Jaroslaw Jedrych

Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases

Desmoplastic trichoepithelioma (DTE) is a benign follicular tumor occurring most commonly within facial skin of young and middle‐aged women, morphologically characterized by a superficial dermal proliferation of basaloid cells growing in narrow strands embedded in a desmoplastic stroma associated with small keratinizing cysts. DTE must be distinguished from other benign epithelial proliferations such as syringoma, microcystic adnexal carcinoma and infiltrating basal cell carcinoma. Among morphological features useful in that distinction, perineural involvement is considered a feature indicative of malignancy. We present a series of seven DTEs with otherwise typical presentation and morphology, nevertheless showing epithelium present in the perineural spaces of adjacent small dermal nerves. Patients ranged in age from 14 to 66 years (mean 44 years). All seven tumors were restricted to dermis, showed strands of basaloid epithelium in desmoplastic stroma and contained CK20‐positive cells. Additionally, five of five examined tumors displayed diffuse expression of p75 neurotrophin receptor. Five patients were followed up clinically (follow‐up time range: 2 months–4 years). No tumor recurrence was observed in any of these patients. We postulate that perineural involvement is an unusual feature of DTE that should not be equated with malignancy or lead to unnecessary over‐treatment.

Expression of p75 neurotrophin receptor in desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma.

Abstract:The histological discrimination between desmoplastic trichoepithelioma, infiltrative basal cell carcinoma, and microcystic adnexal carcinoma encountered in small biopsies is challenging when only morphological criteria are applied. The objective of this study is to test the use of p75 neurotrophin receptor (p75NTR) as an adjunct aid in classification of these tumors. Immunohistochemistry for p75NTR antigen was performed on routinely processed biopsies of 37 desmoplastic trichoepitheliomas, 11 infiltrative basal cell carcinomas, and 9 microcystic adnexal carcinomas diagnosed by morphological criteria in conjunction with results of CK20 immunostains. Cases were analyzed for the extent and intensity of p75NTR expression. Diffuse immunoreactivity was defined as involving >90% of tumor cells. Of the 37 desmoplastic trichoepitheliomas, 35 (94%) displayed strong diffuse immunoreactivity of tumor cells, proving high sensitivity of the marker to detect this tumor. However, despite the fact that diffuse p75NTR expression reached statistical significance in differentiating desmoplastic trichoepithelioma from infiltrative basal cell carcinoma (Fisher exact test P < 0.0001) and microcystic adnexal carcinoma (P < 0.0016), specificity of the stain is unsatisfactory because strong diffuse expression of p75NTR by neoplastic cells was observed in 4 (36%) cases of infiltrative basal cell carcinomas and 4 (44%) cases of microcystic adnexal carcinoma. This study demonstrates a significant difference in p75NTR expression in selected sclerosing neoplasms of the skin. Nevertheless, the practical value of p75NTR as an adjunct marker in the differential diagnosis of these tumors seems to be limited because of significant overlap in amount of p75NTR immunoreactivity.

Primary carcinoid tumor of the skin: a literature review.

Primary carcinoid tumor of the skin (PCTS) is an uncommon indolent neoplasm, with 10 cases described in the literature. The tumors affect patients in the sixth to ninth decades of life (mean = 66.3 years) with an equal gender distribution and predilection for the head and trunk. They present as slowly enlarging nodules of variable duration, ranging from 1 to 60 years (mean = 11.4 years). PCTS is characterized by architectural, cytomorphologic, ultrastructural, and immunohistochemical features typical of a low-grade neoplasm with neuroendocrine differentiation. PCTS typically follows a benign clinical course and therefore has to be distinguished from cutaneous metastases of visceral carcinoid tumors, which herald dissemination of malignancy and poor prognosis. While the distinction from other histologically similar entities can be achieved by histopathological examination, PCTS can be distinguished from a visceral metastasis only by a judicious clinicopathologic correlation. Herein we describe the clinical presentation, histological appearance, and management of these tumors.

