Langerhans cell sarcoma with lineage infidelity/plasticity: a diagnostic challenge and insight into the pathobiology of the disease.

Langerhans cell sarcoma is a very rare and aggressive tumor of Langerhans cell lineage, for which aberrant expression of T-cell-related antigens has not yet been reported in a primary skin tumor. The authors describe the first known case of a primary cutaneous Langerhans cell sarcoma with lineage infidelity and use comparative genomic hybridization to investigate the genetic composition of the tumor and detect DNA copy number alterations throughout its entire genome. The case involves a 62-year-old woman who presented with an irregular nodule on the forehead surrounded by smaller lesions in its vicinity. The clinical impression was melanoma with satellitosis. The biopsy specimen showed an epidermotropic tumor with moderate-to-marked cellular pleomorphism and significantly increased mitotic rate but no necrosis. The immunoprofile of the lesion was remarkable, as next to common Langerhans cell markers: Langerin, CD1a, S100, and CD4; it also exhibited an aberrant T-cell phenotype with the expression of CD2, CD3, and CD43. In addition, fascin and CD30 were also expressed, further exaggerating potential diagnostic pitfalls. Langerhans cell lineage was confirmed by the demonstration of characteristic Birbeck granules on electron microscopy. Whole genome analysis for copy number changes and loss of heterozygosity showed a complex karyotype with variable hyperdiploidy and numerous allelic imbalances. Significant findings included a homozygous deletion at 9p21 involving the CDKN2A and loss of heterozygosity at 17p involving TP53 gene, coupled with a TP53 missense mutation. Despite reexcision and multiagent systemic chemotherapy, the patient died of metastasis 2 years after diagnosis. This case is an outstanding example of lineage infidelity in a hematologic malignancy and the utilization of comparative genomic hybridization in characterizing its genetic abnormalities.

Mullerianosis of inguinal lymph nodes: report of a case.

We report a case of florid mullerianosis involving inguinal lymph nodes, a simulator of metastatic adenocarcinoma. The patient was a 48-year-old woman with symptomatic leiomyomas and enlarged right inguinal lymph nodes. Microscopically two lymph nodes were partially or completely replaced by cystically dilated and small glands, many of which contained mucin. The larger of the two lymph nodes was completely replaced by cystically dilated structures and long branching tubular glands that focally displayed well-defined lobular and papillary patterns. The glands were lined predominantly by a single layer of columnar cells similar to those of the endocervical epithelium. The columnar cells had bland basal nuclei and abundant mucin-containing cytoplasm. Admixed with these cells were others similar to those of tubal epithelium. Some of the glands were partially surrounded by a cellular ovarian-like stroma. There was focal cytologic atypia but no mitotic figures were seen. There was also focal oxyphil cell metaplasia with atypical hobnail cells. Some cystically dilated glands that contained abundant mucin were lined by flat epithelial cells. Because of gland rupture, mucin extravasated into the stroma but did not elicit a desmoplastic response. Surgical pathologists should be aware of mullerianosis in lymph nodes to avoid confusing it with metastatic adenocarcinoma.

Rhabdomyosarcoma arising in a congenital melanocytic nevus.

A variety of malignancies have been reported to arise within congenital melanocytic nevi, most commonly malignant melanoma, but rarely rhabdomyosarcoma, liposarcoma, and malignant peripheral nerve sheath tumor as well. There have been only three documented cases of rhabdomyosarcoma arising within congenital melanocytic nevi: two embryonal rhabdomyosarcomas and one mixed liposarcoma and rhabdomyosarcoma. One of these cases was also associated with neurocutaneous melanosis. We report a fourth case of rhabdomyosarcoma originating from a congenital melanocytic nevus. A 4-year-old girl presented with a large ulcerated nodule that developed within a hairy congenital nevus on her left gluteal and sacral regions. Her parents refused postoperative adjuvant therapy, and she died 13 months after surgical excision. Histologic sections showed a lesion with two distinct components. There was an expansile proliferation of pleomorphic cells within a fibromyxoid stroma. The neoplastic cells were spindled, and some had abundant eosinophilic globular cytoplasm with occasional cross-striations characteristic of rhabdomyoblasts. They strongly expressed desmin and myoglobin and were negative for S-100 protein and HMB-45. The tumor merged with an adjacent congenital melanocytic nevus characterized by a proliferation of uniform nonatypical melanocytes. The finding of both rhabdomyoblastic and melanocytic differentiation within the same lesion lends support to the hypothesis of their derivation from common pluripotential stem cells or neural crest cells.