Ben Tallon

Permanent chemotherapy-induced alopecia: Case report and review of the literature

Reversible alopecia following chemotherapy is well recognized and typically not evaluated by dermatologists. However, there are an increasing number of reports of permanent chemotherapy-induced alopecia, typically following high-dose chemotherapy and subsequent bone marrow transplantation. We describe an unusual case of permanent alopecia in a patient who received adjuvant chemotherapy for breast carcinoma, and not a conditioning regimen before bone marrow transplantation. A unique histologic finding of replacement of anagen hair follicles by linear columns of basaloid epithelium is reported. We review the clinical and histologic findings of permanent chemotherapy-induced alopecia and speculate on its pathogenesis.

Where pigmented pilomatricoma and melanocytic matricoma collide.

Pilomatricoma and matricoma are 2 benign epithelial tumours derived from the hair matrix. Although containing the same constituent cells, the silhouette differs, with matricoma comprised of a predominantly solid basaloid proliferation with only focal areas of shadow cell formation. The recently described melanocytic matricoma appears to be a similar tumor with numerous interspersed melanocytes. We studied retrospectively 28 pilomatricomas and 2 pilomatrical carcinomas to check for the presence of melanocytes using immunohistochemical staining to S-100 and Melan-A. Three cases of pilomatricoma with prominent melanocytic hyperplasia were detected, confirming this as a rare (11%) occurrence. Both cases of pilomatrical carcinoma were negative. Comparison of these tumors with a further case of melanocytic matricoma led to a critical analysis of the relationship of pilomatricoma, matricoma, and melanocytic matricoma. Although further comparison is required, we suggest that melanocytic matricoma may be simply a pigmented melanocytic variant of matricoma, in the same way as we accept pigmented pilomatricoma as a variant of pilomatricoma. In this report we provide features that may be used to discriminate matricoma and pilomatricoma and their pigmented variants.

FoxP3 expression is increased in cutaneous squamous cell carcinoma with perineural invasion

To the Editor, Forkhead box P3 (FoxP3) belongs to a family of transcriptional regulatory proteins, and is a marker for a specific subset of T lymphocytes. These FoxP3 (CD4+/CD25+) T lymphocytes are regulatory T cells that have been shown to be overexpressed and associated with recurrence or poor prognosis in a number of malignancies including melanoma.1 Squamous cell carcinoma (SCC) is the second most common skin cancer, with the potential to cause significant morbidity both from the disease and its treatment. Accurate determination of prognostic indicators such as perineural invasion (PNI) is essential to tailor treatment options such as local radiation therapy.2 Therefore, attention to additional prognostic indicators may aid in patient management decisions. We retrospectively performed FoxP3 staining in cases of SCC and have shown increased expression in cases with PNI. From the files of the Skin Pathology Laboratory in the Boston University Department of Dermatology, we retrieved 30 SCCs with and 30 SCCs without documented PNI. All cases were biopsies taken of well-differentiated SCC. Control matching by the depth and size of the lesion was not possible given that the majority of the lesions were transected at the margins. No lymphovascular invasion was present. PNI was defined as evidence of atypical squamous epithelium invading the perineurium. Briefly, formalin-fixed paraffin-embedded specimens were cut into 5-μm thick sections, dewaxed in Xylene and hydrated with graded alcohols. Sequential alkaline phosphatase double staining was performed as previously described.3 Immunoperoxidase staining was performed with monoclonal antibody FoxP3 (236A/E7 1:100, Abcam, Cambridge, MA, USA) and CD3 (2GV6 0.45 μg/ml, Ventana Medical Systems, Inc, Tucson, AZ, USA). Positive controls were established from stock tissue sections of a lymphoid proliferation, and negative controls prepared by omission of the primary antibodies. Stained slides were examined for the areas of heaviest inflammatory infiltrate, where three representative photomicrographs were taken through a high power (40×) lens (Fig. 1). The staining reaction was recorded as a percentage of FoxP3 to CD3 positive cells and the mean of the three counts was compared. Cell counting was performed with the software program IPLab for windows (Scanlytics, Inc, Fairfax, VA, USA) (Fig. 1). Statistical analysis was performed using Graph Pad Software, Inc (La Jolla, CA, USA). Level of significance was determined with an unpaired t-test. This study was reviewed and approved by the Boston University Medical Center Institutional Review Board. Immunohistochemical staining revealed an increase in FoxP3 expression in the SCCs with PNI. Mean FoxP3/CD3 expression was 0.3653 and 0.5240 in the SCCs without and with PNI respectively (p < 0.0001). FoxP3 (CD4+ CD25+) regulatory T cells represent 5–10% of human CD4+ lymphocytes, and play an important function in tumor immunity.4 It has been shown that regulatory T cells can impair the lymphocytic response against melanoma.4 Our results have shown that there is increased FoxP3 expression in the tumor infiltrating lymphocytes of SCC. This corresponds to an increased proportion of regulatory T cells in SCC with PNI. Given the increased risk for local recurrence, leptomeningeal spread and death in SCCs with PNI,5 increased tissue FoxP3 expression may be associated with poor prognosis. This result is in keeping with a previous report showing an association between head and neck SCC with early recurrence and overexpression of regulatory T cells in the peripheral blood.6 Recently, no difference was detected in the proportion of

