Case 9 -

Malignant Melanoma, Spindle Cell Type Paul E. Wakely, Jr.

Clinical History A 47 y/o man complained of a lump in his neck which has been present for about 2 weeks. Physical examination reveals a 2 x 3 cm. firm left upper cervical lymph node. Cytopathology: Case 9 - Figure 1 - Case 9 - Figure 2 - Case 9 - Figure 3 - dispersed single cell architecture with some loose cell groupings large cells with most having oval or elongated nuclei, small or indistinct nucleoli, and unipolar or bipolar tapered cytoplasmic processes some cells with mirror image nuclei; No LGBs, background stroma, or necrosis Diagnosis: Malignant Melanoma, Spindle Cell Type Discussion Malignant melanoma(MM) is aptly named "the great masquerader" for morphologically it can imitate a variety of neoplasms from different categories including lymphoma, sarcoma, germ cell tumor, and carcinoma. In this patient, we were aware of a spindle cell melanoma that had been removed from his scalp several months earlier so the cytologic diagnosis was made with little di fficulty. Most large series on MM cytology show lymph nodes as the most commonly aspirated anatomic site. The morphologic spectrum of this tumor is listed in Table 23. Table 56. Malignant Melanoma – Variants • Epithelioid • Pleomorphic/Anaplastic • Spindle cell • Carcinoma-like • Lymphoma-like • Myxoid • Clear cell   Table 57. Melanoma – specificity of morphologic features [Perry et al. Acta Cytol 1986;30:385] diagnostic melanin with malignant cells (40%) relatively diagnostic appropriate clinical history many isolated cells characteristic cell shapes and nuclear positions accessory criteria bi-/multinucleated cells macronucleoli intranuclear invaginations variable features nuclear chromatin pattern nuclear irregularity number/size of nucleoli Epithelioid Metastatic Non-Small Cell Tumors A single cell pattern can be found often in smears of MM potentially causing confusion with large cell lymphoma. Unlike smears of conventional large cell lymphoma, MM cells typically exhibit frequent binucleation, occasional intracytoplasmic nuclear inclusions, and absent LGBs. The constant presence of mirror-image nuclei in some aspirates of MM forces one to consider ALCL and HL. The typical reactive lymphocyte milieu of HL is different from MM. ALCL can be much more difficult to distinguish from MM because both can have single cell pattern with loose cell groupings, both can have binucleation, multinucleation, and wreath shaped nuclei, and both can have few LGBs on the smear. Immunocytochemistry may be necessary. Of course, melanin pigment within malignant cells is the only true morphologic indicator of MM, but amelanotic forms of MM are frequent enough in aspirates that this is finding is only useful when present. Non-small cell carcinoma in lymph nodes aspirates almost always has a clustered architecture so that distinction from melanoma or large cell lymphoma is not problematic. LGBs are absent from the smear if only carcinoma is aspirated, but present if some non-neoplastic lymphocytes are also captured. Origin of most metastatic non-small cell carcinomas cannot be predicted from the morphology alone. Cells with numerous coarse cytoplasmic vacuoles are typical of clear cell carcinomas, and thus primary tumors of the kidney, ovary, and lung are likely possibilities. Metastatic Squamous cell carcinoma is the most common indication for lymph node FNA. Most diagnoses are straightforward, but one pitfall is cystic degeneration in which one may encounter only necrotic or amorphous debris and mistake the cancer for benign cyst contents. Metastatic Seminoma: generally involves the deep lymph nodes of the chest or abdomen distribution as both single cells and clustered groups germ cell nuclei large, pleomorphic with a single nucleolus cell vacuoles are common and typically large blister-like background stroma - strands of cytoplasm and proteinaceous fluid are arranged in a reticular or linear network - labeled "tigroid pattern". Background neither universally present, nor entirely specific for this tumor. lymphocytes are common in seminoma, and thus LGBs may be present Spindle Cell Lesions, Metastatic and Primary The spindle cell MM in case 9 produces a differential diagnosis that includes other spindle cell lesions(Table 24). Table 58. Spindle Cell Lesions of Lymph Nodes • Metastatic Spindle cell sarcoma • Metastatic Spindle cell melanoma • Metastatic Spindle cell(sarcomatoid) carcinoma • ALCL, spindle cell variant • Inflammatory pseudotumor • Kaposi sarcoma Only a few of these are discussed. Lymph nodes are an infrequent terminal for metastatic sarcoma. Most of these are in fact examples of round cell sarcoma rather than spindle cell sarcoma. Synovial sarcoma(SS) is the only "common" spindle cell sarcoma that has a high incidence of lymph node metastasis. Smears are high cellular composed of a monotonous population of extremely bland spindle cells with ovoid finely granular nuclei, smooth nuclear outlines, and very scant amounts of cytoplasm that can taper on one or both sides of the nucleus. Rarely, one can espy an acinar grouping that reflects the glandular pattern seen in some examples of this tumor. SS is cytokeratin positive, CD34 negative. Sarcomatoid ALCL is characterized by containing cells with elongated spindle shaped nuclei admixed with pleomorphic cells with macronucleoli and broad or slender elongated cytoplasmic processes. Some of these aspirates show cells closely attached to branching capillaries. To further compound morphologic interpretation, LGBs may be sparse to absent. Table 59. Follicular Dendritic Cell(FDC) Sarcoma young -middle age nodal and extranodal tissue patterns: fascicular, diffuse, whorled, trabecular immuno: positive CD21, CD35, vimentin, EMA, actin moderately aggressive nuclei are intermediate in size with smooth borders and small inapparent nuclei. Mitotic figures and isolated nucleomegaly can be apparent. Cytoplasm is minimal but thin cytoplasmic processes can be found in many cells. Lymph node involvement by Kaposi sarcoma occurs in an endemic form in African children, and in immune deficient states such as renal transplant patients, and HIV+ homosexual males. In the non-endemic form patients also have cutaneous disease which is a very helpful clinical clue. In the advanced lesion nearly the entire node is replaced by bland spindle cells with an intersecting fascicular pattern. Small vascular slits punctuate this spindle cell proliferation with extravasated red cells and eosinophilic hyaline globules. Smears are variably cellular with abundant red cells. Cells are aggregated into loose and tightly united clusters, have ovoid to elliptical nuclear shapes, no visible nucleoli, and scant tapering cytoplasm. Hyaline globules are usually difficult to find. A definitive diagnosis nearly always requires immunphenotyping which shows that spindle cells are CD31 and CD34 positive. References for All Cases