Case-Based Approach in Fine Needle Aspiration Cytology Pranab Dey
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General CytologyCHAPTER 10

 
Questions
 
Problem 10.1
A 65-year-old male presented with diffuse 3 cm × 4 cm × 3 cm enlarged thyroid for last 8 months.
  1. What is the most likely diagnosis from Figure 10.1?
    1. Lymphocytic thyroiditis
    2. Medullary carcinoma
    3. Insular carcinoma
    4. Non-Hodgkin lymphoma
  2. What further investigation is needed to confirm your diagnosis?
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:
349
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Fig. 10.1:
350
 
Problem 10.2
An 8-year-old boy presented with upper abdominal swelling for 15 days. USG shows a 6 cm diameter para-aortic swelling with areas of calcification.
  1. What is the most likely diagnosis from Figure 10.2?
    1. Non-Hodgkin lymphoma
    2. Rhabdomyosarcoma
    3. Neuroblastoma
    4. Wilms’ tumor
  2. What further investigation could be done to confirm the diagnosis?
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Fig. 10.2:
351
 
Problem 10.3
A 9-month-old male child presented with 4 cm swelling in the maxillary region for 7 months. The most likely diagnosis from Figure 10.3 is:
  1. Melanotic neuroectodermal tumor of infancy (melanotic progonoma)
  2. Rhabdomyosarcoma
  3. Neuroblastoma
  4. Burkitt's lymphoma
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Fig. 10.3:
352
 
Problem 10.4
An 11-year-old female had weakness in lower legs, backache, bladder instability and difficulty in squatting. CT scan showed an intradural, extramedullary cystic lesion at D12-L1 level, compressing and displacing the spinal cord. CT-guided FNAC yielded 2 mL straw colored fluid. The most likely diagnosis from Figure 10.4 is:
  1. Ependymoma
  2. Schwannoma
  3. Cystcercosis
  4. Hydatid cyst
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Fig. 10.4:
353
 
Problem 10.5
Match the fungus from Figure 10.5
  1. 1. Mucormycosis
  2. 2. Aspergillosis
  3. 3. Histoplasmosis
  4. 4. Cryptococcus
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Fig. 10.5:
354
 
Problem 10.6
A 12-year-old boy presented with 8 cm diameter lower abdominal mass for 15 days. What is the most likely diagnosis from Figure 10.6?
  1. Rhabdomyosarcoma
  2. Desmoplastic small round cell tumor
  3. Neuroblastoma
  4. Germ cell tumor
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Fig. 10.6:
355
 
Problem 10.7
A 48-year-old female presented with 4.5 cm diameter swelling in the posterior part of neck near the occipital region. FNAC yielded thick mucoid material. The possible diagnosis from Figure 10.7 is:
  1. Metastatic renal cell carcinoma
  2. Adenoid cystic carcinoma
  3. Skin adnexal tumor
  4. Chrodoma
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Fig. 10.7:
356
 
Problem 10.8
A 38-year-old male was operated for carcinoma of right tonsil 2 year back. Now the patient presented with 1.5 cm diameter swelling in the right submandibular region for few days.
The most likely diagnosis from Figure 10.8 is:
  1. Benign salivary gland epithelial cells
  2. Metastatic carcinoma
  3. Reactive lymphoid hyperplasia
  4. Pleomorphic adenoma
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Fig. 10.8:
357
 
Problem 10.9
A 46-year-old male presented with 5 cm diameter swelling in right shoulder region. The swelling is soft-to-firm and fixed to deeper tissue. The patient also had fever, cough and hemoptysis for last 15 days. Chest radiograph of the patient showed 5 cm diameter consolidated area in right upper lobe of lung.
The most likely diagnosis from Figure 10.9 is:
  1. Metastatic squamous cell carcinoma from lung
  2. Inflammatory lesion
  3. Metastatic large cell anaplastic carcinoma
  4. Skin adnexal tumor
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Fig. 10.9:
358
 
