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Kaposi sarcoma (KS) is a human herpes virus-8 (HHV8) – associated vasoformative lesion affecting the skin, mucosae, and viscera. Conventional cutaneous KS manifests with patch, plaque, or nodular lesions, with each subtype exhibiting distinctive histomorphology. Recent decades, however, have revealed a broader histological spectrum of KS in the skin. Recognition of the wide range of microscopic variants of KS and their individual mimics is essential for correct diagnosis. This is enhanced by careful clinico-pathological correlation and the utilisation of appropriate ancillary investigations. The demonstration of nuclear staining for HHV8 latency associated nuclear antigen by immunohistochemistry enables confirmation of a given KS variant. Conversely, negative immunoreactivity for HHV8 is a unifying feature among the numerous dermatoses and/or neoplasms that constitute the differential diagnosis of a given KS subtype.

Endometrial carcinomas are common female genital tract malignancies. Western countries identified BRAF mutations in very few endometrial carcinomas, whilst an Eastern study documented mutations in ...

The spectrum of infectious diseases with potential skin involvement, either primary or secondary to systemic disease, is vast. Unusual host inflammatory responses may be elicited by certain pathogens, including reactions with an inherent capacity for misdiagnosis as neoplasia. Current, emerging, re-emerging and/or recently recognized pathogens or infections of major significance include carbapenem-resistant gram-negative bacterial infections, Ebola virus disease, measles, Mycobacterium lepromatosis as a second aetiological agent of leprosy, and Emergomyces africanus infection among those living with HIV/AIDS. The era of molecular microbiology has also seen recent changes in taxonomy, including Talaromyces marneffei (formerly Penicillium marneffei) and Cutibacterium acnes (formerly Propionobacterium acnes). Precise speciation by PCR on formalin-fixed, paraffin embedded tissue, however, remains a challenge despite recent advances in molecular microbiology. Finally, one must remain cognizant of the wide range of potential infective manifestations of the immune reconstitution inflammatory syndrome in HIV-infected individuals receiving antiretroviral therapy.

Endometrial carcinomas are common malignancies worldwide. Microsatellite instability is often identified in endometrioid endometrial carcinomas (EECs) and in most Lynch syndrome (LS) associated tum...

In 2013, a novel thermally dimorphic fungal pathogen was described to cause disseminated disease among persons living with advanced HIV/AIDS in South Africa. Although the organism was initially described as an Emmonsia-like fungus, it is now known to belong to a new genus of thermally dimorphic fungi and was recently named Emergomyces africanus. There is considerable clinical and histopathological overlap between emergomycosis and histoplasmosis. This review addresses taxonomic, clinical, diagnostic, and therapeutic aspects of Es. africanus disease, a condition which has, to date, only been reported from southern Africa.

Malignant chondroid syringoma (MCS, malignant mixed tumour) is a rare neoplasm typically arising on the extremities and trunk. We are report 2 unique cases of MCS, one occurring on the scalp of a 78-year-old man and the other on the trunk of a 72-year-old woman. Both tumours harboured malignant epithelial and malignant mesenchymal components. The latter was represented by liposarcoma in the first case. The malignant components of the second tumour comprised spindle cell squamous cell carcinoma (SCC) and osteosarcoma. Origin from a pre-existing benign chondroid syringoma was clearly evident in both neoplasms. The presence of heterologous malignant mesenchymal components, however, is hitherto unreported in the context of MCS, while a spindle cell SCC component is exceptionally rare. The 2 cases presented herein highlight an expanded morphological spectrum of MCS, with resultant blurring of the boundaries between MCS and cutaneous carcinosarcoma.

Keratolytic winter erythema (KWE) is a rare autosomal dominant keratoderma affecting primarily the palms and soles, manifesting with recurrent waves of erythema followed by epidermal peeling. The condition is so named in view of its anecdotal worsening during the winter months. It is highly penetrant but shows considerable individual clinical variability, waning and reappearing throughout the life course. Histologically, early established lesions of KWE manifest with degenerative changes involving the Malpighian layer, with associated absence of the stratum granulosum. The damaged zone undergoes parakeratotic transformation and subsequent centrifugal ejection. Thick peeling occurs when the stratum corneum eventually separates off as a result of a keratolytic split occurring above, through or below the parakeratotic zone. Reconstitution of the stratum granulosum ensues. KWE is caused by a duplication of an intergenic enhancer element upstream of the cathepsin B gene on chromosome 8. This leads to the upregulation of cathepsin B in the stratum granulosum and subsequent peeling of the epidermis as the end result. With elucidation of the molecular pathology of KWE, new therapeutic approaches to KWE may be considered.

