A 24-year-old male with complicated medical history including obesity, Asperger’s syndrome, and diabetes mellitus, presented with altered mental status. Head CT at ED shows multiple brain mass lesions. Additional PET/CT reveals numerous bilateral lung nodules, multiple hypermetabolic soft tissue lesions in the musculature, a possible kidney lesion, and a right abdominal wall subcutaneous lesion measuring 2.8 cm. FNA of the abdominal wall subcutaneous lesion was performed.

 

Authors

• Daisy Sun, MD PhD, Miami Valley Hospital, Dayton, OH
• Mia Wang, The Seven Hills School, Cincinnati, OH

click on image for larger version

Figure 1	Figure 2	Figure 3
Figure 4	Figure 5	Figure 6

Images 1-6:

• Figure 1: Rapid on-site evaluation (ROSE) FNA material of the right abdominal wall lesion, smear, Diff-Quik stain, x 100 magnification.
  
  
• Figure 2: Rapid on-site evaluation (ROSE) FNA material of the right abdominal wall lesion, smear, Diff-Quik stain, x 200 magnification.
  
  
• Figure 3: Rapid on-site evaluation (ROSE) FNA material of the right abdominal wall lesion, smear, Papanicolaou stain, x 400 magnification.
  
  
• Figure 4: Core biopsy of the right abdominal wall lesion, x 200 magnification.
  
  
• Figure 5: Core biopsy of the right abdominal wall lesion, IHC PAX 8, x 40 magnification.
  
  
• Figure 6: Core biopsy of the right abdominal wall lesion, special stain PASD , x 200 magnification.

Questions:

1. Metastasis to which of the following locations is more common in alveolar soft part sarcoma (ASPS) than in any other soft tissue sarcoma?
   
   
1. Bone
2. Brain
3. Liver
4. Lung
5. Lymph node
   
   
2. Which of the following special stains is most helpful in diagnosing alveolar soft part sarcoma (ASPS)?
   
   
   1. Colloidal iron
   2. GMS
   3. PAS with diastase
   4. PAS without diastase
   5. Warthin-Starry
      
      
3. Which of the following immunoprofiles is most compatible with ASPS?
   
   
   1. AE1/3 +, PAX8 +, TFE3 +, S100 -, SOX10 -, CD68 -
   2. AE1/3 -, PAX8 -, TFE3 -, S100 +, SOX10 +, CD68 -
   3. AE1/3 -, PAX8 +, TFE3 +, S100 -, SOX10 - , CD68 -
   4. AE1/3 -, PAX8 -, TFE3 -, S100 + , SOX10 - , CD68 +
   5. AE1/3 -, PAX8 -, TFE3 -, S100 -, SOX10 +, CD68 -

Answers:

Question 1: Correct answer is B
The smears (Figs 1-3) show a cellular specimen with cells arranged in syncytial groups or dispersed as single cells. Dissociated naked rounded nuclei with prominent nucleoli are seen in a delicate thread of metachromatic-staining stromal material. The core biopsy shows polygonal cells with voluminous mostly eosinophilic and rarely vacuolated to cleared cytoplasm in a richly vascularized stroma. Prominent nucleoli and binucleation are identified. Pseudoalveolar pattern is hard to appreciate on the core. By immunohistochemical stains, the neoplastic cells are positive for PAX8 and CD10, while negative for AE1/3, EMA, CA9, SOX10, S100, HMB45, Melan-A, SF1, and Hepatocyte. PAS with and without diastase digestion shows diastase resistant PAS-positive cytoplasmic crystals. FISH study for TFE-3 (XP11.23) break apart is positive for atypical unbalanced XP11.23 break apart. Closer imaging study confirms a lesion adjacent to, but not within the kidney. Taken together, the findings are most consistent with an alveolar soft part sarcoma (ASPS).
ASPS, first descried as a separate entity in 1952, is a rare malignant neoplasm primarily affecting the deep soft tissue of the extremities in young adults and the head and neck region in children. It is defined by a specific genetic alteration, der(17)t(X;17)(p11.2;q25) which results in ASPSCR1-TFE3 gene fusion. The peak age incidence is between 15 to 35 years. Despite the slow growth rate of the primary tumor, ASPS frequently metastasizes to the lung and bone, while metastatic involvement to the liver and lymph nodes are unusual. Brain metastasis is a common feature of ASPS, as comparted to other high grade sarcomas.

Question 2: Correct answer is C

ASPS demonstrates a distinctive morphology in most cases with nests of large epithelioid cells displaying an alveolar and dyscohesive appearance. The monomorphic neoplastic cells have abundant granular eosinophilic or clear glycogen-rich cytoplasm and sharp cytoplasmic borders and the stroma has a delicate vasculature. By electron microscopy, the neoplastic cells are poor in desmosomes and are lined by incomplete basement membranes in contact with capillaries. The cytoplasm shows sparse endoplasmic reticulum and rich mitochondria. The well-developed Golgi apparatus is found to be associated with crystalloids or pre-crystallized electron-dense granules. Special stains such as PAS with diastase can highlight crystalloids, rod-like or rhomboid diastase-resistant membrane-bound intracytoplasmic crystalline formations.

Question 3: Correct answer is C

The differential diagnosis of ASPS is broad, due to overlapping morphological features to other lesions and includes metastatic renal cell carcinoma (RCC), adrenal cortical carcinoma, hepatocellular carcinoma, granular cell tumor, paraganglioma, PEComa, and melanoma, among others. Careful morphologic evaluation, together with immunohistochemistry and FISH studies usually leads to the correct diagnosis. However, differentiating between metastatic RCC and ASPS can be challenging. The peak incidence of clear cell RCC is approximately 2 to 4 decades older that the typical ASPS patients, but overlapping age ranges can occur. Both RCC and ASPS can have clear vacuolated or eosinophilic cytoplasm by morphology, be positive for PAX 8 and TFE 3 by immunohistochemistry, and even share similar fusion genes resulting from identical breakpoints. By contrast to ASPS, RCC should be positive for AE1/3 and EMA. PAX-8 and CD10 are also positive in RCC, but are not specific at all. ASPS is negative for other markers including S100, SOX 10, Melan A, CD163 and CD68. Interpretation of immunotains may be tricky on a core biopsy, and radiological correlation to determine if there is a kidney lesion is the key

References:

1. Wakely PE, McDermott JE, Ali SZ, Cytopathology of Alveolar Soft Part Sarcoma, Cytopathology, a report of 10 cases, 2009 Sep, PMID: 19787801
2. Folpe AL, Deyrup AT, Alveolar soft-part sarcoma: a review and update, J Clin Pathol, 2006 Nov, PMID: 17071801
3. Fujiwara T, Nakata E, Kunisada T, Ozaki T, Kawai A, Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study, BMC Cancer, 2022 Aug 15;22(1);891 PMID: 35971085
4. Ogose A, Morita T, Kobayashi H, Otsuka H, Hirata Y, Yoshida S, Brain metastases in musculoskeletal sarcomas, Jpn J Clin Oncol, 1999 May;29(5):245-7 PMID: 10379335