Abstract
Objectives
To evaluate the sonographic features of secondary involvement of skin and subcutaneous tissues by hematologic malignancies.
Methods
A review of the ultrasound and pathology databases yielded 10 cases with 13 skin and subcutaneous tissue lesions secondary to hematologic neoplasms, which were confirmed by pathology. We used ultrasound to assess the number, location, size, depth of involvement, echogenicity, and vascularity of the lesions.
Results
The study involved five male and five female patients, including four leukemia, two multiple myeloma, and four lymphoma patients. The average age was 45 years (17–66 years). Three patients presented with one lesion, four with two lesions, and three with more than two lesions. All the lesions were located in the trunk and extremities. The lesions ranged from 1.2 to 8.3 cm in size. A total of 10 lesions involved subcutaneous fat tissue. A total of 10 lesions displayed hypoechoic foci within a hyperechoic background, and three appeared hypoechoic, and most of them exhibited abundant vascularity (12 of 13 lesions).
Conclusions
Secondary involvement of skin and subcutaneous tissues by hematologic malignancies often present with multiple palpable masses showing the following ultrasound features: (1) subcutaneous fat infiltration, (2) hypoechoic foci with a hyperechoic background, and (3) abundant vascularity.
Keywords: hematologic neoplasms, soft tissue, ultrasound
Skin and subcutaneous soft tissues involved in hematologic neoplasms often present with multiple palpable masses showing the following imaging features: (1) subcutaneous fat infiltration, (2) hypoechoic foci with a hyperechoic background, and (3) abundant vascularity.
1. INTRODUCTION
Hematologic neoplasms are tumors in the blood and blood‐forming tissue (the bone marrow and lymphatic tissue), including leukemia, lymphoma, and multiple myeloma, accounting for about 9% of all neoplasms. 1 Hematologic neoplasms can involve the skin as a site of secondary involvement. Cutaneous manifestations of hematologic neoplasms can be divided into specific and non‐specific. 2 Specific cutaneous manifestations, infiltrated with malignant hematopoietic cells in the skin, and subcutis, are detected in 15.1% of cases. 3 Non‐specific cutaneous manifestations include paraneoplastic syndromes, drug reactions, opportunistic infections, and other conditions related to myelosuppression. Specific cutaneous infiltration in patients with hematologic neoplasms suggests a poor prognosis. 3 The reported median survival time for patients with cutaneous involvement varied from 4.5 to 12.0 months among the published series. 4 , 5 , 6 The mortality rate in patients with specific cutaneous manifestations was 18.2%, compared to 4.1% in patients without these lesions. 3 Therefore, specific cutaneous manifestations are crucial indications in determining disease staging and prognosis.
The diagnosis of cutaneous involvement is mainly based on skin morphology and confirmed by skin biopsy. 7 , 8 Nodules, plaques, papulo‐nodular, and papules are four predominant morphologies of specific cutaneous manifestations found in patients with hematologic neoplasms. 7 The infiltrated locations may include epidermis, dermis, or hypodermis. In previous works of literature, studies of specific cutaneous infiltration of hematologic neoplasms were primarily focused on skin morphology. A few papers described skin and subcutaneous tissue imaging characteristics involved in hematologic neoplasms. In the study by Lee et al., CT and MRI findings of superficial soft tissue lymphomas were non‐specific. 9 To our knowledge, no systematic review has been done for ultrasound findings of skin and subcutaneous tissue involvement in hematologic neoplasms. With high accessibility and excellent spatial resolution, ultrasound has become an ideal modality for examining skin, and subcutaneous tissue. 10
We, therefore, sought to describe and systematically analyze the ultrasound findings of 10 patients with skin and subcutaneous tissue involvement in hematologic neoplasms.
