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Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 385-388

Finding unusual pathology in usual clinical presentation: Huge implications for therapy


1 Department of Medical Oncology, Tata Memorial Center, Varanasi, Uttar Pradesh, India
2 Department of Medical Pathology, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malviya Cancer Center, Tata Memorial Center, Varanasi, Uttar Pradesh, India

Date of Submission08-Apr-2021
Date of Decision30-Apr-2021
Date of Acceptance22-May-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Akhil Kapoor
Department of Medical Oncology, Homi Bhabha Cancer Hospital and Mahamana Pandit Madan Mohan Malviya Cancer Center, Tata Memorial Center, Varanasi, Uttar Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/crst.crst_68_21

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How to cite this article:
Roy S, Dhal I, Kapoor A. Finding unusual pathology in usual clinical presentation: Huge implications for therapy. Cancer Res Stat Treat 2021;4:385-8

How to cite this URL:
Roy S, Dhal I, Kapoor A. Finding unusual pathology in usual clinical presentation: Huge implications for therapy. Cancer Res Stat Treat [serial online] 2021 [cited 2021 Jul 24];4:385-8. Available from: https://www.crstonline.com/text.asp?2021/4/2/385/320220




  Case Vignette 1 Top


A 24-year-old male without any comorbidities presented to our hospital with a 4-month history of progressively increasing hoarseness of voice with occasional shortness of breath. An indirect laryngoscopic examination revealed an ulceroproliferative mass arising from the right false vocal cord into the ventricle of the larynx and extending up to the vallecula. Movements of the true vocal cords were normal. There was no cervical lymphadenopathy. The baseline routine blood parameters were within the normal limits. A positron emission tomography (PET) contrast-enhanced computed tomography (CECT) revealed 18F-fluorodeoxyglucose uptake in the larynx with no evidence of distant metastases [Figure 1].
Figure 1: Positron emission tomography contrast-enhanced computed tomography image showing intense uptake of 18F-fluorodeoxyglucose in the larynx

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A direct laryngoscopic biopsy was performed, and the histopathological examination was suggestive of a small round cell tumor. The patient underwent partial laryngectomy at another hospital, and the final histopathological review revealed a tumor composed of sheets and vague lobules comprising uniform neoplastic cells partially separated by delicate fibrovascular septae. The individual cells showed round nuclei with fine chromatin and scant cytoplasm, and areas of necrosis and hemorrhage were present [Figure 2]. What is the diagnosis, and what should be done next? Once you have finalized your answer, turn to the next page to read on.
Figure 2: (a) Microsection showing overlying laryngeal mucosa in the upper right region and submucosa with sheets of small round cells (H and E, ×40). (b-f) Higher magnification showing small round cells with scant cytoplasm and coarse chromatin (H and E, ×400)

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  Case Vignette 2 Top


An 18-year-old girl presented to our hospital with a 2-month history of a progressively growing mass in the right breast. Physical examination revealed an ulceroproliferative lesion of size 5.5 cm × 4.2 cm in the upper outer quadrant of the right breast with overlying skin thickening without any axillary and supraclavicular lymphadenopathy. There was no palpable lump underlying the lesion, and the nipple-areolar complex was normal. There was no fixity of the lesion to the underlying pectoralis muscles or the chest wall. No obvious abnormality was observed on palpation of the other breast, and the systemic examination was normal.

Her routine blood parameters were within the normal limits, and a CECT scan revealed an irregular heterogeneous mass of size 6.1 cm × 4.4 cm in the right breast with overlying skin thickening. A solitary right axillary node measuring 11 mm × 5 mm with a 6-mm right internal mammary node was seen without any other abnormalities. There was no visceral or bone metastasis. A histopathological examination of the core biopsy specimen revealed sheets of malignant round cells [Figure 3]a. Higher magnification showed tumor cells arranged in sheets and forming rosettes [Figure 3]b.
Figure 3: (a) Microsection showing normal breast tissue on the upper side and sheets of malignant round cells at the lower end (H and E, ×40). (b) Higher magnification showing tumor cells arranged in sheets and forming rosettes (in the center) (H and E, ×400)

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What is the diagnosis, and what should be done next? Once you have finalized your answer, read on.