Problem 10.10
A 15-year-old female presented with 2 cm diameter swelling in left 1st metacarpal bone swelling for 3 months. MRI showed a bony lesion. The most likely diagnosis from the Figure 10.10 is:
  1. Giant cell tumor of tendon sheath
  2. Giant cell tumor of bone
  3. Aneurysmal bone cyst
  4. Osteoblastoma
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Fig. 10.10:
359
 
Problem 10.11
A 21-year-old female presented with fever and generalized weakness for 2 months. USG revealed multiple retroperitoneal lymph node 3 to 4 cm diameter. FNAC of the lymph node was done along with flow cytometry (Fig. 10.11). The most likely diagnosis is:
  1. Reactive lymphoid hyperplasia
  2. Non-Hodgkin lymphoma (B cell) type possibly follicular
  3. Small lymphocytic lymphoma
  4. Germ cell tumor
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Fig. 10.11:
360
 
Problem 10.12
A 43-year-old female was operated for an ovarian tumor and histopathology of which is shown in Figure 10.12a. After 6 months, the patient developed a 6 cm mass in the pouch of Douglas. FNAC of the mass is shown in Figure 10.12b, c, and d. The most likely diagnosis is:
  1. Metastatic adenocarcinoma
  2. Metastatic clear cell carcinoma
  3. Metastatic granulosa cell tumor
  4. Metastatic immature teratoma
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Fig. 10.12:
361
 
Problem 10.13
A 46-year-old male presented with abdominal discomfort and pain for 15 days. USG of his abdomen revealed multiple space occupying lesions about 3 to 5 cm diameter in both liver and spleen. The lesions were vascular. Cell block from liver FNAC shows CD34 positive cells.
  1. The most likely diagnosis from Figure 10.13 is:
    1. Metastatic adenocarcinoma
    2. Hepatocellular carcinoma
    3. Benign hepatocytes
    4. Angiosarcoma
  2. What immunostaining should be done to prove the diagnosis?
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Fig. 10.13:
362
 
Problem 10.14
A 25-year-old female presented with 5 cm diameter firm fixed right axillary lymph node for 7 days. She had a surgery in right forearm and the nature of the lesion is not known. The most likely diagnosis from Figure 10.14 is:
  1. Metastatic epithelioid sarcoma
  2. Metastatic leiomyosarcomas
  3. Metastatic melanoma
  4. Metastatic liposarcoma
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Fig. 10.14:
363
 
Problem 10.15
A 45-year-old female had cough and hemoptysis for 2 months. He had 4 cm space occupying lesion in lower lobe of right lung. The most likely diagnosis from Figure 10.15 is:
  1. Squamous cell carcinoma
  2. Small cell carcinoma
  3. Adenocarcinoma
  4. Large cell carcinoma
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Fig. 10.15:
364
 
Problem 10.16
A 39-year-old female had cough for 9 months. Her X-ray of the lung revealed a 4.5 cm diameter well circumscribed space occupying lesion in the apex of the right lung. The most likely diagnosis from the Figure 10.16 is:
  1. Small cell carcinoma
  2. Squamous cell carcinoma
  3. Adenocarcinoma
  4. Carcinoid tumor
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Fig. 10.16:
365
 
Problem 10.17
A 41-year-old male had abdominal discomfort for 3 months. USG of liver showed a 4 cm diameter space occupying lesion in liver. The most likely diagnosis from Figure 10.17 is:
  1. Chronic inflammation
  2. Metastatic small cell carcinoma
  3. Metastatic neuroendocrine tumor
  4. Non-Hodgkin lymphoma of liver
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Fig. 10.17:
366
 
Problem 10.18
A 15-year-old male had abdominal pain for 2 months. USG of his abdomen revealed a 5.5 cm diameter retroperitoneal mass with foci of calcification. The most likely diagnosis from Figure 10.18 is:
  1. Non-Hodgkin lymphoma
  2. Rhabdomyosarcoma
  3. Ganglioneuroblastoma
  4. Reactive lymphoid tissue
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Fig. 10.18:
367
 
