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Biomedical subjects

K Hollowood

Publications and source records attributed to K Hollowood.

At least 19 recordsLinked to original sources

Melanomas in renal transplant recipients.

BACKGROUND: It is well documented that renal transplant recipients are at increased risk of developing skin cancers, in particular squamous cell carcinomas. Less extensively reviewed in the literature is the increased incidence of malignant melanoma. We have reviewed 10 patients in the Oxford renal transplant population who developed 12 melanomas following transplantation. OBJECTIVES: To determine the incidence and characteristics of melanoma in renal transplant recipients. METHODS: We reviewed the case notes and pathology of all patients who developed melanoma within the Oxford Renal Transplant Unit. The clinical details were recorded including date of transplant, immunosuppressive therapy, interval between transplant and melanoma, site of occurrence, history of sun exposure, type of clinician diagnosing the melanoma, history of other skin malignancies and outcome. From the histopathology we documented various prognostic factors. RESULTS: Ten patients developed 12 melanomas (one patient had three melanomas) from a population of 1874 transplanted patients. The total number of transplant years was 11 942.2. The incidence of melanoma in our population was 12 per 11 942.2 transplant years, which is approximately 8 times greater than the standardized rate for this region. We found that the mean interval between transplant and melanoma was approximately 11 years (median 8.5). A dermatologist was the diagnosing clinician in at least 67% of cases. Melanomas occurred on the trunk in the majority of cases (58%), followed by the upper limb (25%). All patients apart from one are alive with no recurrence of their melanoma. One patient died as a result of metastatic melanoma. The mean follow-up period following melanoma was 3.7 years. In all patients apart from the patient who died, the melanomas were < 1 mm Breslow thickness. That patient's melanoma was 4.5 mm thick. There was no precursor naevus in eight of the 12 melanomas. In two there was a precursor dysplastic naevus. In the cases in vertical growth phase the tumour-infiltrating lymphocyte response was absent in four cases and nonbrisk in one patient. CONCLUSIONS: In the Oxford transplant population studied melanomas occurred at approximately 8 times the rate in the general population. This is the highest rate reported in the literature. The patients had a better outcome than reported previously. This may be due to detection at a relatively early stage. Renal transplant recipients attend dedicated dermatology clinics in Oxford, which may have contributed to the early diagnosis and good outcome.

Adult↗

Late recurrence of dermatofibrosarcoma protuberans in the female breast: a case report.

The case presented is of a 39-year-old female who, at the age of 13 years, had had a "dermatofibroma" excised from her left breast. Twenty-six years later she developed an unsightly "stretched scar". Excision biopsy demonstrated a dermatofibrosarcoma protuberans (DFSP). This was managed by wide local excision, preservation of the nipple-areolar complex, and immediate reconstruction with a pedicled latissimus dorsi flap. Review of the original histology confirmed the presence of DFSP, revising the original diagnosis. Most DFSPs recur within 3 years of primary excision. Such prolonged latency prior to recurrence has not been previously described. This reinforces the need to educate patients regarding the importance of long-term scar surveillance following skin tumour excision.

Adult↗

p53-specific CD8+ T-cell responses in individuals with cutaneous squamous cell carcinoma.

BACKGROUND: Systemic immunosuppression is a significant risk factor for cutaneous squamous cell carcinoma (SCC). p53 is mutated and overexpressed in up to 90% of cutaneous SCC lesions. Despite considerable evidence that the immune response is important in the control of cutaneous SCC, there are no studies documenting potential tumour-associated antigens. OBJECTIVES: We tested the hypothesis that individuals with cutaneous SCC have functional circulating CD8+ T cells specific for p53. METHODS: Interferon-gamma immunosorbent assays were used to screen peripheral blood mononuclear cells for reactivity to six p53-derived HLA-A*0201-restricted epitopes from HLA-A*0201-positive patients and controls. RESULTS: We observed significantly elevated frequencies of p53-specific CD8+ T cells in seven of 26 individuals with cutaneous SCC and in one of 10 controls. The degree of lymphocytic infiltrate significantly correlated with the frequency of CD8+ T cells specific for p53 epitopes, but not with control epitopes. CONCLUSIONS: Overall, these data suggest that p53 may represent a target for CD8+ T cells in a proportion of individuals with cutaneous SCC.