Further investigations to confirm the diagnosis and treatment

In Case 1, the differential diagnoses included extraskeletal Ewing sarcoma, synovial sarcoma, and non-Hodgkin lymphoma. Immunohistochemistry (IHC) revealed diffuse membranous positivity for CD99, and the cells also stained positive for FLI1; however, they were pan-cytokeratin and leukocyte common antigen negative, thus suggesting Ewing sarcoma/peripheral neuroectodermal tumor [Figure 4]. After surgery, the patient was planned to receive adjuvant radiation to a total dose of up to 50 Gy, 2 Gy per fraction, 5 days a week, concurrent with weekly vincristine. The patient tolerated chemoradiation well, after which he was started on maintenance chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) alternating with ifosfamide and etoposide (IE) for a duration of 1 year. The patient is doing well at 4 months of follow-up post completion of treatment.
Figure 4: (a) Overlying mucosa is positive for pan-cytokeratin, while the tumor cells are pan-cytokeratin-negative; (b) CD45-negative tumor cells, (c) CD-99 shows diffuse, strong, membranous positivity, (d) FLI-1-positive tumor cells

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In Case 2, IHC showed diffuse membranous positivity for CD99 along with positive staining for FLI1. In addition, the tumor cells were negative for CD45 and GATA3, thus confirming the diagnosis of extraskeletal Ewing sarcoma [Figure 5].
Figure 5: (a) CD99 showed diffuse membranous positivity. (b) Tumor cells were positive for FLI-1, (c) GATA3 was negative in all the cells

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The patient received neoadjuvant chemotherapy with VAC alternating with IE for six cycles, and a post-therapy PET CT scan showed partial response. She underwent right breast-conserving surgery along with axillary dissection. A histopathological examination showed pathological complete response. She was continued on the similar maintenance chemotherapy protocol of Ewing sarcoma and also received locoregional radiotherapy. At 6-month follow-up postcompletion of treatment, she remains disease-free.


  Discussion Top


Peripheral neuroectodemal tumors (PNET) constitute a group of malignant tumors comprising small, round cells that arise from the neuroectodermal elements of the migrating embryonic cells derived from the neural crest.[1] Primary Ewing sarcomas are more common in the bony elements of young adults and adolescents. Extraosseous Ewing sarcoma is a member of the PNET family that has a tendency to develop in the truncal and axial soft tissues, e.g., the chest wall PNET, also known as the Askin tumor. Other unusual sites of development include the paravertebral region and extremities and rarely in the kidney, ureter, bladder, pancreas, ovary, lungs, parotid gland, testis, and seminal vesicles.[2],[3] Extraosseous Ewing sarcoma of the breast and larynx are extremely rare entities. Around 13 cases of extraosseous Ewing sarcoma of the breast and 5 cases of laryngeal PNET have been reported so far in the literature. Here, we share our experience with the clinical presentation, diagnosis, and treatment of one case each of laryngeal and breast PNET.

Extraosseus Ewing sarcoma of the breast and larynx usually develop at an early age and show aggressive clinical behavior. This group of tumors is typically characterized by CD99 antigen (also known as MIC2), vimentin, S-100, and neuron-specific enolase expression on IHC.[4] The chromosomal translocation (11;22) (q24;q12) is seen in more than 90% of patients with PNET, although other rare translocations have also been reported. This translocation results in the fusion of the EWS gene on chromosome 22 with the FLI1 gene on chromosome 11, resulting in the EWS-FLI1 fusion protein. Cytogenetic analysis by FISH is the method of choice to confirm the presence of this translocation, and EWS-FLI1 fusion by RT-PCR methods helps to differentiate Ewing sarcoma from other round cell tumors; however, this was not feasible in our patients due to logistic constraints. In addition, IHC using the antibody against the FLI1 protein can also help in the detection of this fusion product. [Table 1] and [Table 2] provide a summary of the cases of laryngeal and breast PNET reported so far in the literature.
Table 1: Review of the reported cases of extraskeletal Ewing's sarcoma of the larynx and the present case

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Table 2: Review of the reported cases of extraskeletal Ewing sarcoma of the breast and the present case

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Like PNETs arising in other anatomical locations, extraosseous Ewing sarcoma of the breast and larynx are treated using trimodality therapy consisting of surgery, radiotherapy, and chemotherapy. The current standard of care is neoadjuvant chemotherapy followed by surgery and/or radiation followed by adjuvant chemotherapy. The recommended chemotherapy protocol is VAC alternating with IE for a total duration of 1 year.[23] Local therapy in case of breast PNET involves either modified radical mastectomy or breast-conservation surgery followed by adjuvant radiation, whereas, in laryngeal PNET, therapy includes either laryngectomy with an adequate margin, if feasible, or radical radiotherapy. Adjuvant radiation after definitive surgery is indicated in cases with a positive margin.

The limitations of our case series are the short duration of follow-up and the fact that we were unable to perform a cytogenetic and molecular analysis of the tumor. However, in the perspective of the reported literature, our cases responded and tolerated the multimodality treatment well, thus providing some guidance for the management of other similar rare tumor presentations. To conclude, more prospective research is needed to optimize the treatment and improve the survival outcomes in rare cases of PNET.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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[PUBMED]  [Full text]  
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2]



 

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