Dysplastic nevi with severe atypia: Long-term outcomes in patients with and without re-excision

Background: Dysplastic nevi with severe atypia (severely dysplastic nevi [SDN]) are frequently re‐excised because of the concern that these lesions may in fact represent early melanoma. Data on long‐term follow‐up of these patients are limited. Objective: We sought to determine the rate of subsequent melanoma development in patients with SDN who underwent re‐excision versus those who did not and to determine factors associated with decision to re‐excise. Methods: A retrospective single institutional study was conducted with 451 adult patients (mean age 41.3 years) with SDN biopsied between November 1994 and November 2004, with clinical follow‐up of at least 5 years. Results: In 451 patients with SDN, re‐excision was performed on 36.6%. Two melanomas were diagnosed in the re‐excision specimens. Subsequent metastatic melanoma developed in 7 patients, all of whom had a history of melanoma. Margin comments influenced decision to re‐excise. Limitations: This was a retrospective study at a single institution. Conclusion: Re‐excision of all SDN may not be necessary.

Primary cutaneous endocrine mucin-producing sweat gland carcinoma co-occurring simultaneously with low-grade ductal mucinous breast cancer: a clinicopathologic conundrum.

To the Editor: Endocrine mucin–producing sweat gland carcinoma (EMPSGC) is a rare, underreported, low-grade cutaneous malignancy affecting elderly patients with a median age of 70 years, and a significant predilection for females. The tumor typically occurs on the eyelids or periorbital skin and manifests clinically as a nondescript slowly enlarging flesh-colored nodule, plaque, or swelling. Histologically, it is characterized by low-grade morphological features, production of mucin, and expression of neuroendocrine markers. The tumor is clinically indolent and cured by local excision; however, local recurrences may occur. The coexistence of EMPSGC and low-grade ductal mucinous breast carcinoma has not been hitherto reported. A 75-year-old white female with no oncologic history presented to her dermatologist with a small, asymptomatic, nonulcerated, skin-colored nodule located on the skin adjacent to her left lower eyelid, and slowly enlarging over a period of approximately 3 years. The initial pathologic interpretation at an outside institution was of poorly differentiated carcinoma, and a metastasis was favored. The patient requested a second opinion. Our microscopic examination of the excisional biopsy revealed a well-demarcated dermal tumor composed of solid and focal cribriform nests and strands separated by thin fibrous septa. The nests consisted of medium sized round to oval cells with relatively monomorphic nuclei and amphophilic cytoplasm embedded in a mucinous stroma (Figs. 1A–C). Occasional intracellular mucin and hyalinized fibrovascular cores were noted. The tumor cells were positive for cytokeratin AE1/AE3, estrogen and progesterone receptors, GCDFP15, cytokeratin 7, and patchy for synaptophysin (Figs. 1E, F), whereas negative for cytokeratin 20, CDX-2, and S100. There was no immunohistochemical evidence of Her2/neu overexpression. Ki-67 proliferation index ranged from 5% to 10%. P63 and calponin revealed a layer of myoepithelial cells at the periphery of some tumor nests, indicating an in situ component (Fig. 1D). Based on morphological and immunohistochemical features, the tumor was reclassified as a primary cutaneous EMPSGC. Although a primary cutaneous malignancy was favored, given the demographics of the patient, screening for breast cancer was suggested. Subsequent imaging showed a left breast mass that was biopsied and excised to reveal a 2.8 cm welldifferentiated invasive ductal mucinous carcinoma (Nottingham grade 1) with a focal in situ component (Figs 2A–C). The tumor showed a diffuse expression of estrogen and progesterone receptors,

Another infant with an extracephalic hair follicle nevus: an under‐diagnosed entity?

To the Editor , We have recently reported an extracephalic occurrence of a congenital hair follicle nevus detected in a healthy 6-month-old male infant.1 Shortly thereafter, we encountered another 7-month-old girl evaluated for a small, firm, skin-tag-like lesion noted at birth on her abdomen (Fig. 1). Physical examination showed a similar 0.6× 0.4 cm asymptomatic, exophytic, pedunuculated, skin-colored cutaneous nodule located in the proximity of the mid-line in the epigastric area. The growth was freely movable and stable in size and appearance since her birth. The patient was otherwise healthy with no known prenatal or developmental abnormalities or significant family history. The growth was snip-biopsied in toto and submitted for histopathologic examination. Microscopic examination demonstrated an exophytic proliferation composed of an aggregation of distorted vellus hair follicles accompanied by scattered sebaceous and eccrine glands, and occasional smooth muscle fibers (Fig. 2). The lesional stroma was fibrotic with increased density around the hair follicles. The adnexal elements were distributed in a disorganized fashion underlining the hamartomatous nature of the lesion. No adipose tissue, cartilage or follicular cystic dilatations were seen on the initial and deeper sections. Hair follicle nevus is a rare hamartoma typically occurring on the face as a clinically non-descript papule, plaque or nodule.2 Multiple tumors in the same patient have been reported, sporadically following the Blaschko lines.3 Hair follicle nevus presents either at birth Fig. 1. Hair follicle nevus. A) The polyp is located on the epigastric area in close proximity to the mid-line. B) Clinically, it is a skin-colored polypoid nodule.