Problem 10.19
A 15-year-old boy was operated for an osteolytic bony swelling of lower end of femur. Histopathology of the lesion is depicted in Figure 10.19A. After 6 months, the patient developed 2 cm diameter firm swelling over the forehead. FNAC of the swelling was done (Fig. 10.19). The most likely diagnosis is:
  1. Skin adnexal lesion
  2. Langerhans cell histiocytosis
  3. Metastatic osteosarcoma
  4. Rhabdomyosarcoma
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Fig. 10.19:
368
 
AnswerS
 
Problem 10.1
  1. d. Non-Hodgkin lymphoma
 
Discussion
Discrete population of round monomorphic cells with scanty deep blue cytoplasm indicates the possibility of non-Hodgkin lymphoma. Lymphocytic thyroiditis shows polymorphic population of lymphoid cells. Medullary carcinoma consists of discrete cells with moderate cytoplasm that often contain fine red granules. The clusters of normal thyroid follicular cells are usually absent in medullary carcinoma. Insular carcinoma shows frequent clusters of thyroid follicular cells and also microfollicles. The chromatin of the nuclei is more clumped in such tumor.
  1. Flow cytometry (FCM) or immunocytochemistry on cell block material is needed to show light chain restriction, and immunophenotyping. At times, florid lymphocytic thyroiditis shows abundant reactive lymphoid cells and may create diagnostic difficulties. FCM is helpful in such cases.
 
Problem 10.2
  1. c. Neuroblastoma
  2. Immunocytochemistry should be done in this case from the cell block material. Neuroblastoma cells are positive for NB-84, NSE and CD99. Neuroblastoma also shows characteristic small dense core neurosecretory granules and abundant longitudinally arranged microtubules on electron microscopy.
 
Discussion
In this case, the presence of round cells, neurofibrillary material and absence of lymphoglandular bodies indicate the diagnosis of neuroblastoma. The presence of calcification on radiology also suggests the diagnosis of neuroblastoma. Rhabdomyosarcoma cells show frequent bi and multinucleation, and occasionally strap cells. Absence of lymphoglandular bodies in the background excludes the possibility of lymphoma. Extra renal localization of the tumor also eliminates the possibility of Wilms’ tumor. As mentioned above, immunocytochemistry is always necessary for further confirmation of such cases.
 
Problem 10.3
  1. Melanotic neuroectodermal tumor of infancy (melanotic progonoma)
 
Discussion
The following features indicate the diagnosis of melanotic neuroectodermal tumor of infancy (MNTI):369
  • The presence of discrete population of round to oval cells with scanty cytoplasm
  • Stippled chromatin
  • Characteristic brownish melanin pigment in the cytoplasm.
The cells of MNTI are positive for HMB-45, NSE and EMA. The tumor is typically seen in infant less than one year of age. The tumor typically occurs in head and neck region. MNTI develops from the neural crest cells. This is a rapid growing benign tumor and is locally aggressive.
Rhabdomyosarcoma and neuroblastoma are unlikely in this infant because melanin pigment is absent in these tumors. Burkitt's tumor shows starry sky appearance with many histiocytes in the midst of immature lymphoid cells. The cells are twice the size of lymphocytes with vacuolated cytoplasm and prominent nucleoli.
 
Further Reading
  1. Gochhait D, Mitra S, Saikia UN, et al. Letter to the editor: Fine needle aspiration cytology of Melanotic neuroectodermal tumor of infancy. Diagn Cytopath (in press).
 
Problem 10.4
  1. Hydatid cyst
 
Discussion
The microphotographs typically show tegument layer, and scolices having hooklets of hydatid. Hydatid disease is caused by the tapeworm Echinococcus granulosus. This infection is transmitted from sheeps or cattles to humans orally via eggs shed in the feces of infected animals. Primary hydatid disease is usually seen in the liver, spleen, and lungs. Musculoskeletal involvement by hydatid is uncommon (2.5%). It may involve the pelvis, sacrum, long bones, skull, and spine. Spinal involvement is rare, with an incidence of less than 1%.
 