2. PATIENTS AND METHODS
2.1. Patients
Our hospital institutional review board approved this retrospective study, waiving informed consent. We reviewed ultrasound and pathology databases to diagnose patients with hematologic neoplasms. We analyzed the ultrasound findings of 10 patients diagnosed with secondary cutaneous involvement of systemic hematologic neoplasms between January 2017 and July 2021. All patients underwent ultrasound examination, because of superficial palpable masses or infiltrated skin lesions, before needle biopsy or surgical resection. A total of 13 lesions were confirmed as skin and subcutaneous tissue involvement by pathology. The lesions were biopsied or surgically removed 1–11 days after ultrasound examination (mean 3 days). Clinical data were obtained by reviewing electronic medical records and from follow‐up information provided by the patients' physicians. The clinical data included types of primary tumor, time for skin involvement after diagnosis, survival time after skin involvement, and cutaneous manifestations.
2.2. Sonographic examinations and image analysis
Two musculoskeletal sonologists with over 5 years of experience analyzed the ultrasound images. Ultrasound systems used for the study were as follows: SuperSonic Aixplorer ultrasound system (SuperSonic Imagine) with a 15–4 MHz high‐frequency linear array; Mindray Resona7 ultrasound system (Mindray) with a 14–5 MHz high‐frequency linear array; Aplio 500 ultrasound system (Toshiba Medical Systems) with a 14–5 MHz high‐frequency linear array. Two sonologists reviewed all available ultrasound images and decided on all interpretations based on consensus. If not, a third sonologist was involved.
The following sonographic features of skin and subcutaneous tissue involvement in hematologic neoplasms were evaluated: (1) Number of lesions; (2) Location in the body; (3) Size, including peripheral hyperechoic region of the lesion, measured using the longest diameter in the largest plane. (4) Depth of involvement as follows: (i) skin (dermis and epidermis), (ii) subcutaneous fat, and (iii) muscle involvement. If the lesion involved both skin and subcutaneous fat, it was labeled as (i) + (ii). (5) Echogenicity, evaluated comparing the lesion with the echogenicity of adjacent tissue. (6) Vascularity. The vascularity of the lesions on color Doppler sonography was assessed according to Adler grade classifications and classified into four levels. 11 Grade 0–1 indicated low vascularity, while grade 2–3 indicated high vascularity. The color scale was adjusted to 3–8 cm/sec, and the color Doppler gain was set just below the color noise threshold to visualize the low‐velocity flow.
3. RESULTS
3.1. Clinical findings
Patients' demographic information and clinical features were shown in Table 1. The average age of the 10 patients was 45 years (range, 17–66 years), including four leukemia, two multiple myeloma and four lymphoma patients. Nine patients developed skin and subcutaneous tissue lesions within 3–84 months after the onset of hematologic neoplasms, and one patient started simultaneously (mean time 24.9 months). The median survival time was 13.5 months after skin involvement (8–36 months). Nodules were found in all patients. Two patients had multiple papules and plaques in the trunk and extremities simultaneously.
TABLE 1.
Demographic data and sonographic findings for all patients
| No. | Sex | Age (year) | Primary tumor | Time to skin involvement after diagnosis (month) | Overall survival since skin involvement (month) | Cutaneous manifestations | Number of Lesions | location in the body | Size (mm) | Depth of involvement a | Echogenicity b | Vascularity |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | M | 42 | IgG MM | 84 | 12 | Nodular | 2 | Abdominal wall | 83 | (3) | (1) | Abundant |
| Abdominal wall | 23 | (2) | (1) | Abundant | ||||||||
| 2 | M | 66 | IgD MM | 29 | 8 | Nodular | 2 | Lower back | 20 | (2) | (1) | Abundant |
| Lower back | 22 | (2) | (1) | Abundant | ||||||||
| 3 | F | 43 | AML | 0 | 10 | Papule, plaque, nodular | 1 | Lower back | 35 | (2) | (1) | Abundant |
| 4 | F | 27 | ALL | 18 | 15 | Nodular | 2 | Left thigh | 17 | (1) | (2) | Abundant |
| Right thigh | 22 | (1) | (2) | Abundant | ||||||||
| 5 | M | 65 | AML | 16 | 12 | Papule, plaque, nodular | 1 | Left forearm | 65 | (1) + (2) | (1) | Abundant |
| 6 | M | 41 | AML | 3 | 15 | Nodular | Numerous | Right thigh | 12 | (2) | (1) | Abundant |
| 7 | F | 66 | T‐NHL | 12 | 10 | Nodular | Numerous | Right upper arm | 52 | (2) | (1) | Abundant |
| 8 | M | 38 | B‐NHL | 48 | 16 | Nodular | Numerous | Chest wall | 17 | (1) + (2) | (1) | Minimal |
| 9 | F | 17 | T‐NHL | 24 | 22 | Nodular | 1 | Abdominal wall | 30 | (1) + (2) | (2) | Abundant |
| 10 | F | 45 | B‐NHL | 15 | 36 | Nodular | 2 | Left foot | 20 | (1) + (2) | (1) | Abundant |
Abbreviations: ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; B‐NHL, B‐cell non‐Hodgkin lymphomas; F, female; IgD MM, immunoglobulin D multiple myeloma; IgG MM, immunoglobulin G multiple myeloma; M, male; T‐NHL, T‐cell non‐Hodgkin lymphomas.