CD8-Positive T-Lymphocytes↗

Multiple scrotal epidermolytic acanthomas; secondary to trauma?

Epidermolytic hyperkeratosis (EH) is an abnormality of epidermal maturation, most commonly due to mutations in keratins 1 and 10, which may be a congenital or an acquired defect. The term epidermolytic acanthoma was applied to a solitary discrete epidermal proliferation characterized by EH. Subsequently there have been several reports of disseminated epidermolytic acanthomas. We report a rare case of multiple epidermolytic acanthomas localized to the scrotum. With the aetiology of epidermolytic acanthoma unknown, trauma has been postulated as a possible cause. Our patient repetitively scratched his scrotum for 5 years and we believe that this action triggered his multiple scrotal epidermolytic acanthomas.

Acanthoma↗

Subungual melanoma with osteocartilaginous differentiation.

Osteocartilaginous metaplasia is known to occur rarely in melanomas, particularly in subungual melanomas. We present a case of a calcified subungual soft tissue tumour in which biopsy of the lesion showed malignant round and spindle-shaped tumour cells, many of which were associated with the formation of cartilage and osteoid-like material. Subsequent resection showed clear histological evidence of a subungual melanoma. Tumour cells expressed S100, melan-A and neurone-specific enolase but were negative for HMB45. Diagnostic radiological and histological features and the nature of the osteocartilaginous differentiation within this lesion is discussed.

Antigens, Neoplasm↗

Follicular lymphoma with marginal zone differentiation: cytogenetic findings in support of a high-risk variant of follicular lymphoma.

AIMS: The pathogenesis and clinical significance of marginal zone differentiation in follicular lymphoma remains to be determined, although genetic alterations are likely to be important determinants of both. We therefore report the cytogenetic findings in three cases of follicular lymphoma with marginal zone differentiation studied by routine karyotyping and in-situ hybridization. METHODS AND RESULTS: The morphology and immunophenotype of each case was typical of follicular lymphoma displaying marginal zone differentiation. Karyotyping, performed on GTL-banded preparations of cell cultures derived from fresh lymph node tissue, revealed a complex karyotype in all three cases, including t(14;18)(q32;q21) and abnormalities associated with progression and/or transformation of follicular lymphoma. In addition, trisomy 3 was found in one case and translocations between the q27-29 region of chromosome 3 and chromosome 2 in the other two cases; the latter was identified only in subclones derived from less complex stem lines possessing t(14;18). In-situ hybridization, performed on sections cut from routinely processed paraffin-embedded tissue blocks, localized cells possessing these abnormalities of chromosome 3 to both the follicular and marginal zone components of two lymphomas studied in this way. CONCLUSIONS: Trisomy 3 and alterations involving the q27-29 region of chromosome 3 are implicated in the pathogenesis of de novo marginal zone lymphoma. Their presence in the current cases indicates that they may also be responsible for marginal zone differentiation in follicular lymphoma when cells harbouring these genetic alterations are exposed to the appropriate microenvironment. Our findings are consistent with follicular lymphoma with marginal zone differentiation as a high-risk variant of follicular lymphoma.

Aged↗

Expression of sarco/endo-plasmic reticulum Ca2+-ATPase type 2 isoforms (SERCA2) in normal human skin and mucosa, and Darier's disease skin.

