Fig. 7.1
UCNT, Regaud type , isolated tumor cells and inflammatory background, May-Grünwald Giemsa (MGG)
Fig. 7.2
UCNT, Schminke type, spindle-shaped cells, Papanicolaou
7.1.3 Ancillary Techniques
Immunocytochemistry (ICC) shows positivity for cytokeratin, EMA, EBV, and EBER. Reactivity to CEA and S-100 is variable, while positivity for CD23 and CD30 is present in some cases. EBV detection is also possible by PCR method; however, EBER1 in-situ hybridization is more sensitive and specific [4].
7.1.4 Differential Diagnosis
UCNT should be differentiated from non-Hodgkin and Hodgkin lymphoma, germ cell tumors, squamous cell carcinoma, or any metastatic poorly differentiated carcinoma or small round cell tumor from other sites. Large, atypical nuclei reminiscent of Reed-Sternberg cells and a mixture of lymphocytes, eosinophils, plasma cells, and even granulomas simulate Hodgkin lymphoma. CD15 may help, but this marker is not always positive in cytological samples of Hodgkin lymphoma. A population of completely dissociated tumor cells of UCNT may simulate large cell non-Hodgkin lymphoma as well as other small round cell tumors of childhood. EMA and CD30 are useless in differentiating UCNT from lymphoma [5]. A broader spectrum of antibodies is necessary to rule out small round cell tumors.
7.2 Pilomatricoma
Pilomatricoma (PMC) is also called pilomatrixoma, or calcified epithelioma of Malherbe. It is a benign tumor originating from the hair matrix, which presents as a nodule in subepidermal location. It is seen in children and young adults, most commonly in the head and neck area and upper extremity [6].
Smears variably show sheets of basaloid cells or round cells, ghost or shadow cells, foreign body giant cells and calcifications (Figs. 7.3, 7.4, 7.5, and 7.6) [7].
Fig. 7.3
Pilomatricoma. Ghost cells and squamous debris , MGG
Fig. 7.4
Pilomatricoma. Giant cell , MGG
Fig. 7.5
Pilomatricoma. Calcifications , MGG
Fig. 7.6
Pilomatricoma. Round cells which should be differentiated from round cell tumors, MGG
PMC should be differentiated from round cell sarcomas, especially rhabdomyosarcoma and Ewing sarcoma. Ruptured epidermal cyst produces a foreign body reaction and should be differentiated from other cases where a lot of foreign body giant cells are seen [8].
7.3 Salivary Tumors
Salivary tumors may arise in children. The most common entities are mucoepidermoid carcinoma and acinic cell carcinoma. The prognosis is better than in adults [9, 10]. Cytologically salivary tumors do not differ significantly from their adult counterparts (Figs. 7.7 and 7.8) [11].
Fig. 7.7
Mucoepidermoid carcinoma . Mucoid background and intermediate and mucus-secreting cells, MGG
Fig. 7.8
Pleomorphic adenoma . Myoepithelial cells and chondromyxoid background, MGG
Benign and malignant tumors may occur in the tissues below, within, or above salivary glands, especially in the parotid area. The precise location of the neoplasm is very helpful in the differential diagnosis. In our experience, Langerhans cell histiocytosis, metastatic melanoma, and rhabdomyosarcoma have been misdiagnosed because the lesions were presumed to originate from the parotid gland.
7.4 Germ Cell Tumors
7.4.1 General
Germ cell tumors (GCT) are heterogeneous neoplasms, benign and malignant, which arise from germ cells. Germ cells originate in the wall of the yolk sac and migrate through the body of the embryo into the developing gonads. If they are arrested on their pathway they may become the source of GCT. The migration, therefore, explains various locations of GCT.
Histologic classification of GCTs includes:
Tumors of one histologic type (pure forms)
Teratoma
Seminoma/dysgerminoma
Embryonal carcinoma
Yolk sac tumor (endodermal sinus tumor)
Choriocarcinoma (trophoblastic tumor)
Tumors of more than one histological type (mixed forms)
Mixed forms are GCT with a combination of two or more of the above listed pure forms
The incidence rate of malignant GCT in children and adolescents is estimated at less than 1/100,000. This accounts for approximately 3% in girls and 10% in boys of all cancers in this age group [12]. The overall incidence for GCT is higher because of many benign ovarian teratomas. Very precise data for children are difficult to obtain because many studies include GCT of all ages. Additionally, there are great geographical variations in incidence of testicular GCT, ranging from less than 2 to over 10/100,000, in all age groups [13]. The predisposing factors are undescended testis, testicular atrophy, and dysgenetic ovaries.