MITF positivity in atypical fibroxanthoma: a diagnostic pitfall.

Abstract:Microphthalmia transcription factor (MITF) is an established melanocytic marker originally credited with a high degree of specificity. We report a series of 11 atypical fibroxanthoma (AFX) from 2 laboratories showing positive MITF staining. Although there are multiple case reports illustrating MITF staining in a range of tumors, aberrant staining in AFX has not been previously reported. Awareness of the possibility of MITF positivity in AFX is important to avoid a misdiagnosis of melanoma. We also report positive MITF staining in 2 nonneural granular cell tumors and discuss the overlap with the granular subtype of AFX.

Porokeratosis ptychotropica: a rare and evolving variant of porokeratosis.

Porokeratosis ptychotropica represents a rare and under‐recognized variant of porokeratosis. There are also alternative descriptions for this disorder in the literature. Since its original description in 1995, additional characteristic features have been showed in case reports published in the literature. These cumulative reports, although still limited in numbers, have helped to further shape and define this entity. A case report and review of published literature on this unusual entity are presented. The specific combination of clinical, morphological and histopathological characteristics that can facilitate recognition of the disorder is discussed. There has been a call for uniformity in terminology and a suggestion for alternative terminology has been made. However, we discuss why the earlier term, porokeratosis ptychotropica, is still preferred.

Primary rhabdoid melanoma with clonal recurrence.

Melanoma with rhabdoid features is an uncommon melanoma variant. Many questions remain regarding rhabdoid differentiation and whether this phenotype represents a common pathogenetic pathway from distinct tissue malignancies. We describe a case of primary melanoma illustrating rhabdoid features, a recurrent rhabdoid clone and its diagnostic challenges. Immunohistochemistry in this tumor frequently involves loss of melanoma specific markers, while Vimentin may display a paranuclear accentuation in keeping with reported ultrastructural features. This case documents rhabdoid differentiation within a primary tumor and recurrence of the presumed more aggressive rhabdoid clone.

Pigmented Porokeratosis. A Further Variant

Abstract:Porokeratosis is a clonal disorder of keratinization characterized by the presence of the cornoid lamella. A number of variants of porokeratosis have been described, based on the clinical features and histologic features of the lesions. The authors present a case of porokeratosis with prominent melanocytic hyperplasia, which was biopsied to clinically exclude melanoma. The authors retrospectively studied cases of porokeratosis to look for the presence of melanocytic hyperplasia. Melanocytic hyperplasia was identified in 8 of 31 cases (25.8%). All of the cases except the index case were clinically nonpigmented but arose in solar damaged skin. This case represents a distinct variant of porokeratosis, and the authors propose the designation pigmented porokeratosis. Melanocytic hyperplasia is a benign condition, and it is important that this is not histologically confused with melanoma in situ, particularly in a context of clinically pigmented lesion. Increased recognition of pigmented porokeratosis is essential to avoid an erroneous diagnosis of melanoma in situ.