(1) Skin involvement; (2) Subcutaneous fat involvement; (3) Muscle involvement.
(1) Hypoechoic foci within a hyperechoic background; (2) Hypoechoic.
3.2. Ultrasound findings
We summarized the sonographic findings of all patients in Table 1. Three patients presented with one lesion, four with two lesions, and three with more than two lesions. Seven lesions were located in the trunk, involving the abdominal wall, chest wall, or lower back. The other lesions were found in the extremities, including thigh, forearm, upper arm, and foot. The lesions ranged from 1.2 to 8.3 cm in size. The lesions occurred in the skin and subcutaneous fat layer (four patients), subcutaneous fat layer (four patients), muscular layer, and subcutaneous fat layer (one patient), and skin (one patient). A total of 10 lesions involved subcutaneous fat tissue. A total of 10 lesions showed hypoechoic foci with a hyperechoic background (Figures 1 and 2), and the other three lesions appeared hypoechoic (Figure 3). Vascularity was minimal in 1 lesion and abundant in 12 lesions.
FIGURE 1.
Leukemia involving the lower back in a 43‐year‐old woman (case 3): (A) Sonogram shows hypoechoic foci within a hyperechoic background on the lower back. (B) Color Doppler sonogram shows abundant vascularity. (C, D) Biopsy specimen (hematoxylin–eosin, original magnification 100, 400) of areas dominated by hyperechoic echogenicity shows that lymphoid cells cluster in a background of adipocytes.
FIGURE 2.
Multiple myeloma involving the lower back in a 66‐year‐old man(case 2): (A) Sonogram shows hypoechoic foci within a hyperechoic background on the lower back. (B) Color Doppler sonogram shows abundant vascularity. (C, D) Biopsy specimen (hematoxylin–eosin, original magnification 100, 400) of the areas predominantly hypoechoic echogenicity appears as dense plasmacytoid cells cluster.
FIGURE 3.
Leukemia involving the right thigh in an 27‐year‐old woman (case 4): (A) Sonogram shows a hypoechoic mass mainly located in the dermis. (B) Color Doppler sonogram shows abundant vascularity. (C, D) Biopsy specimen (hematoxylin–eosin, original magnification 50, 400) shows the areas of lower echogenic feature where B‐lymphoblastic cells are more densely distributed. (E, F) The immunohistochemical staining for CD20, CD34, Ki‐67, and TDT show that cellular infiltrates contain large numbers of CD34+ and TDT+ (×50).
3.3. Comparison of ultrasound and histopathologic findings
In this study, we additionally assessed the histopathologic components. Biopsied areas dominated by hyperechoic showed that tumor cells clustered in a background of adipocytes (Figure 1), While areas predominantly hypoechoic echogenicity appeared as dense tumor cells clustered (Figure 2). Similarly, areas where the tumor cells were more densely distributed showed lower echogenic features (Figure 3).