GCT in children and young adults have a bimodal distribution of occurrence: at 2 years and at 15–20 years.
Considering all GCTs and both sexes, about 80% of them are benign and 20% are malignant, but the majority of GCT in girls are benign while the majority of GCT in males are malignant. The frequency of specific GCT entities varies with sex. In girls, the most frequent benign GCT is teratoma while the most frequent malignant GCT is dysgerminoma. The most frequent GCT in boys is yolk sac tumor. Choriocarcinoma is extremely rare.
GCT are located in the gonads (ovaries and testes) and at various extragonadal sites in the midline: intracranial, mediastinum, retroperitoneum, sacrococcygeal region. The gonadal locations are more common. Main symptoms of GCT are presence of a lump, abdominal or chest pain (depending on tumor location), extensive growth, early onset of puberty, and frequent urination. Elevated levels of alpha fetoprotein and human chorionic gonadotropin are present with some GCT.
7.4.2 Cytomorphology and Ancillary Techniques
7.4.2.1 Teratoma
Teratoma is a tumor composed of different tissues derived from ectoderm, endoderm, and mesoderm. Teratomas can be benign or malignant, often cystic and multiloculated. Monodermal teratomas are composed of tissues from only one germinal layer. Mature teratomas contain only well-differentiated tissues, while immature teratomas also contain fetal tissues. Teratomas with somatic-type malignancies contain teratomatous elements and a malignant component normally seen in other tissues and organs.
Mature teratomas can be predominantly cystic or predominantly solid. Smears from the latter are often poorly cellular. Fluid from predominantly cystic teratomas most often contains anucleated squames and cellular debris. In addition to squamous epithelium, smears can contain glandular epithelium, brain tissue, cartilage, bone, fat, and connective tissue (Figs. 7.9 , 7.10 , and 7.11 ).
Fig. 7.9
Teratoma, tubules and epithelial elements , hematoxylin-and-eosin safran (HES)
Fig. 7.10
Teratoma, fat and mesodermal structures , HES
Fig. 7.11
Teratoma, cell block , HES
Smears from immature teratomas seldom contain immature elements because tumors are mainly composed of mature elements. The most commonly encountered immature elements are from the neuroectoderm. Cells are small, round-to-oval with scant, pale cytoplasm, hyperchromatic, uniform nuclei without nucleoli (Fig. 7.12 ). Cells can be arranged in tight clusters, nuclear moulding and neuropil may be present, and the morphologic picture can resemble neuroblastoma. Other immature tissues include fetal cartilage, muscle, kidney, and undifferentiated mesenchyme. ICC is not very helpful in making the right diagnosis in cytology.
Fig. 7.12
Immature teratoma with small, round cells with hyperchromatic nuclei and scant cytoplasm, MGG ×40
Teratomas with somatic-type malignancies are seldom recognized from FNA smears because all pathognomonic tumor components are rarely present in the smear. The most commonly present malignant component is a sarcoma: rhabdomyosarcoma, leiomyosarcoma, malignant peripheral nerve sheath tumor, osteosarcoma, chondrosarcoma, PNET. Other possible components are nephroblastoma, neuroblastoma, adenocarcinoma, squamous carcinoma, and neuroendocrine carcinoma (Fig. 7.13 ).
Fig. 7.13
Teratoma with somatic type malignancy, neuroendocrine carcinoma as the malignant teratoma component, MGG ×40
7.4.2.2 Seminomas and Dysgerminomas (Germinomas)
Germinomas are poorly differentiated tumors of the germ cells [14]. Testicular germinomas are called seminomas, ovarian germinomas are called dysgerminomas. The term germinoma is usually restricted for the extragonadal sites.
FNA smears from germinomas are highly cellular with predominantly dissociated cells and naked nuclei. Some loosely aggregated cell groups may be present. Tumor cells are large, round, uniform, with high nuclear/cytoplasmic ratio. Nuclei have fine chromatin with single prominent nucleoli. Sometimes several smaller nuclei are present. Cytoplasm is clear with glycogen vacuoles. Background contains inflammatory cells like lymphocytes, plasma cells, and histiocytes, and sometimes even granulomas and a lacy, tigroid material (Figs. 7.14, 7.15, 7.16 , and 7.17 ).
Fig. 7.14
Seminoma showing large germinal cells with admixed lymphocytes and tigroid background , HES
Fig. 7.15
Seminoma. Prominent atypia , MGG
Fig. 7.16
Seminoma. Cell block , HES