Problem 10.5
  1. 4. Cryptococcus
  2. 2. Aspergilosis
  3. 1. Mucormycosis
  4. 3. Histoplasmosis
 
Discussion
Cryptococci are 5 to 10 µ diameter small, round structure with thick outer capsule. Mucormycosis is 6 to 50 µ diameter structure and they are broad based, non-septate, with right-angled branching at irregular interval. Aspergillus is 6 to 10 µ width. They show uniform septation and acute angle branched hyphae. Histoplasma is small round 2-5 µ in diameter. They show narrow budding and usually remain inside the macrophages (Table 10.1).370
Table 10.1   Different fungal morphology
Organism
Morphology
Diameter
Stains
Differential diagnosis
Cryptococcus
Round, thick outer capsule. Narrow based budding
5 to 10 ε diameter
India ink
Blastomyces, Histoplasma
Aspergillus
Uniform septate, acute angle branching hyphae
3–6 micron width
PAS, Mucicarmine, Methenamine silver
Candida species
Mucor
Broad-based, non-septate, right- angled branching at irregular interval
6 to 50 micron in diameter
Grocott-Gomori and methenamine-silver
Other fungi such as Aspergillus
Histoplasma
Narrow budding, usually inside the macrophages
Small round 2–5 ε in diameter
Methenamine silver
Cryptococcus and Blastomycosis
 
Problem 10.6
  1. Desmoplastic small round cell tumor
 
Discussion
The following features suggest the diagnosis of desmoplastic round cell tumor (DSRCT):
  • Multiple small clusters and discrete round cells
  • The cells have scanty cytoplasm and predominantly monomorphic nuclei
  • Stromal fragment
  • CK, vimentin and desmin positive cells.
Rhabdomyosarcoma and neuroblastoma are excluded as the cells are positive for both CK and desmin (Table 10.2). The overall cytomorphology was not consistent with germ cell tumor. The germ cell tumors usually show vacuolated background and the individual cells have scanty vacuolated cytoplasm and large prominent nucleoli.
Table 10.2   Immunocytochemistry
NB-84
Myo D1
CK
Desmin
WT1
Mic-2 (CD99)
Rhabdomyosarcoma
+
-
+
+
-
Neuroblastoma
+
-
-
-
-
+
Desmoplastic small round cell tumor
-
+
+
+
-
Acknowledgement: This case is taken from the book by Dey P. Diagnostic Cytology. First edition, 2014. Jaypee Brothers Medical Publishers Pvt Ltd. New Delhi.371
 
Problem 10.7
  1. Chordoma
 
Discussion
In the index case, the following features suggest the diagnosis of chordoma:
  • Abundant chondromyxoid material
  • Classical Physaliferous cell: Large cell with abundant bubbly vacuolated cytoplasm.
Chordoma is the tumor of notochord and is commonly seen in the sacral and spheno-occipital region. In case of metastatic renal cell carcinoma, there may be large clear cells with centrally placed nuclei. However, the cells do not show typical bubbly vacuolated cytoplasm as seen in Physaliferous cells. Moreover, the chondromyxoid material is not seen in renal cell carcinoma. Adenoid cystic carcinoma shows hyaline globules and the cells contain scanty cytoplasm. The index case does not resemble any known skin adnexal tumor.
 
Further Reading
  1. Finley JL, Silverman JF, Dabbs DJ, et al. Chordoma: diagnosis by fine-needle aspiration biopsy with histologic, immunocytochemical, and ultrastructural confirmation. Diagn Cytopathol. 1986;2(4):330–7.
 
Problem 10.8
  1. Benign salivary gland epithelial cells
 
Discussion
In this index case, there are multiple clusters of benign salivary ductal and acinar cells. The benign ductal cells may be confused as malignant cells, and therefore one should be careful in the interpretation of such cases. Metastatic carcinoma shows cells with enlarged and pleomorphic nuclei.
 