4. DISCUSSION
Hematologic neoplasms can present as specific secondary cutaneous lesions. Patients were first diagnosed with systemic hematologic neoplasms in most cases and may subsequently develop cutaneous neoplasms. The findings in our study were remarkable for the high percentage of cases presenting as nodular (100%). Two patients had papules and plaques along with nodules. In the study by Rebeca et al. 8 nodules (36.7%) were the predominant findings in patients with hematological neoplasms, followed by plaques (18.4%), papulo‐nodular (12.2%), and papules (12.2%). The selection of patients in our study may be biased, as it was limited to the condition that patients' lesions were palpable, potentially inaccurately showing the true incidence of cutaneous manifestation. In our study, most patients presented with multiple lesions (≥2) of skin and subcutaneous tissue, consistent with the previous research. 8
We evaluated the sonographic findings and found 10 lesions containing hypoechoic foci within a hyperechoic background, and the other three lesions appeared hypoechoic. Hypoechoic foci within a hyperechoic background were similar to the ultrasonic performance of segmental panniculitis. 12 There were few case reports describing ultrasound imaging findings of subcutaneous lesions infiltrated by hematologic neoplasms. 13 , 14 , 15 , 16 On ultrasound, the lesions within the subcutaneous fat layer appeared as linear hypoechoic areas within diffuse hyperechogenicity (i.e., panniculitis‐like echo texture). 13 The hyperechoic background may be due to tumor cell infiltration in the subcutaneous fat layer, which increased the number of reflecting interfaces. Local aggregation of tumor cells which had similar size and shape, resulted in reduced acoustic impedance, and appeared hypoechoic. In the study by Chiou et al. 11 of 12 cases in primary peripheral soft tissue lymphoma showed relatively homogeneous hypoechogenicity. The area of lymphocyte proliferation had less interface density than was needed to reflect the sound beam, which resulted in hypoechogenicity. 17 However, in our study, only one of the four subcutaneous tissue lesions secondary to lymphoma was hypoechoic, while the rest contained hypoechoic foci within a hyperechoic background.
Our color Doppler images showed 12 masses with abundant vascularity, and one mass with minimal vascularity, which was concordant with primary peripheral soft tissue lymphoma in the previous research. 17
There are several limitations to this study. First, the small sample size limited the evaluation of more useful ultrasound imaging features. Second, when patients had multiple lesions, not all the lesions were confirmed by pathology. Finally, further comparison study is needed between soft tissue infiltrated by hematologic neoplasms and other skin and subcutaneous tissue disorders such as panniculitis.
In conclusion, secondary involvement of skin and subcutaneous tissues by hematologic malignancies often present with multiple palpable masses showing the following ultrasound features: (1) subcutaneous fat infiltration, (2) hypoechoic foci with a hyperechoic background, and (3) abundant vascularity.
FUNDING INFORMATION
The Science Technology and Innovation Commission of Shenzhen Municipality in China (grant no. JCYJ 20210324110015040), The Shenzhen Key Medical Discipline Construction Fund (grant no. SZXK051), Financial Support of The Guangdong High‐level Hospital Construction Fund (grant no. GD2019260), and The Shenzhen Virtual Reality Clinical Application Public Service Platform Promotion Project (grant no. XMHT20190104001).
CONFLICT OF INTEREST
The authors declare no conflicts of interest.
Lyu H, Chen XM, Yu GY, et al. Sonographic features of secondary involvement of skin and subcutaneous tissues by hematologic malignancies. J Clin Ultrasound. 2022;50(9):1436‐1442. doi: 10.1002/jcu.23368
Funding information The Science Technology and Innovation Commission of Shenzhen Municipality in China, Grant/Award Number: JCYJ 20210324110015040; The Shenzhen Key Medical Discipline Construction Fund, Grant/Award Number: SZXK051; The Guangdong High‐level Hospital Construction Fund, Grant/Award Number: GD2019260; The Shenzhen Virtual Reality Clinical Application Public Service Platform Promotion Project, Grant/Award Number: XMHT20190104001
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.