Background The global mortality from HIV and the cutaneous burden of infective, inflammatory and malignant diseases in the setting of AIDS have significantly declined following the advent of highly active antiretroviral therapy. Regrettably, there has been a contemporaneous escalation in the incidence of adverse cutaneous drug reactions (ACDR), with studies attesting that HIV-positive individuals are a hundred times more susceptible to drug reactions than the general population, and advanced immunodeficiency portending an even greater risk. Several variables are accountable for this amplified risk in HIV. Summary Adverse reactions to trimethoprim-sulfamethoxazole are the most common, increasing from approximately 2-8% in the general population over to 43% amongst HIV-positive individuals to approximately 69% in subjects with AIDS. Antituberculosis drugs and antiretrovirals are also well-known instigators of ACDR. Cutaneous reactions range from mild morbilliform eruptions to severe, life-threatening manifestations in the form of Stevens-Johnson syndrome/toxic epidermal necrolysis. Histological features vary from vacuolar interface changes to full-thickness epidermal necrosis with subepidermal blister formation. A precipitous diagnosis of the ACDR, clinically and histologically if necessary, together with the isolation of the causative drug is critical. The identification process, however, is often complex and multifaceted due to polypharmacy and inconclusive data on which drugs are the most likely offending agents, especially against the background of tuberculosis co-infection. Key messages Whilst milder cutaneous reactions are treated symptomatically, severe reactions mandate immediate treatment discontinuation without rechallenge. Further studies are required to establish safe rechallenge guidelines in resource-limited settings with a high HIV and tuberculosis prevalence.

The rickettsiae are a diverse group of vector-borne zoonotic bacterial pathogens. The two common spotted fever diseases in existence in southern Africa are boutonneuse fever-like tick bite fever (TBF), caused by Rickettsia conorii, and African TBF, caused by R. africae. This review addresses demographic, epidemiological, clinical, diagnostic, therapeutic, and preventive aspects of TBF in the southern African context, including a discussion of the dermatopathological findings and potential diagnostic pitfalls.

Scleroderma is a rare complication of carcinoid syndrome and is usually encountered in the setting of a metastatic primary neuroendocrine tumour of the distal ileum. Associated endocardial fibrosis is a frequent finding and the condition carries a poor prognosis. We report a case of scleroderma occurring in a 72-year-old female with metastatic neuroendocrine carcinoma and associated pericardial fibrosis. The use of an alternative nomenclature such as "scleroderma-like" or "sclerodermoid" disease is proposed in order to emphasise its distinction from true idiopathic scleroderma, despite the histopathological similarities on skin biopsy.

Endometrial carcinoma is the most frequently occurring female genital tract malignancy in developed nations, with a rising annual incidence. Endometrioid endometrial carcinoma (EEC), the most common histological variant, differs in morphologic and molecular characteristics from serous carcinomas but morphological distinction of high-grade EECs from serous carcinomas may prove difficult. Thus, molecular categorization of tumors may allow for better tumor classification with greater insight into the underlying biology of endometrial carcinomas with new therapeutic options. Microsatellite instability (MSI) is a commonly occurring molecular aberration in EECs and has been identified in most Lynch Syndrome (LS) associated tumors. This tumor syndrome predisposes afflicted individuals to a myriad of tumors including endometrial carcinoma. Herein, the molecular signature of endometrial tumors as well as LS, and its clinical manifestations are reviewed. Understanding of the pathogenetic pathways allows for greater comprehension of occurrences at a molecular level which are then appreciated at a cellular and tissue level, by the histopathologist. The molecular classification of endometrial tumors allows for further targeted therapeutic options for affected patients. Screening tests for patients with suspected LS enables surveillance of other tumors in the affected patient and her family with the potential to decrease morbidity and mortality. It is envisioned that this overview will allow for enhanced comprehension of genetic pathways by practicing pathologists, oncologists, gynecologists and other members of the multidisciplinary team, all of whom are involved in the management of the patient with an endometrial malignancy.

Contains fulltext : 174194.pdf (Publisher’s version ) (Open Access) Keratolytic winter erythema (KWE) is a rare autosomal-dominant skin disorder characterized by recurrent episodes of palmoplantar erythema and epidermal peeling. KWE was previously mapped to 8p23.1-p22 (KWE critical region) in South African families. Using targeted resequencing of the KWE critical region in five South African families and SNP array and whole-genome sequencing in two Norwegian families, we identified two overlapping tandem duplications of 7.67 kb (South Africans) and 15.93 kb (Norwegians). The duplications segregated with the disease and were located upstream of CTSB, a gene encoding cathepsin B, a cysteine protease involved in keratinocyte homeostasis. Included in the 2.62 kb overlapping region of these duplications is an enhancer element that is active in epidermal keratinocytes. The activity of this enhancer correlated with CTSB expression in normal differentiating keratinocytes and other cell lines, but not with FDFT1 or NEIL2 expression. Gene expression (qPCR) analysis and immunohistochemistry of the palmar epidermis demonstrated significantly increased expression of CTSB, as well as stronger staining of cathepsin B in the stratum granulosum of affected individuals than in that of control individuals. Analysis of higher-order chromatin structure data and RNA polymerase II ChIA-PET data from MCF-7 cells did not suggest remote effects of the enhancer. In conclusion, KWE in South African and Norwegian families is caused by tandem duplications in a non-coding genomic region containing an active enhancer element for CTSB, resulting in upregulation of this gene in affected individuals.

