Cytodiagnosis of scalp swelling: An uncommon presentation of a common neoplasm

CLINICAL HISTORY

A 56-year-old male presented with complaint of swellings on the scalp for a month. On examination, two swellings were identified in the left parietal and the occipital region, measuring 5 × 4 cm and 3 × 3 cm, respectively. The contrast-enhanced computed tomography scan revealed soft-tissue densities in relation to the calvarium, with underlying bone erosion and intracranial extension [Figure 1c]. Smears from the fine-needle aspirate cytology (FNAC) procedure performed are shown [Figure 1a and b].

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Figure 1:

(a) Fine-needle aspirate cytology smear shows numerous mature plasma cells, few immature form, lymphocytes, and bare nuclei (MGG stain, ×400). (b) Flame cell (MGG stain, ×1000). (c) Axial cranial CT reveals osteolytic extradural soft-tissue masses (arrowhead) involving the diploe of the calvarium, with cortical defects and intracranial extension.

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QUESTION

What is your interpretation?

1. Plasma cell granuloma

2. Non-Hodgkin’s lymphoma

3. Plasmacytoma

4. Syringocystadenoma papilliferum

Answer

The correct cytopathological interpretation is:

(c) Plasmacytoma

The cytology smears show a dispersed population of cells having round, eccentric nucleus, with coarsely clumped chromatin, inconspicuous nucleolus, and dense cytoplasm with perinuclear hof, conforming to the morphology of mature plasma cells [Figure 1a]. Also observed were immature plasma cells having a single large nucleus and prominent nucleolus. Apart from these, binucleate, multinucleate forms, and flame cells were noteworthy [Figure 1b].

Non-neoplastic proliferation of plasma cells is usually seen in association with mixed inflammatory cells such as lymphocytes and neutrophils. Plasma cell granuloma, also known as inflammatory pseudotumor, is a fibroblastic/ myofibroblastic lesion cytologically characterized by the presence of spindle cells accompanied by an inflammatory infiltrate of numerous plasma cells, lymphocytes, and few eosinophils. Although rare in soft tissue, it has been reported most commonly in lungs, oral cavity, gingival mucosa, etc.

Some non-Hodgkin lymphomas, in particular, high-grade malignant immunoblastic lymphoma and marginal zone B-cell lymphoma may depict plasmacytoid morphology, posing a morphological dilemma. However, possibility of non-Hodgkin’s lymphoma is excluded by a characteristic absence of lymphoglandular bodies in the background.

Some cutaneous adnexal tumors, such as syringocystadenoma papilliferum, show numerous plasma cells on FNA smears. This entity is superficial, limited to the skin, and presents clinically as a nodular, warty tumor or as ulcerated lesion of the scalp, neck, and face. In addition to the plasma cells, the smears also show cohesive aggregates of epithelial cells, with focal papillary configuration.

FOLLOW-UP OF THE PRESENT CASE

Further investigations revealed mild anemia (Hb 8.7 g/dL), hypercalcemia (11.3 mg/dL), and deranged renal function (creatinine 11 mg/dL and urea 45 mg/dL). Bone marrow (BM) aspiration and trephine biopsy showed the presence of 17% plasma cells [Figure 2a-c]. Plasma protein electrophoresis revealed a prominent “M band” in the gamma globulin region [Figure 2d]. Unfortunately, the disease had an aggressive course, and the patient subsequently expired before a therapeutic intervention could be attempted.

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Figure 2:

(a) Bone marrow aspirate smear shows aggregates of plasma cells showing eccentrically placed nucleus and cytoplasmic perinuclear hof (MGG stain, ×400). (b) A giant binucleate myeloma cell showing coarse nuclear chromatin and prominent nucleoli. A mature plasma cell is seen in the background (MGG stain, ×400). (c) Bone marrow biopsy shows increased plasma cells, seen as singly scattered cells (H and E, ×400). (d) Serum electrophoresis shows a prominent M band in the gamma globulin region (arrowhead).

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ADDITIONAL QUIZ QUESTIONS

Q1. What is your final diagnosis after cytological and hematological, biochemical, and serological evaluation [Figure 2]?

1. Solitary bone plasmacytoma

2. Solitary extramedullary plasmacytoma

3. Solitary plasmacytoma with minimal marrow involvement

4. Multiple myeloma

Q2. Which of the following is not considered a myeloma defining event in patients without CRAB features? (Hypercalcemia [C], renal impairment [R], anemia [A], and bone lesions [B])

1. BM plasma cells ≥60%

2. Monoclonal globulin spike on serum protein electrophoresis, with an immunoglobulin (Ig) G peak of >3.5 g/dL or an IgA peak of >2 g/dL, or urine protein electrophoresis (in the presence of amyloidosis) result of greater than 1 g/24 h

3. Abnormal MRI with more than 1 focal lesion, with each lesion being >5 mm in size

4. Involved/uninvolved serum free light chain ratio ≥100

Q3. Which of the following cytogenetic abnormality is most commonly associated with extramedullary manifestations in multiple myeloma?

1. del(17p13)

2. t(4;14)

3. t(13;14)

4. t(14;16)

Answers to the additional quiz questions

1 (d); 2 (b); 3 (a)

1. (d). Solitary plasmacytoma is defined by the presence of a single biopsy-proven lesion (either bony or extramedullary) and a normal BM examination.^[1] Extramedullary plasmacytoma (EMP) is a plasma cell neoplasm of soft tissue without BM involvement or other systemic characteristics of multiple myeloma. Patients with solitary plasmacytoma who have limited (<10%) clonal BM plasma cells are considered to have solitary plasmacytoma with minimal marrow involvement.^[1] The present case shows 17% plasma cells in the BM. Hence, a diagnosis of multiple myeloma (MM) is appropriate.