BACKGROUND: The recent report that mutations in ATP2A2, which encodes the Ca2+ transporting sarco/endo-plasmic reticulum pump type 2 isoforms (SERCA2), cause Darier's disease (DD) suggests that SERCA2 plays an important role in epidermal cell adhesion and differentiation. However, no data exist regarding SERCA2 expression in normal human skin, mucosa and DD. OBJECTIVES: We have therefore investigated SERCA2 expression in normal human skin (40 samples), oral and vaginal mucosa (13 samples) and DD lesional skin (six samples). MATERIALS AND METHODS: These investigations were performed with a mouse monoclonal antibody specific for human SERCA2, using a standard ABC immunoperoxidase technique. RESULTS: SERCA2 was expressed in all specimens. SERCA2 expression was pronounced in the subnuclear aspect of basal epidermal keratinocytes, with variable suprabasal expression. SERCA2 expression was also observed in the infundibulum and outer root sheath of hair follicles; germinative and mature cells of sebaceous glands; secretory coil and duct of eccrine glands; apocrine gland cells, and arrector pili muscle. Fibroblasts and blood vessels (endothelium and muscle) expressed SERCA2, whereas nerves did not. SERCA2 expression was observed throughout oral and vaginal mucosa. In DD skin, strong SERCA2 positivity was detected in the basal, suprabasal and acantholytic lesional cells. Perilesional DD skin was comparable to normal skin. CONCLUSIONS: These findings support the hypothesis that SERCA2 is an important player in cutaneous biology, and provide baseline data that will facilitate the design and interpretation of functional studies of cutaneous SERCA2.

Calcium-Transporting ATPases↗

Keratosis pilaris atrophicans in mother and daughter.

We report two cases of keratosis follicularis spinulosa decalvans in a Caucasian family involving a 28-year-old woman and her mother. This is an unusual family in that no male relatives are similarly affected. Secondly, both patients have no significant eye changes but quite extensive scarring alopecia. To the best of our knowledge this is the second reported family in the UK.

Adult↗

S100 expression in cutaneous scars: a potential diagnostic pitfall in the diagnosis of desmoplastic melanoma.

AIMS: The histological distinction of desmoplastic melanoma from cutaneous scar tissue, particularly in the context of re-excision specimens or possible recurrence, may be very difficult. Immunostaining for S100 protein is often used to discriminate although there are little data on S100 expression in scar tissue. The aim of this study was to assess whether S100-positive cells are present in dermal scars and, if so, their extent, distribution and nature. METHODS AND RESULTS: Twenty-two re-excision specimens of previously biopsied nonmelanocytic skin lesions were reviewed. Formalin-fixed paraffin-embedded sections containing dermal scars were stained by a standard ABC immunoperoxidase technique for S100 protein, CD1a and neurofilaments. The distribution and morphology of positive cells within the dermal scar tissue were documented. Cells expressing S100 protein were identified within the scars of 21 of the 22 cases. The number of S100-positive cells varied between cases but in four specimens was substantial. They displayed a variety of morphological appearances but the majority were spindle-shaped. A few showed mild cytological atypia. It is suggested that the majority represent Schwann cells with a minority of Langerhans cells and cells of uncertain lineage. CONCLUSION: S100-positive cells, including spindle cells showing mild atypia, are found in cutaneous scars. S100 staining of re-excision specimens or putative recurrences of desmoplastic melanoma should be interpreted with caution.

Antigens, CD1↗

Extraneural perineurioma of the face: an unusual cutaneous presentation of an uncommon tumour.

Perineurioma is an uncommon, benign tumour of the peripheral nerve sheath that has two major clinicopathological forms -- intraneural and extraneural. We present a case of extraneural perineurioma that occurred at an unusual site -- the facial skin of a 70-year-old woman -- which illustrates the wide, and potentially misleading, clinicopathological spectrum of this poorly recognized tumour.

Aged↗

Borrelia burgdorferi-associated cutaneous marginal zone lymphoma: a clinicopathological study of two cases illustrating the temporal progression of B. burgdorferi-associated B-cell proliferation in the skin.