Chronic infection with hepatitis B virus (HBV) remains a problem of global significance and improving available treatment is important to prevent life-threatening complications arising in persistently infected individuals. HBV is susceptible to silencing by exogenous artificial intermediates of the RNA interference (RNAi) pathway. However, toxicity of Pol III cassettes and short duration of silencing by effectors of the RNAi pathway may limit anti-HBV therapeutic utility. To advance RNAi-based HBV gene silencing, mono- and trimeric artificial primary microRNAs (pri-miRs) derived from pri-miR-31 were placed under control of the liver-specific modified murine transthyretin promoter. The sequences, which target the X sequence of HBV, were incorporated into recombinant hepatotropic self-complementary adeno-associated viruses (scAAVs). Systemic intravenous injection of the vectors into HBV transgenic mice at a dose of 1 × 1011 per animal effected significant suppression of markers of HBV replication for at least 32 weeks. The pri-miRs were processed according to the intended design, and intrahepatic antiviral guide sequences were detectable for 40 weeks after the injection. There was no evidence of toxicity, and innate immunostimulation was not detectable following the injections. This efficacy is an improvement on previously reported RNAi-based inhibition of HBV replication and is important to clinical translation of the technology.

A large proportion of patients diagnosed with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) will develop cutaneous lesions over the course of their disease. The broad spectrum of disorders with skin involvement includes inflammatory and vesiculobullous dermatoses, infective conditions, adverse drug reactions, and neoplastic proliferations, some of which are AIDS-defining. The introduction of highly active antiretroviral therapy (HAART) and subsequently combination antiretroviral therapy (cART) has led to the emergence of the immune reconstitution inflammatory syndrome (IRIS), a condition which is frequently associated with cutaneous manifestations. Although many HIV-/AIDS-related skin disorders are largely a source of morbidity and can be readily managed on an outpatient basis, certain conditions are severe and potentially life-threatening, necessitating hospitalization. Dermatopathologists who are exposed to histologic specimens from the latter group of patients in particular are required to have a sound working knowledge of HIV-/AIDS-associated cutaneous pathology, and an integrated diagnostic approach. Detailed clinicopathologic correlation, which encompasses knowledge of the patient’s treatment status and CD4 T-cell count, is essential for accurate diagnosis. This chapter focuses primarily on the noninfective complications and dominant neoplastic proliferations associated with HIV/AIDS.

Giant congenital melanocytic naevi (GCN) are rare, disfiguring lesions which carry a significant risk of malignant transformation. Melanoma is the most common malignancy documented in association with these lesions. Although exceedingly rare, other malignant neoplasms, including mesenchymal tumours such as rhabdomyosarcoma (RMS), may complicate GCN. This report documents a fatal embryonal RMS arising in a GCN on the distal left lower limb of a 4-month-old female infant, who had ipsilateral inguinal lymph node metastases at the time of presentation. To date there have been only 7 prior reports in the English literature of RMS complicating GCN. Differential diagnoses include small cell melanoma, rhabdoid melanoma, and melanoma with divergent RMS differentiation. A distinction between the latter and de novo RMS arising in GCN may have potential prognostic and therapeutic implications.

Patient: Female, 44 Final Diagnosis: Acral peeeling skin syndrome Symptoms: Recurrent skin exfoliation Medication: — Clinical Procedure: Skin biopsy Specialty: Dermatology Objective: Rare disease Background: Acral peeling skin syndrome is a rare autosomal recessive disorder in which skin exfoliation is limited to the hands and feet. While it typically manifests from early childhood, in this first reported case from South Africa, the patient did not manifest clinically until the fourth decade of life. Case Report: A 44-year-old woman of African descent, 1 of a set of non-identical twins, presented with recurrent episodes of skin peeling of the upper and lower limbs. The first episode occurred 4 years prior, followed by perennial skin peeling during the spring seasons. She was not on treatment for any chronic disease and reported no exposure to chemicals or other irritants. The family, including the non-identical twin sister, has no history of skin disorders and the patient’s HIV antibody test was negative. At presentation, physical examination revealed ongoing exfoliation with new skin formation on the palms and soles. The mucous membranes and nails were spared. Other systems were normal. Skin biopsy taken from the palms confirmed peeling skin syndrome. The patient was managed with topical aqueous cream and analgesics. She was briefly counseled on the nature and prognosis of the disease, and referred for genetic testing and counseling. On follow-up, she continues to have skin peeling once or twice a year. Conclusions: This first reported case of this rare disease in South Africa contributes to the growing body of literature on the disease and highlights the need for clinicians to be aware of its variable clinical onset.

Mixed tumor, eccrine type, is a rare cutaneous adnexal neoplasm, mostly reported as isolated case reports. A systematic analysis of its histopathologic and immunohistochemical features has not previously been performed on a large series. The purpose of our investigation was to study a large number of cutaneous eccrine mixed tumors so as to fully characterize the entire spectrum of changes in the epithelial and stromal components, with an emphasis on unusual histopathologic features that may represent a diagnostic pitfall. This article reports a light microscopic and immunohistochemical study of 50 cases of eccrine mixed tumor, complemented by a literature review. Our study identified some unusual histopathologic features, thus extending the morphologic spectrum of this neoplasm. These included prominent cribriform areas, clear cell change, pseudorosette structures, prominent osseous metaplasia, and physaliphorous-like cells. Most of these features have not been previously recorded in eccrine mixed tumors and may represent a potential diagnostic pitfall.

