a history of erythema chronicum migrans 7 years

Unusual manifestation of specific cutaneous involvement by B-cell chronic lymphocytic leukemia: Spontaneous regression with scar formation

We report a patient with specific cutaneous involvement by B-cell chronic lymphocytic leukemia, who demonstrated unusual clinical features during the course of the disease, namely several spontaneous regressions of skin lesions with the formation of scars. In addition, histologically proven keratoacanthoma was found. During the follow-up period of approximately 1.5 years, the patient experienced several recurrences of skin lesions and their partial spontaneous regression. The scars persisted and remained unchanged. We hypothesize that vascular injury combined with edema could have accounted for dermal ischemia and the subsequent development of the scarring lesions.

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.