AIMS: A relationship between Borrelia burgdorferi and primary cutaneous B-cell lymphoma (PCBCL) has recently been confirmed following demonstration of the organism in lesional skin of patients with PCBCL. We report herein two cases of B. burgdorferi-associated PCBCL which strengthen this association by demonstrating the organism in cutaneous B-cell infiltrates present at sites in which PCBCL subsequently developed. METHODS AND RESULTS: All studies were performed on formalin-fixed paraffin-embedded tissues. These were examined by routine light microscopy and immunohistochemically by a standard streptavidin-biotin-complex technique. Genotypic studies were also undertaken using semi-nested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement, and nested PCR for B. burgdorferi flagellin gene. Both patients presented with erythematous skin lesions, biopsy of which showed dense perivascular infiltrates comprising small T-lymphocytes and collections of B-blasts. Primary cutaneous marginal zone lymphoma (MZL) developed subsequently in both cases at the same site. PCR for B. burgdorferi flagellin gene was positive in the perivascular lymphocytic infiltrates and the succeeding lymphomas in both patients. CONCLUSIONS: These results show that, at least in some instances, PCBCL arises from chronically stimulated lymphoid tissue acquired in the skin in response to B. burgdorferi infection. This may have significant therapeutic implications and warrant further studies on the extent of this association.

Adult↗

Primary cutaneous B-cell lymphoma and Borrelia burgdorferi infection in patients from the Highlands of Scotland.

Although a link between primary cutaneous B-cell lymphoma (PCBCL) and Borrelia burgdorferi infection has long been suspected, previous studies have not demonstrated a significant association. The authors looked for evidence of B. burgdorferi in 20 cases of PCBCL from the Scottish Highlands, an area with endemic Lyme disease, and compared their findings with those in 40 control patients (20 undergoing wide reexcision at sites of malignant melanoma and 20 biopsies of inflammatory dermatoses). All studies were performed on formalin-fixed, paraffin-embedded tissues. The cases of PCBCL were classified according to criteria described by the European Organization for Research and Treatment of Cancer Cutaneous Lymphoma Project Group using a combination of morphology, immunohistochemistry, and seminested polymerase chain reaction (PCR) for immunoglobulin heavy chain gene rearrangement. A nested PCR was performed on deoxyribonucleic acid (DNA) extracts from the lymphoma and control cases using primers to a unique conserved region of the B. burgdorferi flagellin gene. B. burgdorferi-specific DNA was detected in seven of 20 lymphoma cases (five of 12 marginal zone lymphomas, one of five primary cutaneous follicle center cell lymphomas, one of three diffuse, large B-cell lymphomas of the leg) and in one melanoma reexcision patient of 40 control subjects. The relationship between B. burgdorferi and PCBCL was significant when compared with the control groups separately (p <0.05) or in combination (p <0.01). These results provide strong evidence to support the concept of B. burgdorferi-driven lymphomagenesis in the skin.

Adult↗

Primary juxtaarticular soft tissue lymphoma arising in the vicinity of inflamed joints in patients with rheumatoid arthritis.

AIMS: Primary soft tissue lymphoma is uncommon and little is known regarding its aetiology and pathogenesis. In a review of 37 soft tissue lymphomas we uncovered three cases associated with rheumatoid arthritis which we report herein. METHODS AND RESULTS: The clinical records and pathology of the cases are described together with the results of in situ hybridization studies with oligonucleotide probes to Epstein-Barr virus (EBV) encoded RNA (EBER). All three patients were females with a long-standing history of rheumatoid arthritis ranging from 9 to 17 years. Each presented with a soft tissue mass in the vicinity of a joint affected by rheumatoid disease. All had received prior treatment with nonsteroidal anti-inflammatory drugs and one also received gold, penicillamine and intra-articular steroids to affected joints. None had received methotrexate. Histologically, the juxtaarticular soft tissue masses were all B-cell lymphomas. None were associated with EBV as determined by in situ hybridization. CONCLUSIONS: These cases document an association between rheumatoid arthritis and soft tissue lymphoma of B-cell type, arising in the vicinity of an affected joint. Chronic local immune stimulation may have played a significant role in the genesis of these lymphomas, unlike the frequently reversible and EBV-positive lymphomas that occur in rheumatoid patients on immunosuppressive therapy.

Adult↗