Problem 10.9
  1. Metastatic large cell anaplastic carcinoma
 
Discussion
In the index case, the following features suggest the diagnosis of metastatic large cell anaplastic carcinoma:
  • History of lung lesion
  • Large pleomorphic cells with enlarged nuclei
  • Multilobated pleomorphic cells
  • Neutrophils sticking with the tumor cells.
The individual cell morphology of squamous cell carcinoma is different. The cells are oval to polyhedral with central hyperchromatic nuclei. Fiber and tadpole cells are frequently seen in squamous cell carcinoma. Skin adnexal tumor is unlikely in this case as the presence of large 372clusters of malignant cell along with the history of lung lesion is highly suggestive of metastatic lung lesion.
 
Problem 10.10
  1. Giant cell tumor of bone
 
Discussion
In the index case, the following features indicate the diagnosis of giant cell tumor of bone:
  • Bony lesion in MRI
  • Multiple osteoclastic giant cells
  • Spindle-shaped stromal cells.
Giant cell tumor of tendon sheath occurs in the soft tissue. It is difficult to differentiate from giant cell tumor of bone on the basis of FNAC. Aneurysmal bone cyst yields many foamy histiocytes. Osteoblastoma is a remote possibility in the index case.
 
Problem 10.11
  1. Non-Hodgkin lymphoma (B cell) type possibly follicular
 
Discussion
In the index case, the cells are CD45 positive and light chain restriction indicate the diagnosis of non-Hodgkin lymphoma (NHL). Positive CD19, CD20 and CD10 markers indicate B cell follicular lymphoma.
Acknowledgement: This case is taken from the book by Dey P. Diagnostic Cytology. First edition, 2014. Jaypee Brothers Medical Publishers Pvt Ltd. New Delhi.
 
Problem 10.12
  1. Metastatic clear cell carcinoma
 
Discussion
In this index case, the microphotograph of the histopathology section in Figure 10.12A shows clear cell carcinoma of ovary. The cytology smears (Fig. 10.12B, C, D) show clusters of malignant cells having round to oval nuclei and abundant clear cytoplasm. Cytology smears along with previous histopathology are consistent with recurrence of clear cell carcinoma.
 
Problem 10.13
  1. d. Angiosarcoma
  2. Angiosarcoma is positive for CD34, CD31 and Von Wilebrand factor. The cells may occasionally show cytokeratin and EMA.373
 
Discussion
In this index case, the following features favor the diagnosis of angiosarcoma:
  • Scattered cells and predominant perivascular arrangement of cells
  • The cells show oval to elongated nuclei with blunt ends
  • CD34 positive cells.
Metastatic adenocarcinoma shows columnar looking cells with vacuolated cytoplasm. Gland formation is also noted. Hepatocellular carcinoma often shows trabecular arrangement of cells and many discrete bare nuclei. The cells of hepatocellular carcinoma are polyhedral in appearance with large nuclei having macronucleoli.
Acknowedgement: This case is donated by Dr Priya Singh, Assistant professor, Department of Cytology, PGIMER, Chandigarh.
 
Problem 10.14
  1. Metastatic melanoma
 
Discussion
In this index case, the following features indicate the diagnosis of metastatic melanoma:
  • Abundant discrete malignant cells
  • Cells with moderate cytoplasm and large nuclei with macronucleoli
  • Presence of melanin pigment within the cell.
The presence of melanin within the cell eliminates the possibilities of various metastatic sarcomas.
 
Problem 10.15
  1. Adenocarcinoma
 
Discussion
In the present case, the following features suggest the diagnosis of adenocarcinoma:
  • Glandular pattern of cells
  • TTF-1 and CK 7 positivity
The cells of adenocarcinoma are positive for TTF 1 and CK 7, whereas the cells of squamous cell carcinoma are negative for TTF and CK7, and positive for CK 5/6 and p63. Small cell carcinoma is positive for TTF and chromogranin (Table 10.3).
Table 10.3   Immunocytochemistry of lung tumors
Tumor
CK7
CK5/6
TTF-1
Chromogranin
Adenocarcinoma of lung
+
+
Squamous cell carcinoma of lung
+
Small cell carcinoma
+
+
+ = positive, – =negative
374
 