Melanomas possess a remarkable capacity for morphological diversity and even divergent differentiation. Classification of these unusual variants is based on the recognition of a specific growth pattern (e.g. pseudoglandular, angiomatoid) or a unique cytological attribute (e.g. clear cell, balloon cell, rhabdoid). Unusual morphology may be encountered in primary, metastatic or recurrent tumours alike. Some variants are so named because of their ability to mimic benign melanocytic proliferations (e.g. naevoid, Spitzoid). Most are not associated with specific prognostic differences. Instead, their importance resides in the potential for confusion with a wide range of benign and malignant neoplasms. Diagnosis of melanoma is less problematic when lesions are pigmented and/or if there is an intra-epidermal component. Purely dermal neoplasms, however, pose a diagnostic challenge, especially when amelanotic. Immunohistochemistry is often invaluable in confirming the diagnosis of melanoma and excluding the histopathological differential diagnosis associated with several unique variants discussed in this review.

Two cases of segmental lichen aureus with a response to topical 0.1% methylprednisolone aceponate ointment are reported. A 9-year-old child and a 23-year-old man showed complete resolution of their lesions following treatment with the latter after 7 months and 4 months, respectively. Lichen aureus is a rare form of the pigmented purpuric dermatoses characterized by golden-brown and lichenoid macules and papules, most often on the lower extremities. Segmental presentations have seldom been described. Histology showed a lichenoid infiltrate with extravasation of red blood cells and haemosiderin deposition. The aetiology is unclear and treatment is disappointing. We report an uncommon segmental presentation of lichen aureus with resolution of the lesions after treatment with a topical corticosteroid.

Mucocutaneous lesions are a frequent manifestation of human immunodeficiency virus (HIV) infection and/or the acquired immunodeficiency syndrome (AIDS) in adult and paediatric patients alike. These include a wide variety of infective disorders, inflammatory dermatoses and adverse drug reactions. Although there is considerable overlap in the spectrum of skin disease in both groups, significant differences exist. Oral candidiasis, which implies marked immune deficiency in adults with AIDS, may occur without severe CD4+ T-cell depletion in children. Infective and inflammatory disorders such as oral hairy leucoplakia, bacillary angiomatosis and HIV-associated eosinophilic pustular folliculitis are exceedingly uncommon in children. Kaposi sarcoma is encountered far less frequently in children, and non-Hodgkin lymphoma in mucocutaneous sites is rarely seen. Stigmata of concomitant nutritional deficiencies are often observed in children. This review gives an overview of this spectrum of disease. The paucity of literature on the immune reconstitution inflammatory syndrome in the paediatric context is emphasized.

Cutaneous sebaceous neoplasia is known to exhibit a high degree of DNA mismatch repair (MMR) deficiency leading to microsatellite instability and these tumors can be markers of the Muir-Torre syndrome and internal malignancy. Other tumors, such as colonic carcinoma, show tendencies toward particular histologic features and sites of involvement correlating with MMR deficiency. There are few comprehensive studies of unselected cutaneous sebaceous neoplasms. To address this gap in knowledge, we examined 94 sebaceous neoplasms from 92 patients and 17 sebaceous hyperplasia controls using immunohistochemistry for MLH1, MSH2, and MSH6. Our results indicate that MMR deficiency is significantly associated with anatomic location (more frequently in the trunk and extremities as compared with head and neck), tumor type (more often in adenoma compared with carcinoma within the head and neck region), and architecture (keratoacanthomalike). No correlation between cystic change and MMR deficiency was noted. Cutaneous sebaceous neoplasia has tendencies toward certain tumor types and anatomic distribution based on MMR status analogous to that seen in colonic carcinomas and other tumors. These may be helpful indicators for further workup for the Muir-Torre syndrome.

Primary cutaneous apocrine carcinoma is a rare malignancy. This study of 24 examples suggests that the prognosis is not always poor and that grading criteria devised for breast carcinoma may have utility in this group of malignancies. Furthermore, steroid receptor expression should be investigated in these tumors, particularly if a tumor is unlikely to be controlled by surgery alone.

Dermatological disorders are a frequent presenting feature of HIV infection and/or AIDS. More than 90% of HIV-infected patients will suffer from one or more skin diseases during the course of their illness. This trend is reflected in the increasing number of skin biopsies from HIV-positive patients in those parts of the world where HIV infection/AIDS is highly prevalent. Histopathologists are therefore required to possess a working knowledge of the broad spectrum of cutaneous manifestations of HIV infection. These include the range of dermatoses that are specific to HIV infection, the more common dermatoses occurring with greater frequency (or modified by) HIV infection/AIDS, the spectrum of infectious diseases (often opportunistic) caused by viruses, bacteria, fungi, protozoa and even arthropods, and neoplastic conditions such as Kaposi sarcoma and B-cell non-Hodgkin lymphoma. The risk for adverse skin reactions to certain drugs is also greatly increased. Although the introduction of highly active antiretroviral therapy has resulted in a dramatic decrease in opportunistic infections, several of these drugs may result in adverse reactions in the skin. Skin biopsies play a vital diagnostic role when different diseases present with clinically similar skin lesions. Biopsy material should always be examined carefully to exclude dual pathology. The diagnosis may need to be confirmed with histochemical and immunohistochemical stains, and/or molecular studies. Where indicated, additional biopsies for microbiological culture should always be recommended. The examination of multiple serial sections often proves invaluable. A diagnostic approach is given based on the predominant histological reaction pattern, with an emphasis on clinicopathological correlation.