2. (b). The International Myeloma Working Group updated the criteria for diagnosis MM to allow, in addition to the classic CRAB features, three “myeloma-defining biomarkers.” The new definition of MM is:^[1]

   Clonal BM plasma cells >10% or biopsy-proven bony or EMP in addition to any one or more of the CRAB features and myeloma-defining events:

   • Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically

     • Hypercalcemia: Serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11 mg/dL)

     • Renal insufficiency: Creatinine clearance <40 mL per minute or serum creatinine >177 mol/L (>2 mg/dL)

     • Anemia: Hemoglobin value of >20 g/L below the lowest limit of normal or a hemoglobin value <100 g/L

     • Bone lesions: One or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If BW has <10% clonal plasma cells, more than 1 bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement

   • Any one or more of the three biomarkers of malignancy or myeloma defining events

     • 60% or greater clonal BM plasma cells

     • Serum involved/uninvolved free light chain ratio of 100 or greater (provided the absolute level of the involved light chain is at least 100 mg/L)

     • More than 1 focal lesion on MRI that is at least 5 mm or greater in size.^[1]

3. (a). MM with extramedullary involvement appears to be an uncommon phenomenon. Studies have shown extramedullary manifestations in MM to confer higher incidence of poor cytogenetic aberrations and resistance to novel therapeutic agents. These patients are known to show higher incidence of del(17p13) and amp(1q21) and pose potential therapeutic difficulties.^[2]

BRIEF REVIEW OF THE TOPIC

MM is one of the most frequently encountered hematological malignancies, occurring as a result of uncontrolled expansion of clonal plasma cells.^[1] It is a multifocal neoplasm, with presenting complaints of anemia, infections, hypercalcemia, renal failure, neurological manifestations, punched out lytic lesions of bone, and osteoporosis. However, occasionally, it may present with extramedullary manifestations in the form of tumor masses in the bone, soft tissue, or viscera. EMP has an incidence of 6–8% at the time of diagnosis of MM.^[3] The EMP is found most commonly in the head-and-neck region (80%), especially the nasopharynx and paranasal sinuses and to a lesser extent in the gastrointestinal tract, central nervous system, lymph nodes, etc.^[4] MM presenting as localized soft-tissue swelling in the scalp, with intracranial extension is rare, with few cases published so far.^[4-7]

A pathologically diagnosed plasmacytoma of the soft tissue may be the only presentation of MM in the initial phase or can be a late extramedullary manifestation seen in the aggressive phase of the disease. It can also be a direct extension or metastasis from underlying solitary plasmacytoma of the bone. The case discussed here, probably arose from the plasmacytoma of the underlying calvarium, with the mass causing bony erosion, cortical breach, and extension into the overlying soft tissue of the scalp.

Literature discussing utilizing cytology for the diagnosis of EMP is further limited.^[8-10] Depending on the site of the EMP, different types of cytological specimen may be obtained. FNAC is usually the first line of investigation for any palpable swelling such as EMP of soft tissue and lymph nodes. Rarely, lesions may also present in lung and gastrointestinal tract, where a guided FNA from the mass, scrape smears, bronchoscopic, or endoscopy-guided brushings may be useful.^[10] The case discussed here illustrated the classical morphology of malignant plasma cells on FNAC smears. The diagnosis is usually straightforward in the presence of numerous mature plasma cells, with limited differentials. Nevertheless, the cells may occasionally show marked anaplasia and pleomorphism, accompanied by giant myeloma cells posing a cytological diagnostic dilemma. The larger cells with a centrally placed nucleus, prominent nucleoli, and sometimes associated with multinucleation may be misinterpreted as Reed-Sternberg cells or as megakaryocytes.^[8-10] The plasmablastic morphology may further be confused with atypical lymphoid cells, immunoblasts, and centroblasts seen in high-grade nonHodgkin’s lymphoma. However, the presence of at least few mature plasma and a characteristic lack of lymphoglandular bodies in the background act as diagnostic clues to plasmacytoma. The EMP also needs to be distinguished from other extranodal marginal B-cell lymphomas and MALTomas with plasmacytic differentiation. Furthermore, site-specific differentials may be considered at varied locations. For example, in FNAC from neuroendocrine tumor of the liver, spleen, and pancreas, differentiating tumor cells from plasma cells are a challenge. In breast, plasmacytoma may be mistaken as lobular carcinoma to the unsuspecting eyes. Immunohistochemistry on cell block preparation and flow cytometry of the aspirated fluid provides a valuable adjunct in these scenarios. The diagnosis is further simplified when protein electrophoresis, BM evaluation, and skeletal survey are evaluated.^[9]

Differentiating solitary plasmacytoma from a case of MM is of paramount importance, as the therapeutic approach and prognosis differ. The prognosis of plasmacytoma concurrent with newly diagnosed MM is dismal, with a median survival of less than 3 years.^[11] It may further indicate failure to respond in cases already on therapy. Studies have shown a satisfactory role of surgical removal of the tumor in combination with post-operative radiotherapy and chemotherapy for systemic involvement.^[4,6]

SUMMARY

The present case describes the rare presentation of MM as scalp swellings. FNAC is a simple, first-line investigation for the diagnosis of extramedullary manifestation of MM, which helps in the early diagnosis and management of these patients.