Comparison of PCR-based detection of chromogranin A mRNA with traditional histological lymph node staging of small intestinal neuroendocrine neoplasia

BackgroundAccurate neuroendocrine neoplasia (NEN) staging is vital for determining prognosis and therapeutic strategy. The great majority of NENs express chromogranin A (CgA) which can be detected at a protein or transcript level. The current standards for lymph node metastasis detection are histological examination after Hematoxylin and Eosin (H&E) and CgA immunohistochemical (IHC) staining. We hypothesized that detection of CgA mRNA transcripts would be a more sensitive method of detecting these metastases.FindingsWe compared these traditional methods with PCR for CgA mRNA extracted from formalin fixed paraffin embedded slides of lymph nodes (n = 196) from small intestinal NENs, other gastrointestinal cancers and benign gastrointestinal disease. CgA PCR detected significantly more NEN lymph nodes (75%) than H&E (53%) or CgA IHC (57%) (p = 0.02). PCR detected CgA mRNA in 50% (14 of the 28) of SI-NEN lymph nodes previously considered negative. The false positive rate for detection of CgA mRNA was 19% in non-neuroendocrine cancers, and appeared to be due to occult neuroendocrine differentiation or contamination by normal epithelium during histological processing.ConclusionsMolecular pathological analysis demonstrates the limitations of observer-dependent histopathology. CgA PCR analysis detected the presence of CgA transcripts in lymph nodes without histological evidence of tumor metastasis. Molecular node positivity (stage molN1) of SI-NEN lymph nodes could confer greater staging accuracy and facilitate early and accurate therapeutic intervention. This technique warrants investigation using clinically annotated tumor samples with follow-up data.

Multiple cutaneous metastases: a rare and late sequelae of lacrimal gland adenoid cystic carcinoma

Primary cutaneous adenoid cystic carcinoma (ACC) is an uncommon malignancy with approximately 60 cases reported in the literature. Metastatic ACC to the skin is even less frequent with eight previously published cases, including only one arising from the lacrimal gland. We report a case of a 61‐year‐old male, who developed multiple cutaneous metastases to the scalp and back from a lacrimal gland ACC 21 years after the initial diagnosis. Initially, in the absence of the past clinical history, the cutaneous lesions were interpreted as primary ACC of the skin. Histopathologically, the metastatic lesions were poorly circumscribed dermal and subcutaneous nodules that were composed of islands of basaloid epithelial cells with ducts and cribriform pattern, mucinous stroma and prominent perineural invasion. Histomorphologically, the cutaneous tumors were similar to the primary ACC. The cutaneous metastases were preceded by tumor dissemination to the lung and other visceral organs, and ultimately led to patients demise. This report illustrates the importance of juditious clinico‐pathologic correlation and raises awareness regarding prolonged latency of cutaneous metastases in patients with visceral ACC.

Cutaneous squamous cell carcinoma with epidermodysplasia verruciformis-like features in a patient with Schimke immune-osseous dysplasia

Schimke immune-osseous dysplasia1 (SIOD) is an autosomal recessive disorder caused by mutations in the SMARCAL1 gene encoding an ATP-driven annealing helicase that stabilizes stalled replication forks and facilitates DNA repair during replication2 . The syndrome is characterized by spondyloepiphyseal dysplasia, steroid-resistant nephropathy and cellular immune deficiency.

Aneurysmal fibrous histiocytomas with recurrent rearrangement of the PRKCD gene and LAMTOR1-PRKCD fusions

Aneurysmal fibrous histiocytoma (FH) is an uncommon variant of cutaneous benign fibrous histiocytoma/dermatofibroma1 typically presenting as a solitary, pigmented, up to several centimeters in size nodule on extremities or trunk of middle-aged adults.1,2 Some cases may be clinically concerning for melanoma or vascular neoplasia.1 The local recurrence rate is ~20%, if incompletely excised.1 This article is protected by copyright. All rights reserved.