Aim: Squamous differentiation in eccrine porocarcinoma (EPC) is an unusual phenomenon that has rarely been reported in the literature. This study describes the clinical and pathological findings in a series of 21 cases of EPC showing extensive squamous differentiation. Methods: The H&E-stained sections, epithelial membrane antigen and carcinoembryonic antigen immunohistochemical stains were reviewed for each case. The following variables were examined: age, gender, race, site and size of the EPC. The prevalence of other cutaneous lesions and/or underlying systemic disease was also documented. Results: There was an almost equal gender distribution. Mean age was 61.5 years and the average tumour size was 46.5 mm. An inordinately large number (10/21, 48%) of EPCs occurred in black patients. The tumours were located at various sites with the extremities predominating (10/19, 53%). Seven patients developed other sun-induced skin tumours, three patients were renal transplant recipients, and two patients were HIV-positive, one of whom also suffered from albinism. Six of the 11 patients in whom follow-up was available had an adverse outcome: local recurrence developed in one patient, one patient developed nodal metastases, and one patient experienced both local recurrence and nodal metastases, and of the three patients who died of disease, two developed distant metastases. Conclusion: The findings suggest a possible role for ultraviolet radiation and chronic immunosuppression in the induction of malignant squamous differentiation in a subset of EPCs. Further reports on this histological variant of EPC are required to determine whether a pathogenetic link does indeed exist or whether these tumours simply represent a unique variant of squamous cell carcinoma with divergent acrosyringial differentiation.

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."

Pagetoid reticulosis (PR) is a low-grade primary cutaneous T-cell lymphoma that usually presents as a solitary, slowly enlarging erythematous or hyperkeratotic plaque on the distal areas of the extremities. Histopathologically, it is characterized by a dense, band-like infiltrate of atypical lymphocytes with prominent epidermotropism within a hyperplastic epidermis, and immunophenotypic studies show in most cases, a CD4-positive T-helper phenotype for the neoplastic lymphocytes. We describe an African man with a more than 20-year history of an acral lesion of PR, which was histopathologically characterized by lymphocyte immunophenotype consisting of CD8- and CD30-positive cells. We discuss the differential diagnosis with other primary cutaneous lymphoproliferative disorders showing similar immunophenotype. This case shows that CD30-positive PR should be included as a rare variant within the spectrum of CD30-positive primary cutaneous lymphoproliferative disorders. As in other primary cutaneous CD30-positive lymphoproliferative processes, lesions of CD30-positive PR show an indolent course and a benign biological behavior.

Background Papular and follicular eruptions, such as papulopruritic eruption, eosinophilic folliculitis, and infective folliculitis, are relatively common disorders in patients infected with the human immunodeficiency virus (HIV). These conditions may show considerable clinical overlap. Objective To assess the relative proportion of pruritic papular cutaneous eruptions in South Africans with HIV-associated dermatoses, and to correlate the clinical and histologic features of these lesions. Methods The clinical and histologic features of papular follicular eruptions were correlated in 40 consecutive black HIV-positive patients who underwent skin biopsy. Results The clinical features were similar in all patients and consisted of widespread papules and pustules involving the face, limbs, and trunk. The most common histologic finding was acute suppurative folliculitis, seen in 27 patients (67.5%). In most cases, no cause was found for the suppuration. Papulopruritic eruption of HIV was diagnosed in six patients (15%), HIV-associated eosinophilic folliculitis in four (10%), Pityrosporum folliculitis in two (5%), and acne in one (2.5%). Concordance between the initial clinical diagnosis and the final histopathologic diagnosis was achieved in only 27.5% of cases. Conclusion Skin biopsy remains an important adjunct to the correct diagnosis and classification of papular and follicular eruptions in HIV-positive patients.

BACKGROUND Gliomatosis of the brain or spinal cord is an infiltrating glial neoplasm that shows widespread invasion of the central nervous system with relative sparing of the underlying cytoarchitecture. Acceptance of the idea that the condition represents a distinct entity remains controversial in the absence of conclusive pathogenetic data. The clinico-pathological problems and difficulties in the ante-mortem diagnosis as well as the clinical and pathological similarities to infective lesions are evaluated. METHODS AND RESULTS Three cases of cerebral and spinal gliomatosis are presented that clinically mimicked infective lesions and were diagnosed and treated as such. The correct diagnosis in each case was only made at post-mortem examination. The ante-mortem diagnosis of this rare tumor remains difficult owing to poor correlation of clinical, neuroradiological, and neuropathological findings. CONCLUSION Gliomatosis of the brain and spinal cord may simulate infective lesions owing to difficulty in ante-mortem diagnosis because of vagueness of physical, radiological, and pathological findings. It is a diagnostic pitfall particularly in our setting where there is a high incidence of HIV/AIDS and patients often present with opportunistic infections such as mycobacterial, fungal, and/or viral infections, which show an atypical clinical picture and radiological findings. Multifocal neurologic deficit with noncontrast enhancing lesions that show diffuse contiguous involvement with overall preservation of the spinal or cerebral architecture and do not respond to infective treatment could suggest a diagnosis of gliomatosis cerebri.

Pemphigus vulgaris is an autoimmune disease characterized by acantholytic blisters and erosions involving the oral mucosa, skin, and less frequently other mucosal surfaces. Although the cytology of scrapings from the cutaneous and oral lesions has been well-documented, there are relatively few reports in the literature of the cytologic appearance of pemphigus on cervicovaginal smears. This report documents a case of pemphigus involving the cervix, in which the diagnosis was not known at the time of the cervical smear and biopsy. The cytologic features of this case and those in the literature are described in detail, highlighting the necessity of awareness of the disease and its presentation on cervicovaginal smears, in preventing an overdiagnosis of neoplasia.