Problem 10.16
  1. Carcinoid tumor
 
Discussion
In this index case, the following features indicate the diagnosis of carcinoid of lung:
  • Loose clusters and rosette like arrangement of cells
  • Monomorphic cell
  • Cells with reddish granules
  • Salt and pepper chromatin
The immunocytochemistry of carcinoid lung shows chromogranin, synaptophysin and CD56 positivity.
The differentiating points of carcinoid from other tumors are highlighted in the Table 10.4:
Table 10.4   Differentiating features of lung tumors
Small cell carcinoma
Squamous cell carcinoma
Adenocarcinoma
Carcinoid
Cell clusters
Discrete
Present
Glandular
Discrete
Indian file arrangement
Present
Absent
Absent
Absent
Nuclear threading
Present
Absent
Absent
Absent
Cell cytoplasm amount
Scanty to nil
Moderate
Moderate
Moderate, reddish granular
Cytoplasm character
Thin rim of basophilic
Orangeophilic dense cytoplasm
Vacuolated
Reddish granular
Nuclear molding
Present
Absent
Absent
Absent
Nucleus
Small, one to two times larger than lymphocyte
Relatively low N/C ratio, small nucleus
Large
Larger
Chromatin
Granular, and salt and pepper
Irregular coarse
Fine
Salt and pepper
Immunochemistry
Chromogranin
Synaptophysin
TTF
Positive
Positive
Positive
Negative
Negative
Negative
Negative
Negative
Positive
Positive
Positive
Variable positivity
Electron microscopy
Neuroendocrine granules
Desmosomal junction
Nothing significant
Neuroendocrine granules
 
Further Reading
  1. Dey P. Fine needle aspiration cytology: Interpretation and diagnostic difficulties. Second Edition. Jaypee Brothers Medical Publishers Pvt Ltd.  India.  375
 
Problem 10.17
  1. Non-Hodgkin lymphoma of liver
 
Discussion
In the index case, the following features indicate the diagnosis of non-Hodgkin lymphoma:
  • Discrete round monomorphic cells with deep blue cytoplasm
  • Background lymphoglandular bodies
Primary non-Hodgkin lymphoma (NHL) of liver is rare. The common types of NHL of liver include DLBCL and Burkitt's lymphoma. Metastatic small cell carcinoma may simulate NHL. The cells often show nuclear molding and crushing artifact. Neuroendocrine carcinoma shows discrete cells with moderate amount of reddish granular cytoplasm. Nuclei often show salt and pepper chromatin. Chronic inflammation shows only mature lymphocytes.
In the cases of primary NHL of liver, immunocytochemistry on cell block is mandatory.
 
Problem 10.18
  1. Ganglioneuroblastoma
 
Discussion
In this index case, the features suggestive of ganglioneuroblastoma include:
  • Small round cells with rosette
  • Many ganglionic cells with abundant cytoplasm and central monomorphic nuclei.
The possibility of non-Hodgkin lymphoma is excluded due to clustering and rosette like arrangement of the cells. Rhabdomyosarcoma shows discrete cells with frequent bi and multi nucleation. The possibility of reactive lymphoid hyperplasia is totally ruled out in absence of any polymorphic lymphoid cells and the presence of rosettes.
 
Problem 10.19
  1. Metastatic osteosarcoma
 
Discussion
The boy was operated for osteosarcoma of femur (Fig. 10.19a). The cytology smear is suggestive of metastatic osteosarcoma due to following reasons:
  • History of osteosarcoma
  • Large bizarre tumor cells with prominent nucleoli
  • Deep pink osteoid material
The cytology pictures do not resemble any known adnexal tumors. The possibility of Langerhans cell histiocytosis is ruled out due to the absence of eosinophils and large cells with cleaved nuclei. The clinical history, bony lesion and the presence of osteoid material exclude the possibility of rhabdomyosarcoma.