Assessment of tumor mitotic rate in primary cutaneous malignant melanomas 1 mm or less in thickness

BACKGROUND Tumor mitotic rate in thin melanomas is recognized as a powerful, independent prognostic factor predicting survival. In nonulcerated cases, the presence of any dermal mitotic activity upstages the disease to pT1b. The extent to which tissue should be histologically examined to assess mitogenicity, however, has not been studied. OBJECTIVE We sought to determine whether in staging thin melanomas, there is a significant benefit in examining numerous tissue sections containing invasive disease. METHOD In all, 71 cases of thin cutaneous melanomas diagnosed between January 2012 and June 2013 were identified after a search performed on the Pathlab database. The slides were retrieved and reviewed retrospectively, comparing the identification of the first dermal tumor mitotic figure, if present, at 4 check-points: the first, third, fifth, or tenth tissue section examined. RESULTS A statistically significant difference in identification of the first dermal mitotic figure was found in examining 1 versus 3 tissue sections (P = .0411). No significant difference was found in examining numerous tissue sections. LIMITATIONS This was a retrospective study from a single institution with a limited number of participants. CONCLUSION In staging thin melanomas without ulceration, the optimal number of sections to assess is 3. No additional benefit is gained by examining numerous tissue sections.

Pseudolymphomatous tumid lupus erythematosus of the oral mucosa.

Oral lesions are frequent complications of systemic lupus erythematosus, but only ulceration is included in the 1982 American College of Rheumatology revised criteria. Because the lack of a uniform classification, a range of ulcerative and keratotic lesions are typically described. In this report we describe a unique progressive irregularly cobblestoned and vegetating plaque of the oral mucosa with clinical and histological features mimicking a cutaneous lymphoma. Despite the papillomatous and extensive nature of the lesions and the dense lymphoid infiltrate with follicle formation suggesting a malignant lymphoproliferative process, the slow progression coupled with a mixed cell infiltrate and polyclonality supported a diagnosis of pseudolymphoma. Recognition of this entity is important to prevent diagnosing them as a malignant lymphoma. As well as with the other mucosal lesions in lupus erythematosus, this pseudolymphomatous variant should be added to the disease spectrum.

MITF Positivity in Atypical Fibroxanthoma.

trunk, extremities, and genitalia. The histopathologic and ultrastructural features are indistinguishable from those of hereditary epidermolytic hyperkeratosis (EHK). The underlying genetic derangement in EHK is mutations in KRT 1 and 10 genes. It has been suggested that genital EA may be a local variant of generalized EHK. Previous studies failed to provide molecular evidence of human papillomavirus infection in these lesions, which may simulate condylomas clinically. There were no studies of KRT gene mutations in EA limited to the genitalia. We studied a 47-year-old woman who presented with several asymptomatic whitish or skin colored papules in the genitalia (Fig. 1). The histopathology showed marked acanthosis and EHK in the spinous and granular cell layers (Figs. 2 and 3). In situ hybridization for pan human papillomavirus DNA was negative. Germline DNA and DNA extracted from a fresh biopsy of an EA lesion were also studied for KRT1 and KRT10 gene mutations as previously described. No mutations were found. In summary, our case did not prove to be a local variant of generalized EHK or the consequence of an acquired mutation in KRT1 or KRT10. Other factors are probably responsible for the EHK changes in these lesions. Ella Egozi-Reinman, MD*† Emily Avitan-Hersh, MD*† Aviv Barzilai, MD‡ Margarita Indelman, MSc*† Reuven Bergman, MD*† *Department of Dermatology, Rambam Health Care Campus and the Ruth and Bruce Rappaport †Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel ‡Department of Dermatology, Sheba Medical Center, Tel Aviv, Israel