Adenoid cystic carcinomas (ACCs) and adenoid basal carcinomas (ABCs) are rare neoplasms of the uterine cervix that are currently regarded as distinct clinicopathologic entities. Accurate distinction between ABCs and ACCs is of clinical importance because of differences in their biological behavior. This study compares the morphologic, mucin, and immunohistochemical profiles of 18 cervical ACCs, 8 ABCs, and 1 combined ABC-ACC. Serial sections from the 27 cases were stained with hematoxylin and eosin, periodic acid-Schiff-diastase, mucicarmine, and alcian blue and subjected to a panel of immunoperoxidase markers, namely, MNF116, CAM 5.2, CK7, CK20, epithelial membrane antigen, carcinoembryonic antigen (CEA), S-100, HHF 35, laminin, and type IV collagen. One ACC was also examined ultrastructurally. Almost all patients were postmenopausal black women. The distinction between ABC and ACC was best made morphologically. Divergent epithelial differentiation was seen in 18 cases (11 ACCs, 6 ABCs, and 1 ABC-ACC). Six cases with intact surface epithelium showed a high grade squamous intraepithelial lesion. There was no significant difference in mucin staining. Both tumor types had a similar immunohistochemical profile, apart from type IV collagen and laminin staining, which occurred exclusively in relation to the extracellular basement membranelike material in the ACC. Eleven ACCs and three ABCs were S-100-positive, including the respective ACC and ABC components of the combined ABC-ACC. Eight of the S-100-positive neoplasms with ACC morphology also stained with HHF 35, suggesting myoepithelial differentiation. The latter was confirmed in one ACC examined ultrastructurally. The similar clinical profiles, apart from the different biological behavior, capacity for divergent differentiation, and the occurrence of ABC areas in some ACCs and vice versa suggest that these tumors may share a common histogenesis, forming part of a morphologic and biologic spectrum of basaloid cervical neoplasms of putative "reserve cell" origin. Circumstantial evidence suggests that ABC may be a precursor of cervical ACC.

Mucinous carcinoma may present at various sites, including the breast and the gastrointestinal tract. Rarely, such tumors arise within the skin. Comparatively, breast lesions are relatively common and usually associated with a good prognosis. When pure, they are typically estrogen (ER) and progesterone receptor (PR) positive and responsive to tamoxifen. The authors studied 12 mucinous carcinomas of the skin and compared the morphology with that of typical mammary lesions. The authors also evaluated for expression of estrogen receptor, progesterone receptor, and the mucus-associated peptides of the trefoil factor family (TFF), TFF1 (formerly pS2) and TFF2 (formerly SP), using immunohistochemistry. The localization of mRNAs for TFF1, TFF2, and TFF3 (formally ITF) was also studied in a subset of three tumors, using in-situ hybridization with S35 labeled riboprobes. The Grimelius stain was used to look for evidence of neuroendocrine differentiation. Eight resembled type A mucinous carcinomas of the breast, two resembled type B, and one had composite features. The 12th was a papillary neoplasm. The two type B tumors exhibited argyrophilia. All showed strong nuclear staining with the estrogen receptor antibody but a more varied pattern with antibodies to progesterone receptor and TFF1. None labeled for TFF2. The detection of TFF1 in mammalian skin is a novel finding. Cutaneous mucinous carcinoma shows strong similarities to its mammary counterpart, including expression of estrogen receptor, TFF1, and TFF3 mRNA. These observations suggest that some mucinous carcinomas of the skin might respond to antiestrogenic therapies.

SummaryThis study investigated the role of human papillomavirus (HPV) in adenoid basal carcinoma, a rare neoplasm of the uterine cervix. Nine archival paraffin-embedded tumors were analyzed with non-isotopic in situ hybridization (NISH) for HPV types 6. 11, 16, 18, 31, and 33 using digoxigenin-label

AIM: To investigate the role of human papillomavirus (HPV) in adenoid cystic carcinoma of the uterine cervix. METHODS: Eleven archival, paraffin wax embedded specimens were analysed by non-isotopic in situ hybridisation (NISH) for HPV types 6, 11, 16, 18, 31, and 33 using digoxigenin labelled probes. The polymerase chain reaction (PCR) was carried out on each of the cases using consensus primers to HPV. RESULTS: A total of eight adenoid cystic carcinomas harboured the HPV genome by NISH, of which five were PCR positive. Integrated HPV 16 DNA was demonstrated in seven of the eight NISH positive cases. One adenoid cystic carcinoma showed integrated HPV 31. HPV DNA was not detected in the three remaining cases. CONCLUSIONS: Integrated high risk HPV genome, in particular type 16, is associated with this uncommon type of primary cervical cancer.

A large percentage of patients with HIV/AIDS will develop dermatological complications. Consequently, all practising clinicians and pathologists in regions with a high prevalence of HIV/AIDS must be familiar with the diverse cutaneous manifestations of the disease. This paper highlights the fact that biopsy material in this clinical context may occasionally reveal more than one pathological process. The potential spectrum includes two or more infections in a single skin biopsy (e.g., herpes simplex and cytomegalovirus infection), neoplastic lesions containing infective organisms (Kaposi sarcoma (KS) and cryptococcosis), dermatoses in association with neoplastic lesions (e.g., KS and interface dermatitis), or more than one dermatosis in a given specimen (e.g., papulopruritic eruption and nodular prurigo). Rare biopsies may even demonstrate triple pathology. The importance of careful examination of skin biopsies in this clinical context is emphasised. Failure to recognise an undiagnosed concomitant opportunistic infective pathogen could have potentially disastrous consequences for the patient.

Background: Kaposi sarcoma (KS) is a low-grade angioproliferative neoplasm derived from lymphatic endothelium. Lesions progress from early patch stage into plaques that ultimately form tumor nodules. Several histological variants of KS have been described. The aim of this study is to describe 5 new histopathologic variants of cutaneous KS. Method: Skin biopsy material submitted to a South African dermatopathology practice diagnostic of KS was reviewed. Formalin-fixed, paraffin-embedded tissue was routinely processed and stained with hematoxylin and eosin. Confirmatory immunohistochemical stains included CD31 and latent nuclear antigen-1 (human herpesvirus 8). Results: All biopsies were procured from HIV-positive patients with a clinical diagnosis of cutaneous KS tumor. Five distinct histologic KS variants, not previously well characterized in the literature, were identified including glomeruloid KS, telangiectatic KS, ecchymotic KS, KS with myoid nodules, and pigmented KS. Tumor cells in all of these variants were immunoreactive for CD31 and latent nuclear antigen-1. Conclusions: These unique cases highlight the ability of KS to exhibit variable histomorphology. Their clinical significance requires further study. Dermatopathologists should be aware of these newly described variants to avoid the potential for their misdiagnosis.

Summary Exogenous (cosmetic) ochronosis is caused by the long term use of skin-lightening creams containing hydroquinone. Three cases of systemic sarcoidosis with cutaneous sarcoidal granulomas, which developed on ochronotic skin were last described by Jacyk in 1995. Dogliotti and Leibowitz previously reported cases of granulomatous ochronosis with sarcoid-like histological changes but with no associated systemic sarcoidosis. We report two additional cases of cutaneous sarcoidal granulomas, which developed on a background of cosmetic ochronosis in patients recently diagnosed with systemic sarcoidosis.

The authors present a series of 24 malignant neoplasms arising in preexisting benign spiradenoma (20), cylindroma (2), and spiradenocylindroma (2). Nineteen patients (12 females, 7 males; age range, 41 to 92 y) had a solitary neoplasm (size range, 2.2 to 17.5 cm; median 4 cm), whereas the remaining 5 (4 females, 1 male; age range, 66 to 72 y) manifested clinical features of Brooke-Spiegler syndrome (BSS), an autosomal dominantly inherited disease characterized by widespread, small, benign neoplasms on which background larger malignant lesions appeared. Microscopically, all cases showed the residuum of a preexisting benign neoplasm. The malignant components of the lesions were variable and could be classified into 4 main patterns, occurring alone or in combination: 1) salivary gland type basal cell adenocarcinoma-like pattern, low-grade (BCAC-LG); 2) salivary gland type basal cell adenocarcinoma-like pattern, high-grade (BCAC-HG); 3) invasive adenocarcinoma, not otherwise specified (IAC-NOS); and 4) sarcomatoid (metaplastic) carcinoma. In 1 case of IAC-NOS, an in situ adenocarcinoma was also found, presumed to have evolved from an adjacent adenomatous and atypical adenomatous component. Cases harboring a sarcomatoid carcinoma featured a malignant epithelial component composed of varying combinations of BCAC-HG, BCAC-LG, IAC-NOS, or squamous cell carcinoma, whereas the sarcomatoid component appeared as either a pleomorphic or spindle-cell sarcoma. Additionally, in 2 cases there were foci of heterologous chondrosarcomatous differentiation and in 1 case there was rhabomyosarcomatous differentiation. Of the 21 patients with available follow-up (range, 3 mo-15 y; average 4.8 y; median 3.5 y), 10 were without evidence of disease, 1 was alive with metastatic disease, 1 was alive with BSS, 3 developed local recurrences, 4 had died of disease, and 2 were dead of other causes. The histologic pattern of the malignant neoplasm correlated to some extent with the clinical course. BCAC-LG neoplasms showed a less aggressive course, with local recurrences but no distant metastases, whereas the BCAC-HG neoplasms typically followed a highly aggressive course resulting in the death 3 of 6 patients with BCAC-HG. Patients with sarcomatoid carcinoma had a relatively good survival. Molecular genetic investigations revealed no mutations in the CYLD gene in the 4 sporadic cases investigated. One patient with BSS revealed a novel missense germline mutation in exon 14 (c. 1961T>A, p. V654E), whereas a living descendant of another deceased patient demonstrated a recurrent nonsense germline mutation in exon 20 (c. 2806C>T, p. R936X). Given the morphologic diversity and complexity of the neoplasms in question, we propose using a more specific terminology with the precise description of the neoplasm components, rather than generic and less informative terms such as "spiradenocarcinoma" or "carcinoma ex cylindroma."

Aim:To determine if human papillomaviruses (HPVs) play a role in the histogenesis of adenosarcomas of the uterine cervix.Methods:Nine archival cases of primary cervical adenosarcoma were studied. The HPV status of the nine histologically proven tumours was investigated by non-isotopic in situ hybridisation (NISH) and PCR. NISH was performed using digoxigenin labelled probes to HPV types 6, 11, 16, 18, 31 and 33. PCR used GP5+/GP6+ primers to the HPV L1 gene.Results:Neither the benign epithelial components nor the malignant stromal components of the 9 neoplasms harboured nuclear NISH signals for the HPV types investigated. Amplimers of the HPV L1 gene were not detected by PCR in any of the tumours studied.Conclusion:HPVs do not appear to play an aetiological role in cervical adenosarcomas. This suggests that a different histogenetic pathway for this rare tumour type must exist.

Lymphoepithelial carcinoma (LEC) is a rare category of malignant neoplasms that share morphologic features with undifferentiated nasopharyngeal carcinoma, which can be regarded as the prototype Epstein-Barr virus (EBV)–positive epithelial neoplasm. A similar association with EBV is emerging for LEC of the oral cavity, which appears to be strongly influenced by the ethnic origin of the patient. A rare case of primary LEC of the lower lip in a 73-year-old Caucasian man is described. The tumor showed a striking microscopic resemblance to undifferentiated nasopharyngeal carcinoma (lymphoepithelioma) with features of a syncytial growth pattern, large undifferentiated tumor cells with vesicular nuclei, prominent eosinophilic nucleoli, and a dense intratumoral lymphocytic infiltrate. There was, however, no evidence of EBV infection of the tumor cells by immunohistochemistry and polymerase chain reaction, suggesting that EBV probably does not play a role in the pathogenesis of LEC of the lip in Caucasian patients.

Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms. We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas. Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin. This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.

Ganglioneuroblastic differentiation in malignant melanomas is an exceedingly rare event. Although there has been a single report of this occurrence in a metastatic melanoma, divergent ganglioneuroblastic differentiation has not been documented previously in a primary cutaneous lesion of melanoma. The present report describes an unusual case of invasive melanoma arising on the lower leg of a 61-year-old woman. The 16.9-mm thick tumor showed extensive ganglioneuroblastic differentiation, which was confirmed both immunohistochemically and ultrastructurally. Although the prognostic significance of this observation remains uncertain, the unique case reaffirms the potential morphologic diversity of melanomas and suggests a shared histogenetic origin from a common neural crest derivative.

Rosai-Dorfman disease (RDD) is a rare but distinctive clinicopathologic entity of unknown etiology affecting lymph nodes as well as extranodal sites. Although cutaneous involvement in RDD is common, purely cutaneous disease is rare and not well documented. We report 22 patients with cutaneous and superficial subcutaneous RDD. The lesions presented as papules and nodules, often with discoloration (9/22) and frequent multifocality (13/22), without predilection for a specific site of the body. Age distribution was wide and ranged from 15 to 68 years, with a median of 43.5 years. Of the 17 patients for whom information on racial background was available, 7 were Asian, 8 were white, and 2 were black, with a marked female predominance (2:1). The lesions resolved in 6 of 13 patients for whom follow-up data were available, regardless of the treatment given. Lesions persisted or recurred in 7 patients. Histologically, the lesions are invariably characterized by a proliferation of polygonal S100-positive histiocytes showing emperipolesis and a mixed inflammatory infiltrate. This study characterizes the histologic spectrum of cutaneous RDD in regard to variation in the numbers of typical S100-positive histiocytes and emperipolesis, variation in the quality and quantity of the inflammatory response, and the degree of stromal fibrosis, which resulted in a strikingly storiform growth pattern in six lesions and a lobulated pattern in two lesions. Whereas the clinical as well as histologic appearance of the cutaneous and subcutaneous lesions in the purely extranodal forms of RDD is indistinguishable from that of systemic RDD, this study emphasizes that purely cutaneous RDD is a distinct clinical entity in regard to its epidemiology and remains localized to the skin even with long-term follow-up. Patients with purely cutaneous RDD are of an older age at onset of disease (median = 43.5 years), with a reversed male/female ratio. There are no significant systemic extracutaneous or serologic manifestations. Whereas systemic RDD is commonly seen in blacks and only rarely reported in Orientals, the majority of the patients in this series with purely cutaneous RDD are Asians and whites.

"Basaloid carcinoma" of the uterine cervix is a neglected and underrecognized entity that is not included in the current World Health Organization's classification of cervical neoplasms. Historically, this term has been used synonymously with adenoid basal carcinoma (ABC). In recent years, however, it has become evident that a broad spectrum of basaloid cervical neoplasms exist. At one end of the spectrum are low-grade lesions, such as ABC; at the opposite end of the spectrum there are aggressive tumors, including adenoid cystic carcinoma, large cell neuroendocrine carcinoma, and basaloid squamous carcinoma. The purpose of this review is to revisit the concept of basaloid tumors of the cervix, to define their morphologic spectrum, and to address potential pitfalls in the differential diagnosis. To avoid confusion, use of the term "basaloid squamous cell carcinoma" is recommended when diagnosing a cervical tumor with histologic features of "basaloid carcinoma," as seen in other anatomic sites. A proposed classification of basaloid tumors of the uterine cervix is also presented.